Skincare

Humectant
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A humectant /hjuːˈmɛktənt/ is a hygroscopic substance used to keep things
moist. They are used in many products, including food, cosmetics, medicines
and pesticides. When used as a food additive, a humectant has the effect of
keeping moisture in the food. Humectants are sometimes used as a
component of antistatic coatings for plastics.
A humectant attracts and retains the moisture in the air nearby via
absorption, drawing the water vapor into or beneath the organism's or
object's surface. This is the opposite use of a hygroscopic material where it is
used as a desiccant used to draw moisture away.
In pharmaceuticals and cosmetics, humectants can be used in topical dosage
forms to increase the solubility of a chemical compound's active ingredients,
increasing the active ingredients' ability to penetrate skin, or its activity time.
This hydrating property can also be needed to counteract a dehydrating
active ingredient (e.g., soaps, corticoids, and some alcohols), which is why
humectants are common ingredients in a wide range of cosmetic and personal
care products that make moisturization claims (e.g., hair conditioners, body
lotions, face or body cleansers, lip balms, and eye creams).
Chemistry
A humectant is often a molecule with several hydrophilic groups, most often
hydroxyl groups; however, amines and carboxyl groups, sometimes esterified,
can be encountered as well (its affinity to form hydrogen bonds with
molecules of water is the crucial trait).
Examples
Examples of some humectants include:
Propylene glycol, hexylene glycol, and butylene glycol

Aloe vera gel
Alpha hydroxy acids such as lactic acid
Egg yolk and egg white
Glyceryl triacetate
Honey
Lithium chloride
Molasses
Polymeric polyols such as polydextrose
Quillaia
Sodium hexametaphosphate E452i
Sugar alcohols (sugar polyols) such as glycerol, sorbitol, xylitol, maltitol
Urea
Castor oil
Uses
A humectant is a substance that is used to keep products moisturized and
affects the preservation of items, which can be used in cosmetic products,
food and tobacco. A humectant-rich formulation contains simple alcoholic
sugar that can increase skin hydration and helps to remove and reduce
thickness of skin.
Food additives
Some common humectants used in food are honey and glucose syrup both
for their water absorption and sweet flavor. Glucose syrup also helps to retain
the shape of the product better than other alternatives, for a longer period of
time. In addition, some humectants are recognized in different countries as
good food additives because of the increase in nutritional value that they
provide, such as sodium hexametaphosphate.
In order to gauge a compound's humectancy, scientists will put it through a
series of tests, often involving water absorption. In tests involving toothpaste,
the process is also coupled with a sweetness test and a crystallization test.
When humectancy is being assessed in different products, testers will
compare the results to other humectants that are already used in those
products, in order to evaluate efficiency.
Some of these humectants are seen in non-ionic polyols like sucrose, glycerin
or glycerol and its triester (triacetin). These humectant food additives are
used for the purpose of controlling viscosity and texture. Humectants also add
bulk, retain moisture, reduce water activity, and improve softness. A main
advantage of humectant food additives is that, since they are non-ionic, they
are not expected to influence any variation of the pH aqueous systems.
Glycerol or glycerin humectants undergo a pretreatment process using
saponification, bleaching, ion exchange exclusion, both cationic and ionic ion
exchanges, vacuum flash evaporation, thin film distillation, and heating to
produce a 100% pure glycerol.
Humectants are used in stabilization of food products and lengthening shelf
life through food and moisture control. The available moisture determines
microbial activity, physical properties, sensory properties and the rate of
chemical changes, that if not controlled, are the cause of reduced shelf life.
Examples are dry cereal with semi-moist raisins, ice cream in a cone,
chocolate, hard candy with liquid centers and cheese. Humectants are used to
stabilize the moisture content of foodstuffs and are incorporated as food
additives. Humectants are also used in military technology for the use of
MREs and other military rations. A number of food items always need to be
moist. The use of humectants reduces the available water, thus reducing
bacterial activity. They are used for safety issues, for quality, and to have a
longer shelf-life in food products.
An example of where humectants are used to keep food moist is in products
like toothpaste as well as certain kinds of cookies. Regional kinds of cookies
often use humectants as a binding agent in order to keep moisture locked
into the center of the cookie rather than have it evaporate out. Humectants
are favored in food products because of their ability to keep consumable
goods moist and increase shelf-life.
Cosmetics
Humectants are frequently used in cosmetics as a way of increasing and
maintaining moisture in the skin and hair, in products including shampoo,
conditioner, frizz serum, lotions, creams, lip treatments, cleansers, after-sun
lotion, and some soaps or body lotions. As hygroscopic moisturizers,
humectants work by attracting water to the upper layer of the skin (stratum
corneum). All humectants have common hydroxyl groups which allow them to
participate in hydrogen bonding and attract water. This process attracts
moisture from the outer layer of the skin or, in high humidity, from the
atmosphere. The moisture is then trapped against the epidermis or the shaft
of the hair, depending on where the humectant is applied. Various
humectants have different ways of behaving because they differ in water
binding capacity at different humidities.
Humectants used in cosmetics include triethylene glycol, tripropylene glycol,
propylene glycol, and PPGs. Other popular humectants in cosmetics include
glycerin, sorbitol (sugar alcohol), hexylene and butylene glycol, urea, and
collagen. Glycerin is one of the most popular humectants used because it
produces the desired result fairly frequently and is low in cost. A category of
humectants called nanolipidgels allow skin to retain moisture, but also
possess antifungal properties. Scientists are also working to discover different
types of humectants; a study published in 2011 concluded that extracts from
wine cakes have the potential to be used as a humectant in cosmetics.
Humectants have been added to skin moisturizing products to treat xerosis.
Some moisturizers tend to weaken the skin barrier function, but studies on
xerosis have proven that moisturizers containing humectants increase desired
moisturizing effects on the affected area without damage to the skin barrier
function. In this xerosis treatments study, some "smarting and stinging" was
also reported from the use of humectant-rich treatment products.
When the humectant glycerol was added to soaps for the cleansing of
wounds, similar effects were found. There was an increase in moisture in the
areas that the soap was applied, however, "further consideration of
conditioning the use of glycerol to improve the absorption of exudates from
wounds for an advanced wound healing is needed." The healing properties of
humectants are therefore uncertain.
Humectants are also added to toothpaste (dentifrice) to stop the product
drying out and cracking in the tube. Sorbitol is commonly used as this also
contributes a sweet flavour to the toothpaste without contributing to tooth
decay.
Tobacco products
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Humectants are used in the manufacturing of some tobacco products, such as
cigarettes, e-cigarettes, and self-rolled tobacco. They are used to control and
maintain the moisture content of the cut tobacco filler and add flavor.
Humectants are vital to the creation of cigarettes.[24] In an examination of
waterpipe smoking, researchers worked to identify substances such as
formaldehyde, acetaldehyde, and acrolein in the smoke of a waterpipe,
discovering that the value of formaldehyde detected in one smoking session
was five times higher than that of a regular cigarette. This data demonstrated
that increasing amounts of humectants in the unburned tobacco lowered the
temperature in the waterpipe head during smoking, so that considerable
amounts of toxic substances were present. Further, e-cigarettes produce
aerosol by heating a humectant containing nicotine without burning tobacco.
Those "vaping" then inhale the aerosol and receive nicotine.[25]
The main health concern regarding e-cigarettes is that their production is not
regulated, and there is immense uncertainty of quality control during
manufacturing. Self-rolled tobacco contains more humectants, which are
added to tobacco to make it taste better and keep from drying out. As the
humectants burn, they unleash chemicals such as acrolein. Humectants are
found in most cigarettes and are considered one of the most dangerous
chemicals found in tobacco.[26]
However, there have been conflicting claims about the degree to which these
products warrant a health concern. In a literary study of e-cigarette health
risks, 388 different symptoms were reported; mouth and throat concerns
generated more negative symptoms than any other group.[27] There are not
enough studies or sufficient evidence to suggest that products, particularly
the contaminants of the aerosol in e-cigarettes, produce health risks at a
concerning level. More research is currently being conducted to find the true
dangers of the use of humectants in cigarettes.[28]
Glycolic acid
A glycolate or glycollate is a salt or ester of glycolic acid.
History
The name "glycolic acid" was coined in 1848 by French chemist Auguste
Laurent (1807–1853). He proposed that the amino acid glycine—which was
then called glycocolle—might be the amine of a hypothetical acid, which he
called "glycolic acid" (acide glycolique).[5]
Glycolic acid was first prepared in 1851 by German chemist Adolph Strecker
(1822–1871) and Russian chemist Nikolai Nikolaevich Sokolov (1826–1877).
They produced it by treating hippuric acid with nitric acid and nitrogen dioxide
to form an ester of benzoic acid and glycolic acid (C6H5C(=O)OCH2COOH),
which they called "benzoglycolic acid" (Benzoglykolsäure; also benzoyl glycolic
acid). They boiled the ester for days with dilute sulfuric acid, thereby
obtaining benzoic acid and glycolic acid (Glykolsäure).[6][7]
Preparation
Glycolic acid can be synthesized in various ways. The predominant
approaches use a catalyzed reaction of formaldehyde with synthesis gas
(carbonylation of formaldehyde), for its low cost.[8]
It is also prepared by the reaction of chloroacetic acid with sodium hydroxide

followed by re-acidification.
Other methods, not noticeably in use, include hydrogenation of oxalic acid,
and hydrolysis of the cyanohydrin derived from formaldehyde.[9] Some of
today's glycolic acids are formic acid-free. Glycolic acid can be isolated from
natural sources, such as sugarcane, sugar beets, pineapple, cantaloupe and
unripe grapes.[10]
Glycolic acid can also be prepared using an enzymatic biochemical process

that may require less energy.[11]
Properties
Glycolic acid is slightly stronger than acetic acid due to the electron-
withdrawing power of the terminal hydroxyl group. The carboxylate group can
coordinate to metal ions forming coordination complexes. Of particular note
are the complexes with Pb2+ and Cu2+ which are significantly stronger than
complexes with other carboxylic acids. This indicates that the hydroxyl group
is involved in complex formation, possibly with the loss of its proton.[12]
Applications
Glycolic acid is used in the textile industry as a dyeing and tanning agent,[13]
in food processing as a flavoring agent and as a preservative, and in the
pharmaceutical industry as a skin care agent. It is also used in adhesives and
plastics.[14] Glycolic acid is often included in emulsion polymers, solvents and
additives for ink and paint in order to improve flow properties and impart
gloss. It is used in surface treatment products that increase the coefficient of
friction on tile flooring. It is the active ingredient in the household cleaning
liquid Pine-Sol.
Skin care
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Rod of Asclepius2.svg
Due to its capability to penetrate skin, glycolic acid finds applications in skin
care products, most often as a chemical peel. Physician-strength peels can
have a pH as low as 0.6 (strong enough to completely keratolyze the
epidermis), while acidities for home peels can be as low as 2.5. Once applied,
glycolic acid reacts with the upper layer of the epidermis, weakening the
binding properties of the lipids that hold the dead skin cells together. This
allows the stratum corneum to be exfoliated, exposing live skin cells.
Organic synthesis
Glycolic acid is a useful intermediate for organic synthesis, in a range of
reactions including: oxidation-reduction, esterification and long chain
polymerization. It is used as a monomer in the preparation of polyglycolic acid
and other biocompatible copolymers (e.g. PLGA). Commercially, important
derivatives include the methyl (CAS# 96-35-5) and ethyl (CAS# 623-50-7)
esters which are readily distillable (boiling points 147–149 °C and 158–159
°C, respectively), unlike the parent acid. The butyl ester (b.p. 178–186 °C) is
a component of some varnishes, being desirable because it is nonvolatile and
has good dissolving properties.[9]
Agriculture
Many plants make glycolic acid during photorespiration. Its role consumes
significant amounts of energy. In 2017 researchers announced a process that
employs a novel protein to reduce energy consumption/loss and prevent
plants from releasing harmful ammonia. The process converts glycolate into
glycerate without using the conventional BASS6 and PLGG1 route.
Αμυγδαλικό οξύ
Από τη Βικιπαίδεια, την ελεύθερη εγκυκλοπαίδεια
Μετάβαση στην πλοήγησηΠήδηση στην αναζήτηση
Αμυγδαλικό οξύ
Kwas migdałowy.svg
(R)-Mandelic acid molecule ball.png
Γενικά
Όνομα IUPAC Αμυγδαλικό οξύ
Άλλες ονομασίες Φαινυλολικό οξύ
υδροξυφαινυλοξικό οξύ
Χημικά αναγνωριστικά
Χημικός τύπος C8H8O3
Μοριακή μάζα 152,149 amu
Αριθμός CAS 90-64-2
SMILES O=C(O)C(O)c1ccccc1
Αριθμός RTECS OO6300000
PubChem CID 1292
ChemSpider ID 1253
Φυσικές ιδιότητες
Σημείο τήξης 119 °C (392 K)
(ρακεμικό μίγμα)
132 έως 135 °C
(καθαρά εναντιομερή)
Σημείο βρασμού 321,8 °C (595,0 K)
Πυκνότητα 1,30 gr/cm3
Διαλυτότητα
στο νερό 15,87 gr/100 ml
Διαλυτότητα
σε άλλους διαλύτες διαλυτό στην αιθανόλη, στον διαιθυλαιθέρα και την
ισοπροπανόλη
Δείκτης διάθλασης ,
nD 1,5204
Εμφάνιση λευκή κρυσταλλική σκόνη
Χημικές ιδιότητες
pKa 3,41
Ελάχιστη θερμοκρασία
ανάφλεξης 162,6 °C (435,8 K)
Εκτός αν σημειώνεται διαφορετικά, τα δεδομένα αφορούν υλικά υπό
κανονικές συνθήκες περιβάλλοντος (25°C, 100 kPa).
Το αμυγδαλικό οξύ ή φαινυλολικό οξύ είναι οργανική χημική ένωση,
ειδικότερα ένα αρωματικό α-υδροξυοξύ, με μοριακό χημικό τύπο
C6H5CH(OH)COOH. Είναι λευκό κρυσταλλικό στερεό, εύκολα διαλυτό στο
νερό και σε πολικούς οργανικούς διαλύτες. Αποτελεί χρήσιμη πρόδρομη
χημική ένωση για τη σύνθεση διάφορων φαρμάκων. Το μόριό του είναι
χειρομορφικό, δηλαδή έχει διεξιόστροφο και αριστερόστροφο ισομερές
(εναντιομερή), και το ρακεμικό μίγμα του είναι γνωστό ως παραμυγδαλικό
οξύ.
Πίνακας περιεχομένων
1 Ιστορία, σύνθεση και παρουσία στη φύση
2 Χρήσεις
3 Παραπομπές
4 Πηγές
Ιστορία, σύνθεση και παρουσία στη φύση
Το αμυγδαλικό οξύ ανακαλύφθηκε το 1831 από τον Γερμανό φαρμακολόγο
Φέρντιναντ Λούντβιχ Βίνκλερ (Ferdinand Ludwig Winckler, 1801-1868) κατά
τη θέρμανση αμυγδαλίνης, δηλαδή αποστάγματος πικραμυγδάλου, με αραιό
υδροχλωρικό οξύ.[1] Το όνομα του αμυγδαλικού οξέος προέρχεται από το
αμύγδαλο. Παράγωγα του αμυγδαλικού οξέος σχηματίζονται ως αποτέλεσμα
μεταβολισμού της αδρεναλίνης και της νοραδρεναλίνης από μονοαμινοξειδάση
και την κατεχολ-O-μεθυλοτρανσφεράση.
Το αμυγδαλικό οξύ παρασκευάζεται συνήθως από την καταλυόμενη με οξέα

υδρόλυση του νιτριλίου του (αμυγδαλονιτρίλιο)[2], το οποίο είναι η
κυανυδρίνη της βενζαλδεΰδης. Το αμυγδαλονιτρίλιο μπορεί να παρασκευασθεί
με την επίδραση βενζαλδεΰδης σε διθειώδες νάτριο, κάτι που δίνει την
αντίστοιχη αντίδραση προσθήκης, και μετά, με επίδραση κυανιούχου νατρίου,
γίνεται υδρόλυση:[3]
Preparation of mandelic acid.png

Μπορεί επίσης να παρασκευασθεί με υδρόλυση φαινυλχλωροξικού οξέος και
διβρομακετοφαινόνης.[4]
Η βιοτεχνολογική παραγωγή 4-υδροξυαμυγδαλικού οξέος και αμυγδαλικού
οξέος από γλυκόζη επιδείχθηκε με γενετικώς τροποποιημένη μαγιά
Saccharomyces cerevisiae, στην οποία ενσωματώθηκε υδροξυαμυγδαλική
συνθετάση που υπάρχει εκ φύσεως στο βακτήριο Amycolatopsis, μερικώς
τροποποιημένη με την ανταλλαγή μιας ακολουθίας γονιδίου.[5]
Αμυγδαλικό οξύ δημιουργείται και από τη βιοαποσύνθεση στυρενίου, όπως

ανιχνεύεται στα ούρα.[6]
Χρήσεις
Το αμυγδαλικό οξύ έχει μακρά ιστορία χρήσεως στην ιατρική ως
αντιβακτηριακό, ιδιαιτέρως στην καταπολέμηση μολύνσεων των ουροφόρων
οδών.[7] Επίσης έχει χρησιμοποιηθεί ως αντιβιοτικό με λήψη από το στόμα και
ως συστατικό καλλυντικών απολεπίσεως προσώπου, αντίστοιχα με άλλα α-
υδροξυοξέα.[8]
Επιπλέον, τα φάρμακα κυκλανδελάτη (cyclandelate) και οματροπίνη είναι

εστέρες του αμυγδαλικού οξέος.
Malic acid
Not to be confused with maleic acid or malonic acid.
"Malate" redirects here. For the district in Manila, see Malate, Manila.
Malic acid
Skeletal structure
Ball-and-stick model
Sample of racemic malic acid.jpg
DL-Malic acid
Names
Preferred IUPAC name
2-Hydroxybutanedioic acid
Other names
Hydroxybutanedioic acid
2-Hydroxysuccinic acid
L-Malic acid
D-Malic acid
(–)-Malic acid
(+)-Malic acid
(S)-Hydroxybutanedioic acid
(R)-Hydroxybutanedioic acid
Identifiers
CAS Number
617-48-1 ☒
6915-15-7 ☒
3D model (JSmol)
Interactive image
ChEBI
CHEBI:6650 check
ChEMBL
ChEMBL1455497 ☒
ChemSpider
510 check
83793 D-(+)-malic acid check
193317 L-(–)-malic acid check
ECHA InfoCard 100.027.293 Edit this at Wikidata
EC Number
230-022-8
E number E296 (preservatives)
IUPHAR/BPS
2480
KEGG
C00149 ☒
PubChem CID
525
UNII
817L1N4CKP check
CompTox Dashboard (EPA)
DTXSID0027640 Edit this at Wikidata
InChI[show]
SMILES[show]
Properties
Chemical formula C4H6O5
Molar mass 134.087 g·mol−1
Density 1.609 g⋅cm−3
Melting point 130 °C (266 °F; 403 K)
Solubility in water 558 g/L (at 20 °C)[1]
Acidity (pKa) pKa1 = 3.40
pKa2 = 5.20[2]
Related compounds
Other anions Malate
Related carboxylic acids Succinic acid
Tartaric acid
Fumaric acid
Related compounds Butanol
Butyraldehyde
Crotonaldehyde
Sodium malate
Except where otherwise noted, data are given for materials in their standard
state (at 25 °C [77 °F], 100 kPa).
☒ verify (what is check☒ ?)
Infobox references
Malic acid is an organic compound with the molecular formula C4H6O5. It is a
dicarboxylic acid that is made by all living organisms, contributes to the sour
taste of fruits, and is used as a food additive. Malic acid has two
stereoisomeric forms (L- and D-enantiomers), though only the L-isomer exists
naturally. The salts and esters of malic acid are known as malates. The
malate anion is an intermediate in the citric acid cycle.
Contents
1 Etymology
2 Biochemistry
3 In food
4 Production and main reactions
5 Interactive pathway map
6 See also
7 References
8 External links
Etymology
The word 'malic' is derived from Latin 'mālum', meaning 'apple'. It is also the
name of the genus Malus, which includes all apples and crabapples; and the
origin of other taxonomic classifications such as Maloideae, Malinae, and
Maleae. This derivation is also seen in the traditional German name for malic
acid, 'Äpfelsäure' meaning 'apple acid' as well as in modern Greek, 'mēlicon
oxy' (Μηλικόν οξύ), after the original European discovery of apples in
modern-day Kazakhstan 2350 years ago by Alexander the Great's
expeditionary foray into Asia.[citation needed]
Biochemistry
L-Malic acid is the naturally occurring form, whereas a mixture of L- and D-
malic acid is produced synthetically.
L-Malic acid
D-Malic acid
Malate plays an important role in biochemistry. In the C4 carbon fixation
process, malate is a source of CO2 in the Calvin cycle. In the citric acid cycle,
(S)-malate is an intermediate, formed by the addition of an -OH group on the
si face of fumarate. It can also be formed from pyruvate via anaplerotic
reactions.
Malate is also synthesized by the carboxylation of phosphoenolpyruvate in the

guard cells of plant leaves. Malate, as a double anion, often accompanies
potassium cations during the uptake of solutes into the guard cells in order to
maintain electrical balance in the cell. The accumulation of these solutes
within the guard cell decreases the solute potential, allowing water to enter
the cell and promote aperture of the stomata.
In food
Malic acid was first isolated from apple juice by Carl Wilhelm Scheele in 1785.
[3] Antoine Lavoisier in 1787 proposed the name acide malique, which is
derived from the Latin word for apple, mālum—as is its genus name Malus.[4]
[5] In German it is named Äpfelsäure (or Apfelsäure) after plural or singular
of the fruit apple, but the salt(s) Malat(e). Malic acid is the main acid in many
fruits, including apricots, blackberries, blueberries, cherries, grapes,
mirabelles, peaches, pears, plums, and quince[6] and is present in lower
concentrations in other fruits, such as citrus.[7] It contributes to the sourness
of unripe apples. Sour apples contain high proportions of the acid. It is
present in grapes and in most wines with concentrations sometimes as high
as 5 g/l.[8] It confers a tart taste to wine; the amount decreases with
increasing fruit ripeness. The taste of malic acid is very clear and pure in
rhubarb, a plant for which it is the primary flavor. It is also a component of
some artificial vinegar flavors, such as "salt and vinegar" flavored potato
chips.[9]
In citrus, fruits produced in organic farming contain higher levels of malic acid
than fruits produced in conventional agriculture.[7]
The process of malolactic fermentation converts malic acid to much milder

lactic acid. Malic acid occurs naturally in all fruits and many vegetables, and is
generated in fruit metabolism.[10]
Malic acid, when added to food products, is denoted by E number E296. It is
sometimes used with or in place of the less sour citric acid in sour sweets.
These sweets are sometimes labeled with a warning stating that excessive
consumption can cause irritation of the mouth. It is approved for use as a
food additive in the EU,[11] US[12] and Australia and New Zealand[13]
(where it is listed by its INS number 296).
Malic acid provides 10 kJ (2.39 kilocalories) of energy per gram during

digestion.[14]
Production and main reactions

Racemic malic acid is produced industrially by the double hydration of maleic
anhydride. In 2000, American production capacity was 5000 tons per year.
Both enantiomers may be separated by chiral resolution of the racemic
mixture, and the (S)- enantiomer may be specifically obtained by
fermentation of fumaric acid.[15]
Self-condensation of malic acid with fuming sulfuric acid gives the pyrone
coumalic acid:[16]
Coumalic Acid Synthesis

Malic acid was important in the discovery of the Walden inversion and the
Walden cycle, in which (−)-malic acid first is converted into (+)-chlorosuccinic
acid by action of phosphorus pentachloride. Wet silver oxide then converts
the chlorine compound to (+)-malic acid, which then reacts with PCl5 to the
(−)-chlorosuccinic acid. The cycle is completed when silver oxide takes this
compound back to (−)-malic acid.
Citric acid
"E330" redirects here. For the locomotive, see FS Class E330.
For vitamin C, see ascorbic acid.
Citric acid
Zitronensäure - Citric acid.svg
Citric-acid-3D-balls.png
Zitronensäure Kristallzucht.jpg
Names
IUPAC name
Citric acid[1]
Systematic IUPAC name
2-Hydroxypropane-1,2,3-tricarboxylic acid
Identifiers
CAS Number
77-92-9 check
3D model (JSmol)
Interactive image
ChEBI
CHEBI:30769 check
ChEMBL
ChEMBL1261 check
ChemSpider
305 check
DrugBank
DB04272 check
EC Number
201-069-1
E number E330 (antioxidants, ...)
IUPHAR/BPS
2478
KEGG
D00037 check
PubChem CID
311
22230 (monohydrate)
RTECS number
GE7350000
UNII
XF417D3PSL check
InChI[show]
SMILES[show]
Properties
Chemical formula C6H8O7
Molar mass 192.123 g/mol (anhydrous), 210.14 g/mol (monohydrate)[2]
Appearance Crystalline white solid
Odor Odorless
Density 1.665 g/cm3 (anhydrous)
1.542 g/cm3 (18 °C, monohydrate)
Melting point 156 °C (313 °F; 429 K)
Boiling point 310 °C (590 °F; 583 K) decomposes from 175 °C[3]
Solubility in water 54% w/w (10 °C)
59.2% w/w (20 °C)
64.3% w/w (30 °C)
68.6% w/w (40 °C)
70.9% w/w (50 °C)
73.5% w/w (60 °C)
76.2% w/w (70 °C)
78.8% w/w (80 °C)
81.4% w/w (90 °C)
84% w/w (100 °C)[4]
Solubility Soluble in acetone, alcohol, ether, ethyl acetate, DMSO
Insoluble in C
6H
6, CHCl3, CS2, toluene[3]
Solubility in ethanol 62 g/100 g (25 °C)[3]
Solubility in amyl acetate 4.41 g/100 g (25 °C)[3]
Solubility in diethyl ether 1.05 g/100 g (25 °C)[3]
Solubility in 1,4-Dioxane 35.9 g/100 g (25 °C)[3]
log P −1.64
Acidity (pKa) pKa1 = 3.13[5]
pKa2 = 4.76[5]
pKa3 = 6.39,[6] 6.40[7]
Refractive index (nD) 1.493–1.509 (20 °C)[4]
1.46 (150 °C)[3]
Viscosity 6.5 cP (50% aq. sol.)[4]
Structure
Crystal structure Monoclinic
Thermochemistry
Heat capacity (C) 226.51 J/(mol·K) (26.85 °C)[8]
Std molar
entropy (So298) 252.1 J/(mol·K)[8]
Std enthalpy of
formation (ΔfH⦵298) −1543.8 kJ/mol[4]
Heat of combustion, higher value (HHV) 1985.3 kJ/mol (474.5 kcal/mol, 2.47
kcal/g),[4] 1960.6 kJ/mol[8]
1972.34 kJ/mol (471.4 kcal/mol, 2.24 kcal/g) (monohydrate)[4]
Pharmacology
ATC code A09AB04 (WHO)
Hazards
Main hazards Skin and eye irritant
Safety data sheet HMDB
GHS pictograms GHS07: Harmful[5]
GHS Signal word Warning
GHS hazard statements H319[5]
GHS precautionary statements P305+351+338[5]
NFPA 704 (fire diamond)
NFPA 704 four-colored diamond
010
Flash point 155 °C (311 °F; 428 K)
Autoignition
temperature 345 °C (653 °F; 618 K)
Explosive limits 8%[5]
Lethal dose or concentration (LD, LC):
LD50 (median dose)3000 mg/kg (rats, oral)
state (at 25 °C [77 °F], 100 kPa).
check verify (what is check☒ ?)
Infobox references
Citric acid is a weak organic acid that has the molecular formula C6H8O7. It
occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the
citric acid cycle, which occurs in the metabolism of all aerobic organisms.
More than two million tons of citric acid are manufactured every year. It is
used widely as an acidifier, as a flavoring and a chelating agent.[9]
A citrate is a derivative of citric acid; that is, the salts, esters, and the
polyatomic anion found in solution. An example of the former, a salt is
trisodium citrate; an ester is triethyl citrate. When part of a salt, the formula
of the citrate anion is written as C
6H
5O3−
7 or C
3H
5O(COO)3−
3.
Contents
1 Natural occurrence and industrial production
2 Chemical characteristics
3 Biochemistry
3.1 Citric acid cycle
3.2 Other biological roles
4 Applications
4.1 Food and drink
4.2 Cleaning and chelating agent
4.3 Cosmetics, pharmaceuticals, dietary supplements, and foods
4.4 Other uses
5 Synthesis of solid materials from small molecules
6 Safety
7 Compendial status
8 See also
9 References
Natural occurrence and industrial production
Lemons, oranges, limes, and other citrus fruits possess high concentrations of
citric acid
Citric acid exists in a variety of fruits and vegetables, most notably citrus
fruits. Lemons and limes have particularly high concentrations of the acid; it
can constitute as much as 8% of the dry weight of these fruits (about 47 g/l
in the juices[10]).[a] The concentrations of citric acid in citrus fruits range
from 0.005 mol/L for oranges and grapefruits to 0.30 mol/L in lemons and
limes; these values vary within species depending upon the cultivar and the
circumstances in which the fruit was grown.
Industrial-scale citric acid production first began in 1890 based on the Italian
citrus fruit industry, where the juice was treated with hydrated lime (calcium
hydroxide) to precipitate calcium citrate, which was isolated and converted
back to the acid using diluted sulfuric acid.[11] In 1893, C. Wehmer
discovered Penicillium mold could produce citric acid from sugar. However,
microbial production of citric acid did not become industrially important until
World War I disrupted Italian citrus exports.
In 1917, American food chemist James Currie discovered certain strains of the
mold Aspergillus niger could be efficient citric acid producers, and the
pharmaceutical company Pfizer began industrial-level production using this
technique two years later, followed by Citrique Belge in 1929. In this
production technique, which is still the major industrial route to citric acid
used today, cultures of A. niger are fed on a sucrose or glucose-containing
medium to produce citric acid. The source of sugar is corn steep liquor,
molasses, hydrolyzed corn starch, or other inexpensive, sugary solution.[12]
After the mold is filtered out of the resulting solution, citric acid is isolated by
precipitating it with calcium hydroxide to yield calcium citrate salt, from which
citric acid is regenerated by treatment with sulfuric acid, as in the direct
extraction from citrus fruit juice.
In 1977, a patent was granted to Lever Brothers for the chemical synthesis of
citric acid starting either from aconitic or isocitrate/alloisocitrate calcium salts
under high pressure conditions; this produced citric acid in near quantitative
conversion under what appeared to be a reverse, non-enzymatic Krebs cycle
reaction.[13]
Global production was in excess of 2,000,000 tons in 2018.[14] More than

50% of this volume was produced in China. More than 50% was used as an
acidity regulator in beverages, some 20% in other food applications, 20% for
detergent applications, and 10% for applications other than food, such as
cosmetics, pharmaceuticals, and in the chemical industry.[citation needed]
Chemical characteristics
Citric acid crystals (crystallized from an aqueous solution) under a
microscope.
Speciation diagram for a 10-millimolar solution of citric acid

Citric acid was first isolated in 1784 by the chemist Carl Wilhelm Scheele, who
crystallized it from lemon juice.[15][11][16] It can exist either in an
anhydrous (water-free) form or as a monohydrate. The anhydrous form
crystallizes from hot water, while the monohydrate forms when citric acid is
crystallized from cold water. The monohydrate can be converted to the
anhydrous form at about 78 °C. Citric acid also dissolves in absolute
(anhydrous) ethanol (76 parts of citric acid per 100 parts of ethanol) at 15 °C.
It decomposes with loss of carbon dioxide above about 175 °C.
Citric acid is normally considered to be a tribasic acid, with pKa values,

extrapolated to zero ionic strength, of 2.92, 4.28, and 5.21 at 25 °C.[17] The
pKa of the hydroxyl group has been found, by means of 13C NMR
spectroscopy, to be 14.4.[18] The speciation diagram shows that solutions of
citric acid are buffer solutions between about pH 2 and pH 8. In biological
systems around pH 7, the two species present are the citrate ion and mono-
hydrogen citrate ion. The SSC 20X hybridization buffer is an example in
common use.[19] Tables compiled for biochemical studies[20] are available.
On the other hand, the pH of a 1 mM solution of citric acid will be about 3.2.
The pH of fruit juices from citrus fruits like oranges and lemons depends on
the citric acid concentration, being lower for higher acid concentration and
conversely.
Acid salts of citric acid can be prepared by careful adjustment of the pH

before crystallizing the compound. See, for example, sodium citrate.
The citrate ion forms complexes with metallic cations. The stability constants
for the formation of these complexes are quite large because of the chelate
effect. Consequently, it forms complexes even with alkali metal cations.
However, when a chelate complex is formed using all three carboxylate
groups, the chelate rings have 7 and 8 members, which are generally less
stable thermodynamically than smaller chelate rings. In consequence, the
hydroxyl group can be deprotonated, forming part of a more stable 5-
membered ring, as in ammonium ferric citrate, (NH
4)
5Fe(C
6H
4O
7)
2·2H
2O.[21]
Citric acid can be esterified at one or more of the carboxylic acid functional
groups on the molecule (using a variety of alcohols), to form any of a variety
of mono-, di-, tri-, and mixed esters.[citation needed]
Biochemistry
Citric acid cycle
Main article: Citric acid cycle
Citrate is an intermediate in the TCA cycle (aka TriCarboxylic Acid cycle, or
Krebs cycle, Szent-Györgyi), a central metabolic pathway for animals, plants,
and bacteria. Citrate synthase catalyzes the condensation of oxaloacetate with
acetyl CoA to form citrate. Citrate then acts as the substrate for aconitase and
is converted into aconitic acid. The cycle ends with regeneration of
oxaloacetate. This series of chemical reactions is the source of two-thirds of
the food-derived energy in higher organisms. Hans Adolf Krebs received the
1953 Nobel Prize in Physiology or Medicine for the discovery.
Some bacteria (notably E. coli) can produce and consume citrate internally as
part of their TCA cycle, but are unable to use it as food because they lack the
enzymes required to import it into the cell. After tens of thousand of
evolutions in a minimal glucose medium that also contained citrate during
Richard Lenski's Long-Term Evolution Experiment, a variant E. coli evolved
with the ability to grow aerobically on citrate. Zachary Blount, a student of
Lenski's, and colleagues studied these "Cit+" E. coli[22][23] as a model for
how novel traits evolve. They found evidence that, in this case, the innovation
was caused by a rare duplication mutation due to the accumulation of several
prior "potentiating" mutations, the identity and effects of which are still under
study. The evolution of the Cit+ trait has been considered a notable example
of the role of historical contingency in evolution.
Other biological roles
Citrate can be transported out of the mitochondria and into the cytoplasm,
then broken down into acetyl-CoA for fatty acid synthesis, and into
oxaloacetate. Citrate is a positive modulator of this conversion, and
allosterically regulates the enzyme acetyl-CoA carboxylase, which is the
regulating enzyme in the conversion of acetyl-CoA into malonyl-CoA (the
commitment step in fatty acid synthesis). In short, citrate is transported into
the cytoplasm, converted into acetyl CoA, which is then converted into
malonyl CoA by acetyl CoA carboxylase, which is allosterically modulated by
citrate.
High concentrations of cytosolic citrate can inhibit phosphofructokinase, the

catalyst of a rate-limiting step of glycolysis. This effect is advantageous: high
concentrations of citrate indicate that there is a large supply of biosynthetic
precursor molecules, so there is no need for phosphofructokinase to continue
to send molecules of its substrate, fructose 6-phosphate, into glycolysis.
Citrate acts by augmenting the inhibitory effect of high concentrations of ATP,
another sign that there is no need to carry out glycolysis.[24]
Citrate is a vital component of bone, helping to regulate the size of apatite

crystals.[25]
Applications
Food and drink
Powdered citric acid being used to prepare lemon pepper seasoning

Because it is one of the stronger edible acids, the dominant use of citric acid
is as a flavoring and preservative in food and beverages, especially soft drinks
and candies.[11] Within the European Union it is denoted by E number E330.
Citrate salts of various metals are used to deliver those minerals in a
biologically available form in many dietary supplements. Citric acid has 247
kcal per 100 g.[26] In the United States the purity requirements for citric acid
as a food additive are defined by the Food Chemicals Codex, which is
published by the United States Pharmacopoeia (USP).
Citric acid can be added to ice cream as an emulsifying agent to keep fats
from separating, to caramel to prevent sucrose crystallization, or in recipes in
place of fresh lemon juice. Citric acid is used with sodium bicarbonate in a
wide range of effervescent formulae, both for ingestion (e.g., powders and
tablets) and for personal care (e.g., bath salts, bath bombs, and cleaning of
grease). Citric acid sold in a dry powdered form is commonly sold in markets
and groceries as "sour salt", due to its physical resemblance to table salt. It
has use in culinary applications, as an alternative to vinegar or lemon juice,
where a pure acid is needed. Citric acid can be used in food coloring to
balance the pH level of a normally basic dye.[citation needed]
Cleaning and chelating agent

Citric acid is an excellent chelating agent, binding metals by making them
soluble. It is used to remove and discourage the buildup of limescale from
boilers and evaporators.[11] It can be used to treat water, which makes it
useful in improving the effectiveness of soaps and laundry detergents. By
chelating the metals in hard water, it lets these cleaners produce foam and
work better without need for water softening. Citric acid is the active
ingredient in some bathroom and kitchen cleaning solutions. A solution with a
six percent concentration of citric acid will remove hard water stains from
glass without scrubbing. Citric acid can be used in shampoo to wash out wax
and coloring from the hair. Illustrative of its chelating abilities, citric acid was
the first successful eluant used for total ion-exchange separation of the
lanthanides, during the Manhattan Project in the 1940s. In the 1950s, it was
replaced by the far more efficient EDTA.
In industry, it is used to dissolve rust from steel and passivate stainless steels.
[27]
Cosmetics, pharmaceuticals, dietary supplements, and foods

Citric acid is used as an acidulant in creams, gels, and liquids. Used in foods
and dietary supplements, it may be classified as a processing aid if it was
added for a technical or functional effect (e.g. acidulent, chelator, viscosifier,
etc.). If it is still present in insignificant amounts, and the technical or
functional effect is no longer present, it may be exempt from labeling <21
CFR §101.100(c)>.
Citric acid is an alpha hydroxy acid and is an active ingredient in chemical skin
peels.[citation needed]
Citric acid is commonly used as a buffer to increase the solubility of brown
heroin.[28]
Citric acid is used as one of the active ingredients in the production of facial
tissues with antiviral properties.[29]
Other uses
The buffering properties of citrates are used to control pH in household
cleaners and pharmaceuticals.
Citric acid is used as an odorless alternative to white vinegar for home dyeing
with acid dyes.
Sodium citrate is a component of Benedict's reagent, used for identification

both qualitatively and quantitatively of reducing sugars.
Citric acid can be used as an alternative to nitric acid in passivation of

stainless steel.[30]
Citric acid can be used as a lower-odor stop bath as part of the process for
developing photographic film. Photographic developers are alkaline, so a mild
acid is used to neutralize and stop their action quickly, but commonly used
acetic acid leaves a strong vinegar odor in the darkroom.[31]
Citric acid/potassium-sodium citrate can be used as a blood acid regulator.
Soldering flux. Citric acid is an excellent soldering flux,[32] either dry or as a

concentrated solution in water. It should be removed after soldering,
especially with fine wires, as it is mildly corrosive. It dissolves and rinses
quickly in hot water.
Synthesis of solid materials from small molecules

In materials science, the Citrate-gel method is a process similar to the sol-gel
method, which is a method for producing solid materials from small
molecules. During the synthetic process, metal salts or alkoxides are
introduced into a citric acid solution. The formation of citric complexes is
believed to balance the difference in individual behavior of ions in solution,
which results in a better distribution of ions and prevents the separation of
components at later process stages. The polycondensation of ethylene glycol
and citric acid starts above 100 °С, resulting in polymer citrate gel formation.
Safety
Although a weak acid, exposure to pure citric acid can cause adverse effects.
Inhalation may cause cough, shortness of breath, or sore throat. Over-
ingestion may cause abdominal pain and sore throat. Exposure of
concentrated solutions to skin and eyes can cause redness and pain.[33]
Long-term or repeated consumption may cause erosion of tooth enamel.
Tartaric acid
Tartaric acid[1]
Tartaric acid.svg
Tartaric-acid-3D-balls.png
Names
Preferred IUPAC name
2,3-Dihydroxybutanedioic acid
Other names
Tartaric acid
2,3-Dihydroxysuccinic acid
Threaric acid
Racemic acid
Uvic acid
Paratartaric acid
Winestone
Identifiers
CAS Number
526-83-0 check
3D model (JSmol)
Interactive image
ChEBI
CHEBI:15674 check
ChEMBL
ChEMBL333714 check
ChEMBL1200861 check
ChemSpider
852 check
DrugBank
DB01694 check
KEGG
C00898 check
MeSH tartaric+acid
PubChem CID
875
InChI[show]
SMILES[show]
Properties
Chemical formula C4H6O6 (Basic formula)
HO2CCH(OH)CH(OH)CO2H (Structural formula)
Molar mass 150.087 g/mol
Appearance White powder
Density 1.79 g/mL (H2O)
Melting point 171 to 174 °C (340 to 345 °F; 444 to 447 K) (L or D-tartaric;
pure)
206 °C (DL, racemic)
165–166 °C (meso-anhydrous)
146–148 °C (meso-hydrous)[3]
Solubility in water
1.33 kg/L (L or D-tartaric)
0.21 kg/L (DL, racemic)
1.25 kg/L ("meso")
Acidity (pKa) L(+) 25 °C :
pKa1= 2.89, pKa2= 4.40
meso 25 °C:
pKa1= 3.22, pKa2= 4.85
[2]
Conjugate base Bitartrate

Magnetic susceptibility (χ) −67.5·10−6 cm3/mol
Hazards
EU classification (DSD) (outdated) Irritant(Xi)
R-phrases (outdated) R36
Related compounds
Other cations Monosodium tartrate
Disodium tartrate
Monopotassium tartrate
Dipotassium tartrate
Related carboxylic acids Butyric acid
Succinic acid
Dimercaptosuccinic acid
Malic acid
Maleic acid
Fumaric acid
Related compounds 2,3-Butanediol
Cichoric acid
state (at 25 °C [77 °F], 100 kPa).
check verify (what is check☒ ?)
Infobox references
Tartaric acid is a white, crystalline organic acid that occurs naturally in many
fruits, most notably in grapes, but also in bananas, tamarinds, and citrus.[4]
Its salt, potassium bitartrate, commonly known as cream of tartar, develops
naturally in the process of fermentation. It is commonly mixed with sodium
bicarbonate and is sold as baking powder used as a leavening agent in food
preparation. The acid itself is added to foods as an antioxidant E334 and to
impart its distinctive sour taste.
Tartaric acid is an alpha-hydroxy-carboxylic acid, is diprotic and aldaric in acid

characteristics, and is a dihydroxyl derivative of succinic acid.
Contents
1 History
2 Stereochemistry
3 Production
3.1 L-(+)-Tartaric acid
3.2 Racemic tartaric acid
3.3 meso-Tartaric acid
4 Reactivity
5 Derivatives
6 Tartaric acid in wine
7 Tartaric acid in citrus
8 In superconductors
9 Applications
10 References
11 External links
History
Tartaric acid has been known to winemakers for centuries. Written record of
its extraction from wine-making residues was made circa 800 AD, by the
alchemist Jābir ibn Hayyān.[5] The chemical process for extraction was
developed in 1769 by the Swedish chemist Carl Wilhelm Scheele.[6]
Tartaric acid played an important role in the discovery of chemical chirality.

This property of tartaric acid was first observed in 1832 by Jean Baptiste Biot,
who observed its ability to rotate polarized light.[7][8] Louis Pasteur
continued this research in 1847 by investigating the shapes of sodium
ammonium tartrate crystals, which he found to be chiral. By manually sorting
the differently shaped crystals, Pasteur was the first to produce a pure sample
of levotartaric acid.[9][10][11][12][13]
Stereochemistry
Tartaric acid crystals drawn as if seen through an optical microscope

Naturally occurring tartaric acid is chiral, and is a useful raw material in
organic chemical synthesis. The naturally occurring form of the acid is
dextrotartaric acid or L-(+)-tartaric acid (obsolete name d-tartaric acid).
Because it is available naturally, it is slightly cheaper than its enantiomer and
the meso isomer. The dextro and levo prefixes are archaic terms.[14] Modern
textbooks refer to the natural form as (2R,3R)-tartaric acid (L-(+)-tartaric
acid), and its enantiomer as (2S,3S)-tartaric acid (D-(-)-tartaric acid). The
meso diastereomer is (2R,3S)-tartaric acid (which is identical with ‘(2S,3R)-
tartaric acid’).
Whereas the two chiral stereoisomers rotate plane polarized light in opposite
directions, solutions of meso-tartaric acid do not rotate plane-polarized light.
The absence of optical activity is due to a mirror plane in the molecule
[segmented line in picture below].[15][16]
Tartaric acid in Fehling's solution binds to copper(II) ions, preventing the

formation of insoluble hydroxide salts.
DL-tartaric acid (racemic acid) (when in 1:1 ratio) mesotartaric acid
dextrotartaric acid
(L-(+)-tartaric acid) levotartaric acid
(D-(−)-tartaric acid)
L-tartaric acid.png D-tartaric acid.png Meso-Weinsäure Spiegel.svg
Forms of tartaric acid
Common name Tartaric acid Levotartaric acid Dextrotartaric acid
Mesotartaric acid Racemic acid
Synonyms (2S,3S)-tartaric acid
(S,S)-tartaric acid
(−)-tartaric acid
l-tartaric acid (obsolete)
levotartaric acid
D-tartaric acid
D-threaric acid
('unnatural isomer')[17] (2R,3R)-tartaric acid
(R,R)-tartaric acid
(+)-tartaric acid
d-tartaric acid (obsolete)
L-tartaric acid
L-threaric acid
(‘natural isomer’)[18] (2R,3S)-tartaric acid
meso-tartaric acid
erythraric acid rac-(2R,3S)-tartaric acid
(2RS,3SR)-tartaric acid
(±)-tartaric acid
DL-tartaric acid
dl-tartaric acid (obsolete)
paratartaric acid
uvic acid
PubChem CID 875 from PubChem CID 439655 from PubChem
CID 444305 from PubChem CID 78956 from PubChem CID 5851
from PubChem
EINECS number 205-695-6 201-766-0 205-696-1 205-105-7
CAS number 526-83-0 147-71-7 87-69-4 147-73-9 133-37-9
Production
L-(+)-Tartaric acid
The L-(+)-tartaric acid isomer of tartaric acid is industrially produced in the
largest amounts. It is obtained from lees, a solid byproduct of fermentations.
The former byproducts mostly consist of potassium bitartrate (KHC4H4O6).
This potassium salt is converted to calcium tartrate (CaC4H4O6) upon
treatment with milk of lime (Ca(OH)2):[19]
KO2CCH(OH)CH(OH)CO2H + Ca(OH)2 → Ca(O2CCH(OH)CH(OH)CO2) + KOH

+ H2O
In practice, higher yields of calcium tartrate are obtained with the addition of
calcium chloride. Calcium tartrate is then converted to tartaric acid by treating
the salt with aqueous sulfuric acid:
Ca(O2CCH(OH)CH(OH)CO2) + H2SO4 → HO2CCH(OH)CH(OH)CO2H +

CaSO4
Racemic tartaric acid
Racemic tartaric acid (i.e.: a 50:50 mixture of D-(−)-tartaric acid and L-(+)-
tartaric acid molecules, racemic acid) can be prepared in a multistep reaction
from maleic acid. In the first step, the maleic acid is epoxidized by hydrogen
peroxide using potassium tungstate as a catalyst.[19]
HO2CC2H2CO2H + H2O2 → OC2H2(CO2H) 2

In the next step, the epoxide is hydrolyzed.
OC2H2(CO2H)2 + H2O → (HOCH)2(CO2H)2

meso-Tartaric acid
meso-Tartaric acid is formed via thermal isomerization. dextro-Tartaric acid is
heated in water at 165 °C for about 2 days. meso-Tartaric acid can also be
prepared from dibromosuccinic acid using silver hydroxide:[20]
HO2CCHBrCHBrCO2H + 2 AgOH → HO2CCH(OH)CH(OH)CO2H + 2 AgBr

meso-Tartaric acid can be separated from residual racemic acid by
crystallization, the racemate being less soluble.
Reactivity
L-(+)-tartaric acid, can participate in several reactions. As shown the reaction
scheme below, dihydroxymaleic acid is produced upon treatment of L-(+)-
tartaric acid with hydrogen peroxide in the presence of a ferrous salt.
HO2CCH(OH)CH(OH)CO2H + H2O2 → HO2CC(OH)C(OH)CO2H + 2 H2O

Dihydroxymaleic acid can then be oxidized to tartronic acid with nitric acid.
[21]
Derivatives
Tartar emetic
Commercially produced tartaric acid

Important derivatives of tartaric acid include its salts, cream of tartar
(potassium bitartrate), Rochelle salt (potassium sodium tartrate, a mild
laxative), and tartar emetic (antimony potassium tartrate).[22][23][24]
Diisopropyl tartrate is used as a co-catalyst in asymmetric synthesis.
Tartaric acid is a muscle toxin, which works by inhibiting the production of

malic acid, and in high doses causes paralysis and death.[25] The median
lethal dose (LD50) is about 7.5 grams/kg for a human, 5.3 grams/kg for
rabbits, and 4.4 grams/kg for mice.[26] Given this figure, it would take over
500 g (18 oz) to kill a person weighing 70 kg (150 lb), so it may be safely
included in many foods, especially sour-tasting sweets. As a food additive,
tartaric acid is used as an antioxidant with E number E334; tartrates are other
additives serving as antioxidants or emulsifiers.
When cream of tartar is added to water, a suspension results which serves to
clean copper coins very well, as the tartrate solution can dissolve the layer of
copper(II) oxide present on the surface of the coin. The resulting copper(II)-
tartrate complex is easily soluble in water.
Tartaric acid in wine

See also: Acids in wine and Tartrate
Unpurified potassium bitartrate can take on the color of the grape juice from
which it was separated.
Tartaric acid may be most immediately recognizable to wine drinkers as the
source of "wine diamonds", the small potassium bitartrate crystals that
sometimes form spontaneously on the cork or bottom of the bottle. These
"tartrates" are harmless, despite sometimes being mistaken for broken glass,
and are prevented in many wines through cold stabilization (which is not
always preferred since it can change the wine's profile). The tartrates
remaining on the inside of aging barrels were at one time a major industrial
source of potassium bitartrate.
Tartaric acid plays an important role chemically, lowering the pH of

fermenting "must" to a level where many undesirable spoilage bacteria
cannot live, and acting as a preservative after fermentation. In the mouth,
tartaric acid provides some of the tartness in the wine, although citric and
malic acids also play a role.
Tartaric acid in citrus

Results from a study showed that in citrus, fruits produced in organic farming
contain higher levels of tartaric acid than fruits produced in conventional
agriculture.[27]
In superconductors
Tartaric acid seems to increase the critical temperature in certain
superconductors, by supposedly raising the oxidation grade, while the
mechanism of this phenomenon is still not precisely known.[28]
Applications
Tartaric acid and its derivatives have a plethora of uses in the field of
pharmaceuticals. For example, it has been used in the production of
effervescent salts, in combination with citric acid, to improve the taste of oral
medications.[21] The potassium antimonyl derivative of the acid known as
tartar emetic is included, in small doses, in cough syrup as an expectorant.
Tartaric acid also has several applications for industrial use. The acid has
been observed to chelate metal ions such as calcium and magnesium.
Therefore, the acid has served in the farming and metal industries as a
chelating agent for complexing micronutrients in soil fertilizer and for cleaning
metal surfaces consisting of aluminium, copper, iron, and alloys of these
metals, respectively.[19]
Sebaceous gland
Sebaceous gland
Schematic view of hair follicle and sebaceous

gland
Cross-section of all skin layers. A hair
follicle with associated structures. (Sebaceous
glands labeled at center left.)
Details
Identifiers
Latin glandula sebacea
MeSH D012627
TA98 A16.0.00.030
A15.2.07.044
TA2 7082
FMA 59160
Anatomical terminology
[edit on Wikidata]
A sebaceous gland is a microscopic exocrine gland in the skin that opens

into a hair follicle to secrete an oily or waxy matter, called sebum, which
lubricates the hair and skin of mammals.[1] In humans, sebaceous glands
occur in the greatest number on the face and scalp, but also on all parts of
the skin except the palms of the hands and soles of the feet. In the
eyelids, meibomian glands, also called tarsal glands, are a type of sebaceous
gland that secrete a special type of sebum into tears. Surrounding the female
nipple, areolar glands are specialized sebaceous glands for lubricating the
nipple. Fordyce spots are benign, visible, sebaceous glands found usually on
the lips, gums and inner cheeks, and genitals.
Several related medical conditions involve sebum—
including acne, hyperplasia, and sebaceous adenoma. These are usually
attributable to overactive sebaceous glands, which produce excess sebum.
Contents
 1Structure
o 1.1Location
o 1.2Development
 2Function
o 2.1Sebum
o 2.2Immune function and nutrition
o 2.3Unique sebaceous glands
 3Clinical significance
o 3.1Acne
o 3.2Other
 4History
 5Other animals
 6See also
 7References
 8External links
Structure[edit]
Location[edit]
Sebaceous glands are found throughout all areas of the skin, except
the palms of the hands and soles of the feet.[2] There are two types of
sebaceous gland, those connected to hair follicles and those that exist
independently.[3]
Sebaceous glands are found in hair-covered areas, where they are connected
to hair follicles. One or more glands may surround each hair follicle, and the
glands themselves are surrounded by arrector pili muscles, forming a
pilosebaceous unit. The glands have an acinar structure (like a many-lobed
berry), in which multiple glands branch off a central duct. The glands deposit
sebum on the hairs and bring it to the skin surface along the hair shaft. The
structure, consisting of hair, hair follicle, arrector pili muscles, and sebaceous
gland, is an epidermal invagination known as a pilosebaceous unit.[3]
Sebaceous glands are also found in hairless areas (glabrous skin) of
the eyelids, nose, penis, labia minora, the inner mucosal membrane of
the cheek, and nipples.[3] Some sebaceous glands have unique names.
Sebaceous glands on the lip and mucosa of the cheek, and on the genitalia,
are known as Fordyce spots, and glands on the eyelids are known
as meibomian glands. Sebaceous glands of the breast are also known
as Montgomery's glands.[4]
Development[edit]
Sebaceous glands are first visible from the 13th to the 16th week of fetal
development, as bulgings off hair follicles.[5] Sebaceous glands develop from
the same tissue that gives rise to the epidermis of the skin. Overexpression of
the signalling factors Wnt, Myc and SHH all increase the likelihood of
sebaceous gland presence.[4]
The sebaceous glands of a human fetus secrete a substance called vernix
caseosa, a waxy, translucent white substance coating the skin of newborns.
[6]
After birth, activity of the glands decreases until there is almost no activity
during ages 2–6 years, and then increases to a peak of activity
during puberty, due to heightened levels of androgens.[5]
Base of pilosebaceous unit

Insertion of sebaceous glands into hair shaft

Sagittal section through the upper eyelid.


A hair follicle with associated structures

Scalp cross section showing hair follicle with sebaceous glands.

Function[edit]
Relative to keratinocytes that make up the hair follicle, sebaceous glands are
composed of huge cells with many large vesicles that contain the sebum.
[7]
These cells express Na+ and Cl− ion channels, ENaC and CFTR (see Fig. 6
and Fig. 7 in reference[7]).
Sebaceous glands secrete the oily, waxy substance
called sebum (Latin: fat, tallow) that is made of triglycerides, wax
esters, squalene, and metabolites of fat-producing cells. Sebum lubricates the
skin and hair of mammals.[8] Sebaceous secretions in conjunction
with apocrine glands also play an important thermoregulatory role. In hot
conditions, the secretions emulsify the sweat produced by the eccrine glands
and this produces a sheet of sweat that is not readily lost in drops of sweat.
This is of importance in delaying dehydration. In colder conditions, the nature
of sebum becomes more lipid, and in coating the hair and skin, rain is
effectively repelled.[9][10]
Sebum is produced in a holocrine process, in which cells within the sebaceous
gland rupture and disintegrate as they release the sebum and the cell
remnants are secreted together with the sebum.[11][12] The cells are constantly
replaced by mitosis at the base of the duct.[3]
Sebum[edit]
Sebum, secreted by the sebaceous gland in humans, is primarily composed
of triglycerides (≈41%), wax esters (≈26%), squalene (≈12%), and free fatty
acids (≈16%).[6][13] The composition of sebum varies across species.[13] Wax
esters and squalene are unique to sebum and not produced as final products
anywhere else in the body.[4] Sapienic acid is a sebum fatty acid that is unique
to humans, and is implicated in the development of acne. [14] Sebum is
odorless, but its breakdown by bacteria can produce strong odors. [15]
Sex steroids are known to affect the rate of sebum secretion; androgens such
as testosterone have been shown to stimulate secretion, and estrogens have
been shown to inhibit secretion.[16] Dihydrotestosterone acts as the primary
androgen in the prostate and in hair follicles. [17][18]
Immune function and nutrition[edit]
Sebaceous glands are part of the body's integumentary system and serve to
protect the body against microorganisms. Sebaceous glands secrete acids that
form the acid mantle. This is a thin, slightly acidic film on the surface of
the skin that acts as a barrier to microbes that might penetrate the skin.
[19]
The pH of the skin is between 4.5 and 6.2,[20] an acidity that helps to
neutralize the alkaline nature of contaminants.[21] Sebaceous lipids help
maintain the integrity of the skin barrier [9][22][23] and supply vitamin E to the
skin.[24]
Unique sebaceous glands[edit]
During the last three months of fetal development, the sebaceous glands of
the fetus produce vernix caseosa, a waxy white substance that coats the skin
to protect it from amniotic fluid.[25]
The areolar glands are in the areola that surrounds the nipple in the female
breast. These glands secrete an oily fluid that lubricates the nipple, and also
secrete volatile compounds that are thought to serve as an olfactory stimulus
for the newborn. During pregnancy and lactation these glands, also called
Montgomery's glands, become enlarged.[26]
Meibomian glands, in the eyelids, secrete a form of sebum
called meibum onto the eye, that slows the evaporation of tears.[27] It also
serves to create an airtight seal when the eyes are closed, and its lipid quality
also prevents the eyelids from sticking together. The meibomian glands are
also known as tarsal glands, Zeis glands and palpebral glands.[28] They attach
directly to the follicles of the eyelashes, which are arranged vertically within
the tarsal plates of the eyelids.
Fordyce spots, or Fordyce granules, are ectopic sebaceous glands found on
the genitals and oral mucosa. They show themselves as yellowish-
white milia (milk spots).[29]
Earwax is partly composed of sebum produced by glands in the ear canal.
These secretions are viscous and have a high lipid content, which provides
good lubrication.[30]
Clinical significance[edit]
Conditions of sebaceous glands.
Sebaceous glands are involved in skin problems such as acne and keratosis
pilaris. In the skin pores, sebum and keratin can create a hyperkeratotic plug
called a comedo.
Acne[edit]
Main article: Acne
Acne is a very common problem, particularly during puberty in teenagers, and
is thought to relate to an increased production of sebum due to hormonal
factors. The increased production of sebum can lead to a blockage of the
sebaceous gland duct. This can cause a comedo, (commonly called
a blackhead or a whitehead), which can lead to infection, particularly by the
bacteria Cutibacterium acnes. This can inflame the comedones, which then
change into the characteristic acne lesions. Comedones generally occur on the
areas with more sebaceous glands, particularly the face, shoulders, upper
chest and back. Comedones may be "black" or "white" depending on whether
the entire pilosebaceous unit, or just the sebaceous duct, is blocked.
[31]
Sebaceous filaments—innocuous build-ups of sebum—are often mistaken
for whiteheads.
There are many treatments available for acne from reducing sugars in the
diet, to medications that include antibiotics, benzoyl peroxide, retinoids and
hormonal treatments.[31] Retinoids reduce the amount of sebum produced by
the sebaceous glands.[32] Should the usual treatments fail, the presence of
the Demodex mite could be looked for as the possible cause.[33]
Other[edit]
Other conditions that involve the sebaceous glands include:
 Seborrhoea refers to overactive sebaceous glands, a cause of oily

skin [4] or hair.[15]
 Sebaceous hyperplasia, referring to excessive proliferation of the
cells within the glands, and visible macroscopically as small papules
on the skin, particularly on the forehead, nose and cheeks. [34]
 Seborrhoeic dermatitis, a chronic, usually mild form
of dermatitis effected by changes in the sebaceous glands.
[35]
In newborn infants seborrhoea dermatitis can occur as cradle
cap.
 Seborrheic-like psoriasis (also known as "Sebopsoriasis",[36] and
"Seborrhiasis") is a skin condition characterized by psoriasis with an
overlapping seborrheic dermatitis.[2]:193
 Sebaceous adenoma, a benign slow-growing tumour—which may,
however, in rare cases be a precursor to a cancer syndrome known
as Muir–Torre syndrome.[4]
 Sebaceous carcinoma, an uncommon and aggressive cutaneous
tumour.[37]
 Sebaceous cyst is a term used to refer to both an epidermoid
cyst and a pilar cyst, though neither of these contain sebum, only
keratin and do not originate in the sebaceous gland and so are not
true sebaceous cysts. A true sebaceous cyst is relatively rare and is
known as a steatocystoma.[38]
 Nevus sebaceous, a hairless region or plaque on the scalp or skin,
caused by an overgrowth of sebaceous glands. The condition is
congenital and the plaque becomes thicker into adulthood. [39]
 Phymatous rosacea is a cutaneous condition characterized by an
overgrowth of sebaceous glands.[36]
History[edit]
The word sebaceous, meaning "consisting of sebum", was first termed in
1728 and comes from the Latin for tallow.[40] Sebaceous glands have been
documented since at least 1746 by Jean Astruc, who defined them as "...the
glands which separate the fat."[41]:viii He describes them in the oral cavity and
on the head, eyelids, and ears, as "universally" acknowledged.[41]:22–25 viii Astruc
describes them being blocked by "small animals" that are "implanted" in the
excretory ducts[41]:64 and attributes their presence in the oral cavity to apthous
ulcers, noting that "these glands naturally [secrete] a viscous humour, which
puts on various colours and consistencies... in its natural state is very mild,
balsamic, and intended to wet and lubricate the mouth". [41]:85–86 In The
Principles of Physiology 1834, Andrew Combe noted that the glands were not
present in the palms of the hands or soles of the feet.[42]
Other animals[edit]
Example of a gular gland in a male black bonneted bat[43]
The preputial glands of mice and rats are large modified sebaceous glands
that produce pheromones used for territorial marking.[4] These and the scent
glands in the flanks of hamsters have a similar composition to human
sebaceous glands, are androgen responsive, and have been used as a basis
for study.[4] Some species of bat, including the Mexican free-tailed, have a
specialized sebaceous gland occurring on the throat called a "gular gland".
[44]
This gland is present more frequently in males than females, and it is
hypothesized that the secretions of the gland are used for scent-marking. [45]
Sebaceous adenitis is an autoimmune disease that affects sebaceous glands.
It is mainly known to occur in dogs, particularly poodles and akitas, where it
is thought to be generally autosomal recessively inherited. It has also been
described in cats, and one report describes this condition in a rabbit. In these
animals, it causes hair loss, though the nature and distribution of the hair loss
differs greatly.
Σαλικυλικό οξύ
Η χημική δομή του σαλικυλικού οξέως
Το σαλικυλικό οξύ (από λατινικό salix, ιτιά) είναι λιπόφιλο
μονοϋδροξυβενζοϊκό οξύ, ένας τύπος φαινολικού οξέος και ένα β-υδροξυ
οξύ (BHA). Έχει τον τύπο C 7 H 6 O 3. Αυτό το άχρωμο κρυσταλλικό
οργανικό οξύ χρησιμοποιείται ευρέως στην οργανική σύνθεση και λειτουργεί
ως φυτική ορμόνη. Προέρχεται από το μεταβολισμό της σαλικίνης.
Εκτός από το ότι χρησιμεύει ως ένας σημαντικός ενεργός μεταβολίτης
της ασπιρίνης ( ακετυλοσαλικυλικό οξύ ), ο οποίος δρα εν μέρει ως
προφάρμακο προς το σαλικυλικό οξύ, είναι πιθανώς πιο γνωστό για τη χρήση
του ως βασικό συστατικό σε τοπικά προϊόντα κατά της ακμής. Τα άλατα και
οι εστέρες του σαλικυλικού οξέος είναι γνωστοί ως σαλικυλικά.
Συμπεριλαμβάνεται στον κατάλογο βασικών φαρμάκων του Παγκόσμιου
Οργανισμού Υγείας, τα ασφαλέστερα και πιο αποτελεσματικά φάρμακα που
χρειάζονται σε ένα σύστημα υγείας.[1]
Πίνακας περιεχομένων
 1Χρήσεις
o 1.1Φάρμακο
o 1.2Χρήσεις στην κατασκευαστική
o 1.3Άλλες χρήσεις
 2Χημεία και παραγωγή

 3Ιστορία
 4Διατροφικές πηγές
 5Φυτική ορμόνη
 6Παραπομπές
Χρήσεις[Επεξεργασία | επεξεργασία κώδικα]
Φάρμακο[Επεξεργασία | επεξεργασία κώδικα]
Το σαλικυλικό οξύ ως φάρμακο χρησιμοποιείται πιο συχνά για να βοηθήσει
στην απομάκρυνση του εξωτερικού στρώματος του δέρματος. Ως τέτοιο,
χρησιμοποιείται για τη θεραπεία κονδυλωμάτων, ψωρίασης, ακμής,
δερματόφυτων, πιτυρίδας και ιχθύασης.[2][3]
Παρόμοια με άλλα υδροξυοξέα, το σαλικυλικό οξύ είναι βασικό συστατικό σε
πολλά προϊόντα περιποίησης της επιδερμίδας για τη θεραπεία
της σμηγματορροϊκής δερματίτιδας, της ακμής, της ψωρίασης, των κάλων,
των καλαμποκιού, της θυλακική υπερκεράτωση, της ακάνθωσης νιτρικάνων,
της ιχθύωσης και των κονδυλωμάτων.[4]
Χρήσεις στην κατασκευαστική[Επεξεργασία | επεξεργασία κώδικα]
Το σαλικυλικό οξύ χρησιμοποιείται στην παραγωγή άλλων φαρμακευτικών
προϊόντων, συμπεριλαμβανομένου του 4-αμινοσαλικυλικού οξέος, της
σανδουλπιρίδης και της λανετιμίδης (μέσω της σαλεθαμίδης).
Το σαλικυλικό οξύ ήταν ένα από τα αρχικά αρχικά υλικά για την
παραγωγή ακετυλοσαλικυλικού οξέος (ασπιρίνη) το 1897.[5]
Το υποαλικυλικό βισμούθιο, ένα άλας βισμούθιου και σαλικυλικού οξέος, είναι
το δραστικό συστατικό στα βοηθήματα ανακούφισης του στομάχου όπως το
Pepto-Bismol, είναι το κύριο συστατικό του Kaopectate και "εμφανίζει
αντιφλεγμονώδη δράση (λόγω του σαλικυλικού οξέος) και επίσης δρα ως
αντιόξινο και ήπιο αντιβιοτικό ".[6]
Άλλες χρήσεις[Επεξεργασία | επεξεργασία κώδικα]
Το σαλικυλικό οξύ χρησιμοποιείται ως συντηρητικό τροφίμων, βακτηριοκτόνο
και αντισηπτικό.[7]
Το σαλικυλικό νάτριο είναι χρήσιμη πηγή φωτός στο κενό στο φάσμα
του υπεριώδους, με σχεδόν επίπεδη κβαντική απόδοση για μήκη κύματος
μεταξύ 10 και 100 νμ.[8] Φθορίζει στο μπλε στο 420 νμ. Παρασκευάζεται
εύκολα σε καθαρή επιφάνεια ψεκάζοντας ένα κορεσμένο διάλυμα του άλατος
σε μεθανόλη και στη συνέχεια με εξάτμιση.
Η ασπιρίνη (ακετυλοσαλικυλικό οξύ ή ASA) μπορεί να παρασκευαστεί με
την εστεροποίηση της φαινολικής υδροξυλομάδας του σαλικυλικού οξέος με
την ακετυλομάδα από οξικό ανυδρίτη ή ακετυλοχλωρίδιο.
Χημεία και παραγωγή[Επεξεργασία | επεξεργασία κώδικα]
Το σαλικυλικό οξύ έχει τύπο C 6 H 4 (OH) COOH, όπου η ομάδα ΟΗ
είναι όρθο στην καρβοξυλική ομάδα. Είναι επίσης γνωστό ως 2-
υδροξυβενζοϊκό οξύ. Είναι ελάχιστα διαλυτό στο νερό (2 g / L στους 20 ° C °
C).[9]
Το σαλικυλικό οξύ βιοσυντίθεται από το αμινοξύ φαινυλαλανίνη. Στο
φυτό Arabidopsis thaliana μπορεί να συντεθεί μέσω μονοπατιού ανεξάρτητου
από τη φαινυλαλανίνη.
Το σαλικυλικό νάτριο παρασκευάζεται στο εμπόριο με επεξεργασία φαινολικού
νατρίου (το άλας νατρίου της φαινόλης ) με διοξείδιο του άνθρακα σε υψηλή
πίεση (100 atm) και υψηλή θερμοκρασία (115 ° C) - μια μέθοδο γνωστή ως
αντίδραση Κόλμπε-Σμιτ. Η οξίνιση του προϊόντος με θειικό οξύ δίνει
σαλικυλικό οξύ:
Μπορεί επίσης να παρασκευαστεί με υδρόλυση ασπιρίνης (ακετυλοσαλικυλικό

οξύ)[10] ή μεθυλοσαλικυλικού (έλαιο από Gaultheria) με ισχυρό οξύ ή βάση.
Το σαλικυλικό οξύ αποικοδομείται σε φαινόλη και διοξείδιο του άνθρακα στους
200 - 230 °C:[11]
C 6 H 4 OH (CO 2 H) → C 6 H 5 OH + CO 2
Ιστορία[Επεξεργασία | επεξεργασία κώδικα]
Η λευκή ιτιά ( Salix alba ) είναι μια φυσική πηγή σαλικυλικού οξέος.
O Ιπποκράτης, ο Γαληνός, ο Πλίνιος ο Πρεσβύτερος και άλλοι ήξεραν ότι ο
φλοιός της ιτιάς θα μπορούσε να ανακουφίσει τον πόνο και να μειώσει τους
πυρετούς.[12] Χρησιμοποιήθηκε στην Ευρώπη και την Κίνα για τη θεραπεία
αυτών των καταστάσεων.[13] Αυτή η θεραπεία αναφέρεται σε κείμενα από
την αρχαία Αίγυπτο, τη Σουμερία και την Ασσυρία.[14] Οι Τσερόκι και άλλοι
ιθαγενείς Αμερικανοί χρησιμοποιούν εκχύλισμα του φλοιού για πυρετό και
άλλους ιατρικούς σκοπούς.
Το 2014, οι αρχαιολόγοι εντόπισαν ίχνη σαλικυλικού οξέος σε θραύσματα
κεραμικής του 7ου αιώνα που βρέθηκαν στο ανατολικό κεντρικό Κολοράντο.
[15]
Ο Αιδεσιμότατος Έντουαρντ Στόουν, από το Όξφορντσαϊρ της Αγγλίας,
σημείωσε το 1763 ότι ο φλοιός της ιτιάς ήταν αποτελεσματικός στη μείωση
του πυρετού.[16]
Το ενεργό εκχύλισμα του φλοιού, που ονομάζεται σαλικίνη, μετά
το λατινικό όνομα για τη λευκή ιτιά (Salix alba), απομονώθηκε και ονομάστηκε
από τον Γερμανό χημικό Γιόχαν Αντρέας Μπούχνερ το 1828.[17] Μια
μεγαλύτερη ποσότητα της ουσίας απομονώθηκε το 1829 από τον Ανρί
Λερού, Γάλλο φαρμακοποιό.[18] Ο Ραφαέλε Πιρία, ένας Ιταλός χημικός,
μπόρεσε να μετατρέψει την ουσία σε σάκχαρο και ένα δεύτερο συστατικό, το
οποίο στην οξείδωση γίνεται σαλικυλικό οξύ. [19]
Το σαλικυλικό οξύ απομονώθηκε επίσης από το βότανο Filipendula
ulmaria (παλαιότερα ταξινομήθηκε ως Spiraea ulmaria ) από Γερμανούς
ερευνητές το 1839.[20] Ενώ το εκχύλισμά τους ήταν κάπως αποτελεσματικό,
προκάλεσε επίσης πεπτικά προβλήματα όπως γαστρικό
ερεθισμό, αιμορραγία, διάρροια και ακόμη και θάνατο όταν καταναλώθηκε σε
υψηλές δόσεις.
Διατροφικές πηγές[Επεξεργασία | επεξεργασία κώδικα]
Το σαλικυλικό οξύ εμφανίζεται σε φυτά ως ελεύθερο σαλικυλικό οξύ και
καρβοξυλιωμένους εστέρες και φαινολικούς γλυκοζίτες του. Αρκετές μελέτες
δείχνουν ότι οι άνθρωποι μεταβολίζουν το σαλικυλικό οξύ σε μετρήσιμες
ποσότητες από αυτά τα φυτά.[21] Ποτά και τρόφιμα με υψηλή περιεκτικότητα
σε σαλικυλικό περιλαμβάνουν μπύρα, καφέ, τσάι, πολλά φρούτα και
λαχανικά, γλυκοπατάτα, ξηρούς καρπούς και ελαιόλαδο, μεταξύ άλλων.[22] Το
κρέας, τα πουλερικά, τα ψάρια, τα αυγά, τα γαλακτοκομικά προϊόντα, η
ζάχαρη και τα ψωμιά και τα δημητριακά έχουν χαμηλή περιεκτικότητα σε
σαλικυλικό.[23]
Μερικά άτομα με ευαισθησία στα διαιτητικά σαλικυλικά μπορεί να έχουν
συμπτώματα αλλεργικής αντίδρασης, όπως βρογχικό άσθμα, ρινίτιδα,
γαστρεντερικές διαταραχές ή διάρροια, και έτσι μπορεί να χρειαστεί να
υιοθετήσουν δίαιτα χαμηλής περιεκτικότητας σε σαλικυλικά. [22]
Φυτική ορμόνη[Επεξεργασία | επεξεργασία κώδικα]
Το σαλικυλικό οξύ είναι μια φαινολική φυτοορμόνη και βρίσκεται σε φυτά με
ρόλο στην ανάπτυξη των φυτών, τη φωτοσύνθεση, τη διαπνοή, την
πρόσληψη ιόντων και τη μεταφορά.[24] Το σαλικυλικό οξύ εμπλέκεται στην
ενδογενή σηματοδότηση, μεσολαβώντας στην άμυνα των φυτών
έναντι παθογόνων.[25] Παίζει ρόλο στην αντίσταση στα παθογόνα
προκαλώντας την παραγωγή πρωτεϊνών που σχετίζονται με την παθογένεση.
[26]
Συμμετέχει στη συστηματική επίκτητη αντίσταση στην οποία μια παθογόνος

προσβολή σε ένα μέρος του φυτού προκαλεί αντίσταση σε άλλα μέρη. Το
σήμα μπορεί επίσης να μετακινηθεί σε γειτονικά φυτά με το σαλικυλικό οξύ να
μετατραπεί σε πτητικό εστέρα μεθυλοσαλικυλικό. Ο σαλικυλικός μεθυλεστέρας
προσλαμβάνεται από τα στομάτα του γειτονικού φυτού, και μόλις βαθιά στο
φύλλο, μετατρέπεται πίσω σε σαλικυλικό οξύ για να προκαλέσει την
ανοσοαπόκριση.[27]
Νιασίνη
Η χημική δομή της νιασίνης

Η νιασίνη, γνωστή και ως νικοτινικό οξύ, είναι οργανικό μόριο το αποτελεί
μορφή της βιταμίνης Β3 και είναι απαραίτητο θρεπτικό συστατικό για τον
άνθρωπο.[1] Η νιασίνη λαμβάνεται μέσω της διατροφής από μία σειρά
φαγητών με μεγαλύτερες συγκεντρώσεις σε ενισχυμένα τρόφιμα, κρέας,
πουλερικά, κόκκινο ψάρι όπως ο τόνος και ο σολομός και σε μικρότερες
ποσότητες στους ξηρούς καρπούς, τα όσπρια και άλλους καρπούς. Η νιασίνη
ως συμπλήρωμα διατροφής χρησιμοποιείται για τη θεραπεία της πελάγρας, μια
ασθένεια η οποία σχετίζεται με την έλλειψη νιασίνης. Σημεία και συμπτώματα
δερματικές και στοματικές βλάβες, αναιμία, πονοκεφάλους και κόπωση.
Πολλές χώρες απαιτούν την προσθήκη νιασίνης στο αλεύρι σιταριού,
μειώνοντας έτσι τον κίνδυνο πελάγρας.[1][2]
Αν και η νιασίνη και το νικοτιναμίδιο έχουν ταυτόσημη δράση ως βιταμίνες, το
νικοτιναμίδιο δεν έχει την ίδια φαρμακοδυναμική, επίδραση στα λιπίδια ή
άλλες από τις δράσεις της νιασίνης, όπως για παράδειγμα η νιασίνη συνδέεται
με την αμινομάδα και μειώνει τη χοληστερόλη, αλλά ούτε προκαλεί εξάψεις.[3]
[4]
Η νικοτιναμίδη συνιστάται ως θεραπεία της έλλειψης νιασίνης επειδή μπορεί
να χορηγηθεί με τρόπο που δεν προκαλεί εξάψεις, οι οποίες θεωρούνται μία
από τις παρενέργειας της νιασίνης.[5]
Η νιασίνη επίσης είναι διαθέσιμη ως συνταγογραφούμενο φάρμακο.
Ποσότητες οι οποίες ξεπερνούν την συνιστώμενη διατητική πρόσληψη για τις
δράσεις της βιταμίνης μπορούν να μειώσουν τα τριγλυκερίδια και
την λιποπρωτεΐνη χαμηλής πυκνότητας (LDL) στο αίμα, ενώ μπορούν να
αυξήσουν τα επίπεδα της λιποπρωτεΐνης υψηλής πυκνότητας (HDL, γνωστή
και ως καλή χοληστερίνη). Υπάρχουν δύο μορφές, η άμεσης δράσης και η
παρατεταμένης δράσης. Η αρχική δόση είναι 500mg/ημέρα και αυξάνεται με
την πάροδο του χρόνου μέχρι να φτάσει θεραπευτικά επίπεδα. Η δόση μπορεί
να φτάσει μέχρι τα 3000 mg/ημέρα για την άμεσης δράσης και τα 2000
mg/ημέρα για την παρατεταμένης δράσης.[6] Παρά την αποδεδειγμένη
επίδρασή της στα λιπίδια, η νιασίνη δεν έχει βρεθεί να βελτιώνει τον
καρδιαγγειακό κίνδυνο σε ασθενείς που λαμβάνουν ήδη στατίνες.[7] Μια
μελέτη του 2010 υποστήριξε τη νιασίνη ως μονοθεραπεία,[8] αλλά μια
μεγαλύτερης έκταση μελέτη του 2017 βρήκε ότι παρά την μείωση των
επιπέδων λιπιδίων, δεν υπήρξε μείωση της θνησιμότητας από όλες τις αιτίες,
της θνησιμότητας από καρδιαγγειακά, των εμφραγμάτων του μυοκαρδίου και
των θανατηφόρων ή μη εγκεφαλικών επεισοδίων. [9] Επίσης έχει δειχθεί η
νιασίνη να προκαλεί ηπατοτοξικότητα και αυξημένο κίνδυνο για σακχαρώδη
διαβήτη τύπου 2.[9] Οι συνταγές νιασίνης έφτασαν το μέγιστό τους στις ΗΠΑ
το 2009, με 9,4 εκατομμύρια συνταγές, αλλά το 2017 είχαν μειωθεί στις 1,3
εκατομμύρια.[10]
Η νιασίνη έχει χημικό τύπο C6H5NO2 και ανήκει στην ομάδα του
πυριδινεκαρβοξυλικού οξεώς. Ως πρόδρομο μόριο του δινουκλεοτιδίου
αδενίνης νικοτιναμιδίου (NAD) και του φωσφορικού δινουκλεοτιδίου αδενίνης
νικοτιναμιδίου (NADP), η νιασίνη εμπλέκεται στην επιδιόρθωση του DNA.[11]
Medicinal use of terrestrial molluscs (slugs and snails) with

particular reference to their role in the treatment of wounds and
other skin lesions
Abstract
The slime produced by terrestrial molluscs (slugs and snails) has interesting
properties which have been utilized for centuries for the treatment of minor
wounds and other skin disorders such as warts. This paper provides an
introduction to the properties of slug slime and considers its potential value in
modern wound management. It also reports the results of a small study in
which this material was successfully used to treat a longstanding wart. This is
believed to be the first illustrated and fully documented account of the use of
slug slime for this indication.
Introduction
Slugs and snails are terrestrial molluscs which have similar morphology except
that slugs, unlike snails, have no obvious shell, although some species
possess a partial or internal vestigial shell. Widely distributed around the
world, the largest species of slug in the UK, the Ashy-Grey slug (Limax
cinereoniger), can exceed 25 cm in length.
Both slugs and snails secrete visco-elastic slime or mucus which acts both as
an adhesive and lubricant and enables the creatures to adhere to, and glide
over, all types of surfaces including rough or potentially hostile terrain. Mucus
also helps to prevent the creatures from drying out, renders them fairly
unattractive as food for predators,[1] and is also thought to help prevent
infection and facilitate healing.
For centuries snails, and to a lesser extent slugs, have been used both as a
food and as a treatment for a variety of medical conditions. Quave et al.
[2] described how, in southern Italy, the common garden slug, Arion
hortensis, is sometimes swallowed whole as a treatment for gastritis or
stomach ulcers. In America slugs are not thought to be swallowed live in this
way, but a recipe for ‘Slug Syrup’ is recorded on the website of the University
of Saskatchewan. This instructs that a jar be filled with alternating layers of
slugs and sugar. After about a day, when the sugar has ‘dissolved’ the slugs,
the resulting mixture is run through a sieve, after which 1/3 grain alcohol is
added by volume. The site quotes the original authors who recommend the
resulting syrup be used for the treatment of ulcers, bronchitis, asthma,
claiming that it is able to ‘heal these conditions when nothing else will.’[3]
Snail and slug slime have been used sporadically as skin treatments since the
time of the Ancient Greeks; Hippocrates reportedly recommended the use of
crushed snails to relieve inflamed skin and some 20 years ago, the potential
of snail slime was noted by Chilean snail farmers who found that skin lesions
healed quickly, with no scars, when they handled snails for the French food
market. This observation resulted in the production of ‘Elicina’ a Chilean snail
slime-based product. In 2010 ‘Missha’ then launched Super ‘Aqua Cell Renew
Snail Cream’, claiming that its 70% snail extract ‘soothes regenerates and
heals skin’. Snail slime based products are claimed to be the new miracle
face-fixer in the U.S where they are used to treat acne, reduce pigmentation
and scarring, and combat wrinkles.[4]
In the publication cited previously, Quave et al.[5] also described how slugs
are used in Italy to treat dermatological conditions. Mucus collected from a
slug is rubbed onto the skin to treat dermatitis, inflammations, calluses, and
acne, and to promote wound healing. In addition, in a special ritual slugs
themselves are used for the treatment of warts. Mucus from a live slug is
first rubbed onto the wart, and then the slug is hung out in the sunshine to
dry out and die. It is believed that once the slug has dried up, the wart should
as well.[2] The use of slugs for the treatment of warts is not, however,
confined to Italy. Records exist of the use of slug slime in the US and UK
some of which recommended that the slime be collected at certain phases of
the moon to ensure maximum effect.
Evidence of this practice may be found amongst the specimens contained in
the Pitt Rivers Museum in Oxford where a glass specimen jar filled with
alcohol contains a slug impaled on a thorn. Purchased by the Museum in July
1898 from Thomas James Carter of Oxford, it provides hard evidence of a
cure used in several parts of the UK. The label on the jar instructs ‘Go out
alone and find a large black slug. Secretly rub the underside on the warts and
impale the slug on the thorn. As the slug dies the warts will go’. In other
parts of the UK such as Berwickshire, Northumberland and Lancashire, the
museum suggests that the slug is replaced by a snail: ‘Take a black snail, rub
the warts with it, and then suspend it upon a thorn; as the snail melts away,
so will the warts. This must be done nine nights successively, at the end of
which time the wart will completely disappear.’[6]
Snail products may even have a role in orthopaedics. Researchers at Herriot-
Watt University found that the slime of Giant African land snails contains
unusual crystals of calcite. Under adverse conditions the snail will retract into
its shell and produce significant quantities of this slime which dries and
quickly hardens to form the animal’s epiphragm - a protective covering
formed across the opening of the shell when the snails go into periods of
deep rest. The authors postulated that in the long term their observations
could point the way to the development of bone cement based on a natural
process involving inorganic crystals in an organic matrix; a biologically
compatible material which might contribute to mechanisms of bone
healing. [7]
The principal benefits associated with the use of slugs and snails as topical
treatments are therefore associated with the chemical and/or physical
properties of the slime or mucus that they produce in abundance, particularly
when threatened or irritated.
Production and properties of slug mucus relevant to wound healing
The mucus producing cells are located in the epithelium of the skin, both on
the foot and upper surface of the body. Slugs produce at least two types
of mucus; pedal mucus, which is relatively thin and contains about 96-97%
water, and a second form which is produced over the entire body. This tends
to be more thick and sticky. Both types are hygroscopic.[1]
The precursor of slime is initially produced by the slug or snail in the form of
highly hygroscopic grains which are stored within the cells in the form of
granules coated with a protective water resistant membrane which keeps
them dry. These packets only break open after they have been released from
the cell, a process which is thought to be mediated by contact with
extracellular ATP.[8] At this point the granules very rapidly absorb up to 100
times their initial volume of water to form the familiar mucus or slime trail.
Slime is a complex material with non-Newtonian properties. In simple terms,
the slime acts like a solid glue at rest, but liquefies when an adequate stress
(or force) is applied to it - rather like non-drip paint or ketchup. When the
applied stress is removed, the slime quickly re-solidifies. This may have
important implications for its use as skin or wound treatment but slugs and
snails use this property to create ‘pedal waves’ in a process known as
adhesive locomotion. By exploiting this ‘yield-heal’ property, the creature can
keep one part of its foot stuck to a surface whilst the remainder moves
forward.[9][10]
Composition of slug/snail slime
The composition of slime is thought to vary according to species, and it is
believed that it is possible that each may also be able to vary its formulation.
[9]
Mucus consists of a complex mix of proteoglycans, glycosaminoglycans,
glycoprotein enzymes, hyaluronic acid, copper peptides, antimicrobial
peptides, and metal ions.[11] Atomic absorption spectrometry showed that
glue from the slug Arion subfuscus contains substantial quantities of zinc,
iron, copper and manganese. Experimentally it was shown that the addition of
iron or copper to dissolved slug glue causes the proteins to precipitate rapidly
but the addition of zinc had no effect, suggesting that some metal ions play
an important role in gel formation.[12]
The presence within the slime of these complex polymers, may have
particular relevance for wound healing as the literature contains many
references to the importance of these materials in the healing cascade.
Studies have also shown that mucus contains peptides such as mucin which
possess antibacterial activity against both Gram positive and Gram negative
bacteria. These antimicrobial peptides not only act as natural antibiotics, but
also stimulate many elements of the immune system, including barrier repair
and inflammatory cell recruitment. The antibacterial factor from the body
surface of the Giant East African Snail, Achatina fulica, for example, exhibited
highly positive antibacterial activity both for the Gram-positive bacteria,
Bacillus subtilis and Staphylococcus aureus and for the Gram-negative
bacteria, Escherichia coli and Pseudomonas aeruginosa, but this activity was
lost when the material was heated at 75º C for 5 min. The antibacterial
factor of the snail mucus was shown to be a glycoprotein with a molecular
weight of about 160,000.[13]
Slug slime is also said to contain a local anesthetic and for this reason there
are anecdotal accounts of live slugs being used to treat toothache.
These local anaesthetic properties (if confirmed) coupled with the
antimicrobial properties and hygroscopic nature of the slime might offer
significant benefits in the treatment of minor but painful wounds such as
superficial burns in humans.
In the United States a patent has been filed (US2009026349) which describes
the possible use of slug slime as a carrier for therapeutic agents in the
treatment of burns and skin conditions and also as a protective covering for
these and other wounds. Within the patent the inventor described how he
had used slug slime on a painful skin rash and subsequently upon self
inflicted burns deliberately produced with a soldering iron. The slime was said
to form a protective layer which eliminated pain and stayed in place during
showering
Scientific evidence which provides some credible basis for the possible use of
slime in wound management may be found in report published in 2008 [14].
The authors found that slime from Cryptomphalus aspersa (also known as H.
aspersa or the common garden snail) contains antioxidant superoxide
dismutase (SOD) and Glutathione-S-Transferase Activity (GST) activities.
Antioxidants are substances that may protect cells from the damage caused
by unstable molecules known as free radicals or reactive oxygen species.
SODs act as antioxidants and protect cellular components from being oxidized
by reactive oxygen species. The authors also reported that the snail slime
stimulated fibroblast proliferation, extracellular matrix assembly and the
regulation of metalloproteinase activities and concluded that these effects
together provided an array of molecular mechanisms underlying the
secretion’s induced cellular regeneration, thereby supporting its possible use
in repair of wounded tissues. In a subsequent study it was also
demonstrated that the slime increased migration and increased the
expression of cell-cell and cell-substrate adhesion molecules in mammalian
fibroblast and keratinocyte cells[15]
It should be noted that some of these properties are analogous to claims
made for some modern wound management materials.
Slug slime in the treatment of warts: an experimental study
In order to determine if the folklore surrounding the use of slugs for the
treatment of warts had any apparent merit, slug slime was applied to a fairly
large, longstanding filiform wart on the inner thigh that was rubbing on
clothing and therefore scheduled for surgical removal. The wart was
monitored and photographed over time resulting in what is believed to be the
first fully documented and illustrated study of its type.
Methodology
Slime was collected as required by irritating the dorsal surface of a specimen
presumed to be Arion ater, the European black slug, (Figure 1) The slime was
applied to the wart using a simple device designed for the purpose consisting
of a small plastic chamber cut from a strip of plastic previously used to supply
tablets. The apex of the chamber was removed and the plastic cup attached
to a piece of semipermeable polyurethane film to form an island dressing
(Figure 2). The slug slime was placed in the chamber and the dressing
applied to the skin. Four applications of gel were made over a period of about
8 weeks in the same way, with the exception that the plastic chamber was
not deroofed for the final two.
Figure 1 - European black slug Arion aters producing slime
Figure 2 - Slime dressing device
The principal reason that treatment was conducted over an extended period
was to accommodate a family holiday. Short intervals were also left between
applications to monitor any changes that might have occurred in the
appearance of the wart and surrounding skin. Under normal circumstances,
however, it would be preferable to provide frequent and uninterrupted
applications of slime to facilitate or accelerate any possible therapeutic effect.
Results
Details of application dates together with a summary of the clinical
observations at each time point are provided in Figures 3 - 11. During the
course of the treatment, the moist conditions produced by the mucus initially
caused the wart to become hydrated which resulted in an apparent increase
in size of the finger-like projections growing from the surface. As the
treatment progressed, however, these projections were lost and eventually
the location of the wart became virtually indistinguishable from the
surrounding skin.
Discussion
The results of this simple investigation provide convincing evidence that the
use of the slug slime coincided with major changes in the appearance of the
lesion in question, although more comprehensive controlled studies would
obviously be required to make a more definitive statement on the efficacy of
the material for this indication.
The mechanism for the observed response of the wart to the slime treatment
is unclear. It might be that there is a physical effect, simply caused by
changes in the hydration of the stratum corneum produced by the semi-
occlusive nature of the dressing. If this is the case it is postulated that
conventional hydrogel or hydrocolloid dressings should prove to be equally
efficacious, and this might in part explain the reported success of other
folklore treatments involving banana skin or potato peelings which might
produce a similar effect.
A more interesting and exciting possibility, however, is that the slime is
exerting some biological effect. Warts are growths resulting from an infection
caused by human papilloma virus and it is interesting to speculate whether
the slime has specific antiviral activity.
Although references have been identified that refer to antiviral activity of
mucins found in the mucous linings of the stomachs of pigs, no references
have been identified which specifically attribute this property specifically to
mucus produced by terrestrial molluscs.
It would not be surprising if such properties did exist however, for slugs (and
to a lesser extent snails) have a moist skin and live an in environment heavily
contaminated with potential pathogenic agents, and thus might be considered
to be at particular risk of developing infections. Mucus, like that present in the
nasal passages of mammals for example, functions as a selectively permeable
replaceable physical barrier between the host and the outside world. If slug
mucus possesses antiviral properties in addition to its antibacterial effects, its
effectiveness in this regard will presumably be greatly enhanced.
If such activity is present, it could provide an explanation for the apparent
ability of slugs to help remove warts and perhaps potentially even treat other
viral skin lesions such as those caused by Herpes simplex.
Irrespective of any possible antiviral activity, slug mucus appears to offer
some real potential benefits in wound management. The results of the
biochemical studies cited previously provide scientific support for a possible
beneficial effect on the proliferation of fibroblasts and keratinocytes which
could contribute directly to enhanced healing. The physical properties of the
mucus may also be important in that it adheres well to human skin even in
the presence of water as any gardener will confirm, and in this regard may
well out-perform most existing hydrogel products. Together all these
observations suggest a number of intriguing possibilities for the production of
new dressing formulations that could represent a promising area for future
research.
The use of slugs and snail is not without risk, however, as these can
sometimes act as vectors of disease. E.coli and other bacteria present in their
faeces have a relatively long external and internal survival time. Slugs and
snails can also become a vector of rat lungworm a disease caused by a
parasitic worm Angiostrongylus cantonensis. Normally carried by rats, the
molluscs become infected by consuming the infected faeces of carrier rats.
The parasite develops further in the slugs and snails and if the infected
molluscs are consumed in turn by rats the life cycle is completed[16]
A. cantonensis generally poses relatively little threat to humans as infections
are very rare, although they can occur from consumption of undercooked or
raw infected slugs and snails either by design or by consuming produce that
has not been adequately washed and therefore contains a small slug or a
snail. The fresh slime of snails and slugs can also have lungworms, which may
be passed on to humans and other animals, although the risks are probably
lower with dry slime as outside of hosts the lungworm dies quickly.
Lungworms are dangerous because once ingested they first head to the brain
where they can cause meningitis type symptoms, with damage to brain tissue
and swelling of the brain before the lungworm dies. Many people show no
symptoms at all before the lungworm dies but others are greatly affected. In
Sydney in 2011 one baby girl died due to lungworm infection and adults have
had severe brain injuries after eating slugs. This small number of cases
suggests that the risk of infection is possibly low, although the consequences
can be disastrous.
Conclusions
The results of the brief literature review identify some intriguing possibilities
concerning the potential value of slug secretions in the treatment of wounds.
These findings, together with the results of the simple study involving the
treatment of a wart, provide some support for empirical observations made in
different parts of the world which led to the use of these materials for medical
purposes. Whilst it is true that in some instances these treatments also
involve a degree of magic or superstitious ritual, this does not of itself mean
that they have no scientific merit.
Indeed, a direct parallel exists to the use of maggots, leeches, bees and bee
products, all of which were used for centuries before the actual mechanisms
of action were clearly defined or understood.
Whilst the plant kingdom has long been recognized as a key source of
medical products, rather less attention has been focused upon members of
the animal kingdom in this regard.
Perhaps in the future it could be the turn of the humble slug to slither quietly
into the medical spotlight by providing a new treatment for wounds which
incorporates agents that accelerate healing whilst providing a degree of
antisepsis and local analgesia.
Figure 3 - Wart prior to application of slime, note characteristic finger-like

projections. 5/8/2012
Figure 4 - Wart after 24 hours treatment, after one day the wart seems more
hydrated and some of the finger-like projections appear to be lost. 6/8/2012
Figure 5 - Wart prior to second application of slime 24 hours later, many of
the finger-like projections appear to have been lost as the wart dried out after
removal of the slime. 7/8/2012
Figure 6 - Wart following removal of second application of slime, shows

rehydration of remaining projections. 8/8/2012
Figure 7 - Wart prior to third application of slime nearly two weeks later, it is
greatly reduced in bulk compared with initial appearance but some evidence
of structure still remaining. 20/8/2012
Figure 8 - Wart after removal of third application of slime, evidence of
rehydration as before. 21/8/2012
Figure 9 - Wart prior to fourth application about 5 weeks later, there is some
evidence of the structure still detectable. 3/10/2013
Figure 10 - Wart covered with slime following removal of dressing two days
later. Note cohesive nature of gel and the healthy appearance of the
surrounding skin. 5/10/2012
Figure 11 - Area following removal of gel residue. Little evidence of the
presence of the wart now detectable. 5/10/2012
Enzyme-processed Korean Red Ginseng extracts protects against skin damage

induced by UVB irradiation in hairless mice
Eunson Hwang,1 Zheng-wang Sun,1 Taek Hwan Lee,2 Heon-Sub Shin,1 Sang-
Yong Park,1 Don-Gil Lee,1 Byung-Goo Cho,3 Hyunjoo Sohn,4 Oh Wook
Kwon,5 Sun Yeou Kim,6,7,* and Tae Hoo Yi1,*
Author information Article notes Copyright and License information Disclaimer
This article has been cited by other articles in PMC.
Abstract
Go to:
INTRODUCTION
Aging is a biological process that changes structural integrity and
physiological function [1]. Skin exposure to UV radiation, particularly its UVB
component (280 to 320 nm), results in photoaging characterized by
pigmentation, roughness, dryness, wrinkle formation, variable epidermal
thickness, and disruption of the epidermal barrier [2]. Photoaging is triggered
by reactive oxygen species as well as the transcription factor activator protein
(AP-1) [3]. Increased expression of AP-1 activates the transcription of matrix-
degrading metalloproteinases (MMPs), which are a zinc-dependent
endoproteases responsible for collagen degradation [4]. In particular, MMP-1
inhibits the synthesis of major dermal collagens by blocking the activity of
transforming growth factor (TGF)-β, which in turn enhances transcription of
collagen genes [5,6]. Dermal fibroblasts form precursor molecules called
procollagen, which are converted into collagen. Further, collagen fragments
negatively regulate the synthesis of new collagen [7]. Therefore, due to the
process of constant degradation of procollagen mediated by MMPs, collagen
production is reduced in photoaged skin.
UVB radiation alters epidermal morphology by increasing and unbalancing
stratum corneum (SC) thickness [8], and such disorganization of the SC
permeability barrier can increase trans-epidermal water loss [9]. Several
studies have investigated the histological and functional responses of the
epidermis to UV irradiation [7,10], including loss of water-holding
properties [9]. Filaggrin and profilaggrin are essential for maintaining
homeostasis in the epidermis. Filaggrin also undergoes further processing in
the upper SC to release free amino acids that assist in water retention [11].
However, little is known about the relationship between wrinkle formation and
epidermal hydration related proteins.
Panax ginseng Meyer has been widely used as a traditional oriental medicine
for various diseases, including atherosclerosis, liver dysfunction,
cerebrovascular disease, hypertension, and post-menopausal disorder [12].
The main pharmacologically active components of ginseng are believed to be
ginsenosides, which are derivatives of triterpene dammaranes [13] and
possess anti-oxidant, antistress, anticancer and pro-immune properties [14-
17]. Commonly available ginseng is divided into fresh, white, and red ginseng.
White ginseng is a powerful herb that stimulates the body’s systems and
helps to reduce stress, boost energy and sustain body fuctions [18]. Red
ginseng is prepared by steaming and drying and can be kept for long periods
of time without loss of its biological activities. Red ginseng extracts have also
been shown to be effective for treating atopic suppurative dermatitis,
wounds, and skin inflammation [19-21]. This research has focused mostly on
dermatological application of ginseng in cosmetics and medicines. On the
other hand, our research is partially conducted in vivo for the purpose of
exploring its application in functional foods. Furthermore, the protective
effects of oral administration of Korean Red Ginseng extract treated with
enzyme (KRGE) against skin photoaging from UVB irradiation have not been
reported. In this study, we investigated whether KRGE prevents UVB
irradiation-induced photodamage in aging hairless mice skin.
Go to:
MATERIALS AND METHODS
Materials
Six-year-old Korean Red Ginseng (KRG) was provided by Dr. Byung-Goo Cho
(R&D Headquarters, Korea Ginseng Corporation, Daejeon, Korea). Standard
ginsenosides, including the compounds Rg1, Re, Rf, Rh1, Rg2, Rb1, Rb2, Rc,
Rd, Rg3, Rh2, and F2 were purchased from Ambo Laboratory (Daejeon,
Korea). All other chemicals were of analytical grade and obtained from local
suppliers.
Preparation of Korean Red Ginseng extract treated with enzyme
KRGE was obtained with its patented protocol (Korea patent no. 10-2011-
0091287 [in private], in press). Briefly, the crude enzyme was extracted
from Aspergillus niger (KACC 40280) which was isolated from the Nuruk for
Korean traditional wine. Then the active enzyme was purified by loading into
an ion-exchage resin. The dried and grinded KRG (0.5 kg) was incubated with
the enzyme solution containing ginsenoside-β-glucosidase and extracted from
5.0 L of ethanol. KRG had reacted with the enzyme at 50℃ to 60℃ for 24 h.
After reaction, the enzyme was removed by ultrafiltration (MWCO, 10,000
Da). Then the solution was filtered and concentrated.
Ultra performance liquid chromatography-photodiode array analysis
Ultra performance liquid chromatography (UPLC) was performed on a Waters
ACQUITY UPLC system (Waters, Mildford, MA, USA) equipped with a binary
solvent delivery system, an autosampler and a UV detector. Chromatographic
separation was performed on a Waters Acquity HPLC BEH C18 column (50×2.1
mm internal diameter, 1.7 μm particle size). The elution was performed by an
acetonitrile/water gradient containing 0.1% formic acid. Runs were carried
out in isocratic mode at a flow rate of 0.6 mL/min. Total run time, including
re-equilibration of the column to the initial conditions, was 27 min. Samples of
2 μL were injected into the UPLC system. The detection range of the
photodiode array detector was set between 190 and 500 nm.
Animals
Seven-week-old male albino hairless mice (SKH: HR-1) (20-27 g; n=40) were
obtained from Central Lab Animals (Seoul, Korea). The experimental protocol
for this study (KHUASP(SU)-12-09) was approved by the Institutional Animal
Care and Use Committee of Kyung Hee University. Mice were housed in a
temperature- and humidity-controlled room (22±1℃, 60±5% humidity) with
12 h light/ dark cycles. After 1 wk of quarantine, mice were acclimated to
individual cages.
UV irradiation
The UV source was supplied by a closely spaced array of five Sankyo Denki
sunlamps, which have a peak irradiance at 310 nm (G9T5E lamps; Sankyo
Denki, Hiratsuka, Japan). Bulbs were positioned 15 cm above the mice.
Irradiance (0.1 mW/cm2) was measured with an IL1700 Research Radiometer
(International Light, Newburyport, MA, USA) equipped with a UVB sensor.
Mice were exposed to 100 mJ/cm2 UVB radiation (1 minimal erythematal
dose=100 mJ/cm2) seven times per week for the first week, and thereafter at
200 mJ/cm2 twice a week for 9 wk. UVB irradiation was applied to the dorsal
skin of mice and no injury to the dorsal skin was observed with the doses of
UVB irradiation administered in this study.
Diet
We randomly divided 40 hairless mice into four groups of ten mice per cage:
1) normal (control diet only), 2) control (UVB irradiation + control diet), 3)
KRGE 0.06% (UVB irradiation + diet containing 0.06% KRGE), and 4) KRGE
0.24% (UVB irradiation + diet containing 0.24% KRGE). All of the mice were
fed solid formula feed. During the experimental period, access to food and
water was provided ad libitum. Animals in each group received the
experimental diets for 10 wk concurrent with the UVB irradiation regimen.
The compositions of the experimental diets given to each group are shown
in Table 1. The amount of dietary fat (supplied as corn oil) was fixed as 10%
of the dietary weight. Food intake and body weight were measured once a
week for all groups.
Table 1.
Composition of diet (g/kg dry diet)
Experimental groups
Normal UVBcont KRGE 0.06% KRGE 0.24%

(n=10) (n=10) (n=10) (n=10)
Casein 230 230 230 230
L-cystine 3 3 3 3
Corn oil 100 100 100 100
Cellulose 50 50 50 50
Vitamin mix 10 10 10 10
Mineral mix 35 35 35 35
Sucrose 200 200 200 200
Corn starch 372 372 371.4 369.6
KRGE - - 0.6 2.4
UVB × ○ ○ ○
irradiation
Group normal, control diet only; group UVBcont, UVB irradiation + control
diet; group Korean Red Ginseng extract treated with enzyme (KRGE) 0.06%,
UVB irradiation + diet containing 0.06% KRGE; group KRGE 0.24%, UVB
irradiation + diet containing 0.24% KRGE; × means non-UV irradiated hairless
mice and ○ means UV irradiated hairless mice.
Wrinkle measurement
To obtain skin replicas, 1.5 g of light-bodied silicone (SilfloR; Flexico,
Colchester, UK) was prepared from two components mixed at a ratio of 1:1
(one drop each of catalyst and thinner). The mixture was then applied to the
skin surface. After drying and hardening, replicas were subjected to further
analysis. The visiometer technique was used to detect changes in the
transparency of thin silicone gel prints of skin surfaces and collected with a
charge-coupled device video camera. Under our conditions, the angle of
incidence of light was fixed at 45℃ relative to the skin replica surface, and
the resulting black and white images were recorded to produce an image file.
The image files were analyzed using Skin Viscometer SV 600 software
(Courage & Khazaka, Cologne, Germany). Arbitrary units (R1 to R5) were
assigned to each sample based on measurements of the depth of furrows
according to shadow size and brightness due to inflection under illumination.
Skin roughness (R1) was defined as the difference between the highest crest
and lowest furrow. To exclude the possibility of artifacts, the program cut
each line into five equal parts, with R3 representing an average of the
maximum distance (R1) derived from each of the five parts of the line.
Likewise, R2 represented the largest value of the five distances while R4
represented the mean area surrounded by a horizontal line drawn at the
highest crest and the furrows profile. R5 was taken as the mean deviation of
the furrow’s profile to the middle line.
Measurement of physiological skin functions
During the study, erythema values and water content of the SC were
measured after feeding and irradiation with an analytical system and
appropriate probes (DermaLab Combo; Cortex Technology, Hadsund,
Denmark). Erythema values and SC hydration levels in the dorsal skin surface
of the hairless mice were measured as described above.
Histological analysis
Mice were sacrificed after the final UVB exposure and biopsies were obtained
from the dorsal skin. Biopsies were fixed in 4% paraformaldehyde for 24 h
and embedded in paraffin. Sections approximately 4 μm thick were stained
with hematoxylin for 10 min, washed, then stained with eosin for 2 min. After
washing with water, the slides were gradually dehydrated in 50%, 70%,
90%, and 100% ethanol. Other samples were stained with Masson’s
trichrome to examine collagen density in the dermis. These sections were first
stained with Bouin solution at 56℃ for 1 h, followed by washing and then
staining with Weigert’s iron hematoxylin working solution for 10 min. Slides
were subsequently washed and differentiated in phosphomolybdic-
phosphotungstic acid solution for 10 to 15 min, then stained with an aniline
blue solution for 5 to 10 min. After washing, the slides were quickly
dehydrated using sequential washes with 95% and 100% ethanol. Stained
slides were examined with a light microscope.
Western blot analysis
Western blotting was performed using total cell and tissue lysates. Following
treatment, cells were harvested and washed in phosphate buffered saline.
Cell and tissue samples were homogenized with lysis buffer containing 50 mM
Tris-Cl, pH 8.0, 0.1% sodium dodecyl sulfate (SDS), 150 mM NaCl, 1%
Nonidet P-40, 0.02% sodium azide, 0.5% sodium deoxycholate, 100 μg/mL
phenylmethylsulfonyl fluoride, 1 μg/mL aprotinin, and a phosphatase inhibitor.
The lysates were then subjected to centrifugation at 12,000 g for 20 min. All
cell and tissue lysates were analyzed in triplicate. Protein concentrations were
measured using Bradford reagent (Bio-Rad, Hercules, CA, USA) with bovine
serum albumin as the standard. Skin tissue lysates containing equal amounts
of total protein were separated by 8% or 10% SDS-PAGE and then
transferred to a nitrocellulose membrane (Amersham Pharmacia Biotech,
Buckinghamshire, UK). Next, membranes were blocked with a solution
containing 5% non-fat milk in tris-buffered saline with tween 20 (TBST) for 1
h at room temperature and then incubated overnight with a primary antibody
at 4℃. The membranes were then washed three times with TBST and
incubated with secondary antibodies (Santa Cruz Biotechnology, Santa Cruz,
CA, USA) for 1 h at room temperature. Finally, immune complexes were
detected with an ECL Western blot detection system (LAS-4000; Fujifilm,
Tokyo, Japan). Densitometry analysis of bands was performed with
ImageMaster 2D Elite software, version 3.1 (Amersham Pharmacia Biotech,
Piscataway, NJ, USA).
Statistical analysis
The results were determined using the Statistical Analysis System (GraphPad
Prism 5). All experiments were carried out in triplicate. The data are
expressed as means±standard deviation. Statistical comparisons between
different treatment groups were performed using one-way analysis of
variance followed by Duncan’s test. Student’s t-test was used to compare
individual treatments to controls. The level of statistical significance was set
at p<0.05.
Go to:
RESULTS
Identification of Korean Red Ginseng extract treated with enzyme composition
As shown in Table 2, the total ginsenoside contents of KRGE was 15.05 mg/g.
The protopanaxadiol and protopanaxatriol ginsenosides contained about 6.20
mg/g and 8.85 mg/g, respectively. Rb1 and Rg1 are the two main
ginsenosides concluded in KRGE (0.39 mg/g and 2.05 mg/g, respectively).
The β-glycosidase from Aspergillus sp. exploits the hydrolytic pathways. The
ginsenoside Rb1, Rb2, or Rg3 transformed into F2, and then Rh2. Because
these β-d-glycosidases are able to simultaneously hydrolyze, they produce the
minor ginsenosides with a high yield, several major ginsenosides [22].
Similarly, our data has been shown that F2 content (3.45 mg/g) showed the
highest level in KRGE.
SimiTable
Ginsenoside contents of Korean Red Ginseng extract treated with enzyme
Ginsenoside Concentration (mg/g)

s
PPT Rg1 2.05
Re 2.96
Rf 0.12
Rh1 0.59
Rg2 0.48
Total 6.20
PPD Rb1 0.39
Rb2 0.96
Rc 0.81
Rd 2.81
Rg3 0.43
Rh2 ND
F2 3.45
Total 8.85
Total 15.05
The ginsenosides of Korean Red Ginseng extract treated with enzyme was
analyzed, ultra performance liquid chromatography was accomplished as in
materials and methods.
PPT, protopanaxatriol; PPD, protopanaxadiol; ND, non-detectable.
Body weight gain and food efficiency rate
The average body weight differences among the four groups of mice were not
significant after 10 wk. During the 3rd week, the mean body weight of the
UVB control group was about 27 g, which was remarkably lower when
compared with the normal group, (29 g). However, the body weights of the
UVB control and normal groups were similar to each other after 8 wk. The
average body weights of the KRGE 0.06% and KRGE 0.24% groups increased
to 31 g (Fig. 1).
Fig. 1.
Weight gain of hairless mice fed control diet only (normal), UVB-
irradiated hairless mice fed control diet (UVBcont), UVB-irradiated
hairless mice fed containing 0.06% Korean Red Ginseng extract
treated with enzyme (KRGE 0.06%) and UVB-irradiated hairless
mice fed containing 0.24% KRGE (KRGE 0.24%) for 10 wk. Values
are mean±SD (10 wk, n=10).
The food efficiency rate (body weight [g]/food intake [g]×100) of the UVB
control group was the lowest (33.87±3.75) among the four groups, while the
food efficiency rates of the other groups were not significantly different from
that of the control group (normal: 36.90±3.30, KRGE 0.06%: 35.43±5.38,
and KRGE 0.12%: 37.99±6.13) (Table 3).
Table 3.
Food efficiency ratio of experimental groups in 10 wk
Dietary group
Normal UVBcont KRGE KRGE 0.24%

0.06%
FER1) 36.90±3.30 33.87±3.75 35.43±5.38 37.99±6.13
Group normal, control diet only; group UVBcont, UVB irradiation + control
diet; group Korean Red Ginseng extract treated with enzyme (KRGE) 0.06%,
UVB irradiation + diet containing 0.06% KRGE; group KRGE 0.24%, UVB
irradiation + diet containing 0.24% KRGE.
1)
FER (food efficiency rate)=gain of body weight (g)/amount of food intake
(g)×100. Values are mean±SD (n=10). Mean with different letters
differ p<0.05.
Wrinkle measurement and analysis of skin replicas
Fig. 2 shows the replicas of the central dorsum of mice. In the non-irradiated
group, the skin appeared to be fine with thin wrinkle formation (Fig. 2A).
Conversely, deeper and wider wrinkles were observed in the UVB-irradiated
control group. The KRGE 0.06% and KRGE 0.24% groups exhibited reduced
UVB-induced wrinkle formation (Fig. 2B). However, no differences were
observed between the KRGE 0.06% and KRGE 0.24% groups (Fig. 2C).
Open in a separate window
Fig. 2.
Features of hairless mice dorsal skin (A), photographs of replicas (B)
and replica analysis (C) taken from the dorsal skin of the mice.
Normal (control diet only), UVBcont (UVB irradiation + control diet),
Korean Red Ginseng extract treated with enzyme 0.06% (UVB
irradiation + diet containing 0.06% KRGE), and KRGE 0.24% (UVB
irradiation + diet containing 0.24% KRGE). Values are mean±SD
(n=5). The data were evaluated for statistical significance with one-
way ANOVA followed by Duncan’s multiple range test. Means with
the same letter are not significantly different. Thus, means with the
different letter, e.g., ‘a’ or ‘b’ are statistically different.
Inhibition of UVB-induced histological changes following oral administration of
Korean Red Ginseng extract treated with enzyme
Red ginseng extract has been reported to prevent UVB irradiation-induced
skin photoaging [23]. In our study, H&E staining showed that KRGE inhibited
increased epidermis thickness caused by UVB irradiation. Likewise, expansion
of skin thickness induced by UVB irradiation appeared to be reversed by
KRGE. Compared with the KRGE 0.24% group, KRGE 0.06% group was more
effective (Fig. 3A).
Fig. 3.
Photomicrographs of H&E-stained sections (A), and
photomicrographs of Masson’s trichrome-stained sections (B) from
the dorsal skin of hairless mice. Normal (control diet only), UVBcont
(UVB irradiation + control diet), Korean Red Ginseng extract treated
with enzyme 0.06% (UVB irradiation + diet containing 0.06%
KRGE), and KRGE 0.24% (UVB irradiation + diet containing 0.24%
KRGE).
Masson trichrome staining was used to observe collagen fibers. Compared
with the normal group, the UVB control group exhibited decreased abundance
and density of collagen fibers. Treatment with KRGE significantly restored the
reduction of collagen fibers induced by UVB-irradiation. Furthermore, dietary
KRGE at a low dose (0.06%) appeared to be more effective at restoring
collagen fibers compared with 0.24% KRGE (Fig. 3B).
Physiological analysis of mouse skin surface following oral administration of
Korean Red Ginseng extract treated with enzyme
Physiological aspects of mouse dorsal skin surfaces after oral administration
of KRGE were analyzed based on data obtained after 4 and 8 wk of UVB
irradiation using an analytical system. The erythema index (EI) and water
contents of the SC are shown in Fig. 4A and and4B,4B, respectively.
Fig. 4.
Under the standardized room conditions of 22℃ to 24℃ and 55% to
60% humidity, erythema index (A) stratum corneum (SC) hydration
(B) of the hairless mice at the end of 10 wk. Values are
means±SD. # and * indicate significant differences (p<0.05)
between the UV (-) control and UV (+) control,
respectively. ##p<0.01 vs. the normal control, *p<0.05 and
***p<0.001 vs. UVB-irradiated control. KRGE, Korean Red Ginseng
extract treated with enzyme.
EI was significantly elevated by UVB exposure (up to 168%) while dietary
KRGE caused a decline in EI. Compared with the UVB control group, KRGE
0.06% (down to 22%) was more efficient in decreasing EI than KRGE 0.24%
(down to 16%). We also measured stratum corneum hydration (SCH). As
shown in Fig. 4B, UVB suppressed SCH while both the KRGE 0.06% and KRGE
0.24% groups exhibited increased SCH by 133% and 111%, respectively.
Further, compared with the KRGE 0.24% group, the SCH levels of the KRGE
0.06% group were much higher.
Changes in MMP-1, procollagen type I, TGF-β1, profilaggrin, and filaggrin
expression following oral administration of KRGE
The mechanisms underlying the beneficial effects of KRGE were investigated
at the level of protein expression. Specifically, we analyzed the expression of
MMP-1, procollagen type I, and TGF-β1. UVB irradiation decreased the
abundance of procollagen type I and TGF-β1 by 69% and 30%, respectively,
but dietary administration of KRGE reversed this effect in UVB irradiated mice.
Furthermore, mice exposed to UVB and a diet containing 0.06% KRGE
exhibited greatly increased expression of procollagen type I and TGF-β1
protein expression (up to 479% and 175%, respectively) compared with UVB
control group (Fig. 5D). In the case of MMP-1, UVB increased protein
expression by 169%, while KRGE reversed this effect. Similar to procollagen
type I and TGF-β1, the reversal of UVB-induced expression of MMP-1 was
more prominent in the KRGE 0.06% group than the KRGE 0.24% group (Fig.
5A).
Fig. 5.
The protein expressions of matrix-degrading metalloproteinase
(MMP)-1, procollagen type I and transforming growth factor (TGF)-
β1 (A) in the dorsal skin; filaggrin and profilaggrin in epidermis (B)
and in dermis (C) of hairless mice. The signal intensities from
multiple experiments (D-F) were quantified, and the integrated
areas were normalized, first to the corresponding value of α-tubulin
and then to the signal observed in the normal group. The bar graphs
(n=3) represent quantitative densitometric results of upper bands.
Values are means±SD. # and * indicate significant differences
(p<0.05) between the UV (-) control and UV (+) control,
respectively. #p<0.05 and ##p<0.01 vs. the normal control, *p<0.05,
**p<0.01, and ***p<0.001 vs. UVB-treated control. KRGE, Korean
Red Ginseng extract treated with enzyme.
Profilaggrin and filaggrin were measured in both the epidermis and dermis by
Western blot with α-tubulin as an internal reference. The expression of
profilaggrin and filaggrin was clearly higher in the epidermis compared with
the dermis. UVB exposure decreased expression of profilaggrin and filaggrin
in both the epidermis and dermis, which was reversed by KRGE (Fig. 5B, C,
respectively). Similar to the aforementioned effects of KRGE, the KRGE 0.06%
group exhibited more significant changes than the KRGE 0.24% group (Fig.
5E, F).
Go to:
DISCUSSION
MMPs play a primary role in the pathophysiological mechanism of
photoaging [4]. Activated MMP-1, a member of the collagenase MMP
subfamily, triggers collagen degradation. Specifically, activated MMP-1
degrades collagen type I, a primary component of the extracellular matrix,
which itself is a source of structural support in the dermis [24]. As reported
previously, UV irradiation increases the expression of AP-1, which in turn
interferes with the synthesis of collagen type I by blocking TGF-β
signaling [25,26]. In the present study, decreased expression of both TGF-β1
and procollagen type I due to UVB irradiation was significantly restored when
KRGE was administered. Specifically, KRGE markedly attenuated MMP-1
expression and increased expression of both TGF-β1 and procollagen type I in
skin tissue, with the KRGE 0.06% group exhibiting stronger effects than the
KRGE 0.24% group. Given that a lower concentration of KRGE was more
beneficial than higher doses, it will be important in future studies to
determine an optimal dose of KRGE. Similarly, as we did not analyze the
effect of KRGE on UVB-mediated changes in AP-1 expression, this should also
be evaluated in future studies.
The SC is known as a barrier that protects underlying tissue from infection,
dehydration, and exposure to chemical insults and mechanical stress. Within
the SC, filaggrin monomers can become incorporated into lipid envelopes,
which are responsible for the skin barrier function. In addition, filaggrin
undergoes further processing in the upper SC to release free amino acids that
assist in water retention [10,11]. In the present study, the results show that
KRGE reversed the inhibitory effects of UVB irradiation on filaggrin and
profilaggrin production in both the epidermis and dermis (Fig. 5B, C).
Similarly, the results show that skin dryness induced by UVB exposure was
reversed by KRGE, with the SC of the KRGE 0.06% group exhibiting increased
moisture levels (Fig. 4B). Taken together, these results suggested that a low
concentration of KRGE may play a role in restoring xerotic skin induced by
UVB irradiation by increasing the production of both filaggrin and profilaggrin.
We previously investigated the protective effects of dietary KRGE extracts in
UVB-irradiated skin aging in hairless mice, and observed up-regulation of
collagen expression and down-regulation of MMP-1 secretion [23]. Likewise,
Kim et al. [27] reported that dietary red ginseng stimulates epidermal
hydration and ceramide production in UV-irradiated hairless mice. In the
present study, we found that KRGE positively regulated not only collagen and
MMP-1 production, but also epidermal hydration and filaggrin. Although there
have been numerous studies conducted on the effects of red ginseng on skin
anti-aging [23,28,29], to the best of our knowledge there have been no
studies evaluating the effects of low dose dietary KRGE on skin photoaging
and hydration. The major ginsenosides, including Rb1, Rb2, and Rc, as
glycosylated ginsenosides are poorly absorbed into the gastrointestinal
tract [30]. In contrast, the absorption of the minor ginsenosides as
deglycosylated ginsenosides is quite easy in the bloodstream [31]. Enzymatic
transformation technique may be responsible for high absorption of the
ginsenosides by transforming the major ginsenosides to the minor
ginsenosides via the selective hydrolysis of the sugar moieties of
ginsenosides. These may lead that a low dose of KRGE had stronger
protective effects against UVB-induced photodamages than a high dose of
KRGE.
According to the results of the present study, there was no difference with
respect to reduction of visible wrinkle formation between low (0.06%) and
high doses (0.24%) dietary KRGE. However, with respect to histologic,
physiologic, and molecular changes in skin tissue, the protective effects of
KRGE with a low dose of 0.06% dietary KRGE were more significant than that
of high dose KRGE (0.24%). In conclusion, a low dose of KRGE as a dietary
supplement has potential beneficial effects on photoaging. Furthermore, it is
likely that KRGE may have useful effects in both bio-health skin care products
and cosmetics.
Antinociceptive and antiinflammatory effects of Centella asiatica
MN Somchit , MR Sulaiman , A Zuraini , L Samsuddin , N Somchit , DA Israf ,

S Moin
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences,
43400 UPM Serdang, Selangor, Malaysia
Date of Submission 24-Mar-2004

Date of Decision 23-Jul-2004
Date of Acceptance 25-Jul-2004
Correspondence Address:
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences,
43400 UPM Serdang, Selangor, Malaysia
nhareet@medic.upm.edu.my
» Abstract
OBJECTIVE: To evaluate the effects of Centella asiatica (CA) upon pain

(antinociception) and inflammation in rodent models. MATERIAL AND
METHODS: The antinociceptive activity of the water extract of CA (10, 30,
100 and 300 mg/kg) was studied using acetic acid-induced writhing and hot-
plate method in mice. The antiinflammatory activity of CA was studied in rats
by prostaglandin E2-induced paw edema. RESULTS: Water extract of CA
revealed significant antinociceptive activity with both the models. The activity
was statistically similar to aspirin but less potent than morphine. The CA
extract also revealed significant antiinflammatory activity. This effect was
statistically similar to the non-steroidal antiinflammatory drug, mefenamic
acid. CONCLUSION: These results suggest that the water extract of CA
possesses antinociceptive and antiinflammatory activities.
How to cite this article:

Somchit M N, Sulaiman M R, Zuraini A, Samsuddin L, Somchit N, Israf D A,
Moin S. Antinociceptive and antiinflammatory effects of Centella asiatica.
Indian J Pharmacol 2004;36:377-80
How to cite this URL:

Somchit M N, Sulaiman M R, Zuraini A, Samsuddin L, Somchit N, Israf D A,
Moin S. Antinociceptive and antiinflammatory effects of Centella asiatica.
Indian J Pharmacol [serial online] 2004 [cited 2020 Dec 15];36:377-80.
Available from: https://www.ijp-online.com/text.asp?2004/36/6/377/13511
» Introduction Top
Centella asiatica (CA) of the family Umbelliferae is commonly found in parts of

India, Asia and the Middle East. It is known as 'Pegaga' in Malaysia, 'Luei
Gong Gen' or 'Tung Chain' in China, 'Vallarai' in Tamil Nadu (India) and 'Daun
Kaki Kuda' in Indonesia.[1] It is a perennial, herbaceous creeper growing up
to 30 cm in height with fan-shaped leaves. CA has been used in traditional
medicine in Asia for hundreds of years.[2] The major constituents are
triterpene saponins, mainly asiaticoside, sapogenin asiatic acid,
madecassoside and madecassic acid.[3] In Malaysia, this herb is commonly
eaten fresh as a vegetable, especially by Malay communities. It is also
believed to have beneficial effects in improving memory, and treating mental
fatigue, anxiety and eczema.[4] Ayurvedic medicine has effectively used CA in
the treatment of inflammation, anemia, asthma, blood disorders, bronchitis,
fever, urinary discharge and splenomegaly.[5]
The aqueous extract of CA possesses antioxidant, cognitive-enhancing and
antiepileptic properties.[6] Although this herb has many useful claims, the
mechanism of its medicinal effects are not understood. The objectives of this
study were to evaluate the antinociceptive and antiinflammatory activities of
CA extract in mice and rats.
» Material and Methods Top
Chemicals
Acetic acid, naloxone hydrochloride, prostaglandin E2 (PGE2), aspirin (ASA),

mefenamic acid (MA) and other standard laboratory chemicals were obtained
from Sigma Chemicals, Dorset, England. All drugs and extracts were dissolved
in normal saline prior to use. Morphine sulfate was generously given by the
Department of Biomedical Sciences, Faculty of Allied Health Sciences, National
University of Malaysia, Kuala Lumpur, Malaysia.
Plant material and extraction
Centella asiatica whole plant was purchased from a local producer in

Selangor, Malaysia and was authenticated by the curator of the phytomedical
herbarium, Institute of Bioscience, Universiti Putra Malaysia. Voucher
specimen (SK 533/03) was deposited in the herbarium. One kg of wet CA was
oven-dried at 50o C for 24 h and ground to powder. The powder was
extracted using distilled water in a Soxlet apparatus according to the
previously published method.[7] The resultant extract was freeze-dried and
kept at -20o C prior to use.
Animals
Adult male ICR Balb/c mice (20-25 g) were used for all the antinociceptive
experiments. Adult male Sprague-Dawley rats (200-250 g) were used to study
the antiinflammatory activity. The animals (five per cage) were maintained
under standard laboratory conditions (light period of 12 h/day and
temperature 27° C ± 2° C), with access to food and water ad libitum. The
experimental procedures were carried out in strict compliance with the
Institutional Animal Ethics Committee regulations. All experiments were
performed in the morning according to the guidelines for the care of
laboratory animals.[8]
Acetic acid-induced writhing
The antinociceptive activity of CA was assessed using writhing test

(abdominal constriction test).[9] Acetic acid solution (10 ml/kg, 0.6%) was
injected intraperitoneally, and the contraction of abdominal muscles together
with stretching of the hind limbs was cumulatively counted over a period of
0.5 h beginning 5 min after acetic acid injection. The extract was
administered (0, 10, 30, 100 and 300 mg/kg, i.p.) 0.5 h before the acetic acid
injection. Antinociceptive activity was expressed as the percentage inhibition
of abdominal constrictions between control animals and mice pre-treated
(n=6) with the extract using the ratio:
(Control mean - Treated mean) x 100 / Control mean
In an attempt to investigate the participation of the opioid system in the

antinociceptive effect of this plant extract, separate groups of mice (n=6)
were pretreated with non-specific opioid receptor antagonist, naloxone (5
mg/kg, i.p.), injected 15 min before the administration of the extract.
Hot-plate test
The hot-plate test was performed to measure response latencies according to

the method previously described.[10] The hot-plate (Model 7280, Ugo Basile,
Italy) was maintained at 55.0 ± 0.2° C and the animals were placed into the
perspex cylinder on the heated surface and the time (sec) to discomfort
reaction (licking paws or jumping) was recorded as response latency, prior to
and 30, 60, 120 and 150 min after administration of the extract (0, 10, 30,
100 and 300 mg/kg, i.p.). A latency period of 20 sec was defined as complete
analgesia and the measurement was terminated if it exceeded the latency
period in order to avoid injury.
PGE2-induced inflammation
Sprague Dawley rats were divided into 5 groups (n=6/group). Groups 1 and 2
were given saline i.p. Thirty min after saline injection the control group
(Group 1) received 0.1 ml of saline at the hind paw and Group 2 received
PGE2 (100 IU) through intraplantar route. Groups 3 and 4 received 2 and 4
mg/kg CA extract (i.p.) respectively. This was followed by the administration
of PGE2 through the intraplantar route. Group 5 received 10 mg/kg
mefenamic acid i.p. prior to PGE2 administration. The paw volume was
measured every 0.5 h for 4 h using the method published previously.[11]
Statistical analysis
Numerical results are expressed as mean±SD, unless otherwise stated. One-

way analysis of variance (ANOVA) was used for statistical comparison; P<0.05
being the criterion for statistical significance. The significant treatment means
were further subjected to Duncan multiple post test.
» Results Top
Effect of CA extract on the acetic acid-induced writhing
As shown in [Table - 1], water extract of CA (10, 30, 100 and 300 mg/kg,
i.p.) showed a significant dose-dependent reduction in the number of writhing
with approximately 13%, 45%, 64% and 85% of inhibition respectively.
Maximum inhibition was observed at the dose of 300 mg/kg, which was
statistically similar to the control drug aspirin (100 mg/kg). Morphine (10
mg/kg) showed the most potent inhibition.
The mechanism of the CA-induced antinociception was investigated using the

opioid receptor antagonist, naloxone. The antinociceptive effect induced by
the aqueous extract of CA (300 mg/kg) was significantly antagonized by
pretreatment with naloxone in the writhing test [Table - 1]. Naloxone also
inhibited the other doses of CA in this test (data not shown).
Effect of CA extract on hot-plate test
[Table - 2] shows the time course of the antinociception produced by the

aqueous extract of CA (0, 10, 30, 100 and 300 mg/kg). Intraperitoneal
administration of the extract resulted in significant and dose-dependent
prolongation of the response latency in the hot-plate test. The effect reached
a peak at approximately 60 min after administration and then gradually
decreased.
Effect of CA extract on PGE2-induced inflammation
The extracts of CA elicited dose-dependent antiinflammatory activity [Table -

3]. At 2 mg/kg concentration, the extract had mild antiinflammatory property.
However, at 4 and 10 mg/kg, the antiinflammatory activity was significantly
different from the control (P<0.05). The antiinflammatory activity of
mefenamic acid was found to be similar to that of the CA (4 mg/kg).
Interestingly, the 10 mg/kg CA showed a significantly higher effect when
compared to mefenamic acid.
» Discussion Top
Administration of CA extracts showed significant antinociceptive activity in the

hot-plate and acetic acid-induced writhing tests [Table - 1] and [Table - 2].
These results indicate that the plant extract possesses centrally and
peripherally mediated antinociceptive properties.[12]
The hot-plate method is one of the most common tests for evaluating the
analgesic efficacy of drugs/compounds in rodents.[13] However, care must be
taken for drugs/compounds that produce false positive results by modifying
the behavior of the rodents.[14] The inhibition of antinociception by
naloxone, an opioid receptor antagonist, in both the hot-plate and abdominal
writhing test revealed these results were positive and the mechanism of CA
antinociception might involve opioid receptors. The potency of antinociception
was less than morphine and aspirin at similar doses.
Intraperitoneal administration of CA reduced the PGE2-induced paw edema
significantly. The extract showed significant antiinflammatory activity even at
2 mg/kg when compared to control and larger dose was found to be more
effective then mefenamic acid. The antiinflammatory activities of various
herbs have been closely related to the high content of triterpenes.[15]
Inamdar et al [3] reported bioactive terpene acids such as asiatic acid and
madecassic acid from the water-methanol extraction of CA. These
phytocompounds may be present in the crude extract of CA that may account
for the antinociceptive and antiinflammatory activities. The results from this
present study strongly indicate that the water extract of CA possesses
antinociceptive and antiinflammatory activities. These findings justify the
traditional use of this plant in the treatment of inflammatory conditions or
rheumatism. Further biological studies using major phytochemicals from CA,
asiaticoside, sapogenin asiatic asid, madecassoside and madecassic acid, are
suggested to determine the active chemical(s) responsible for these activities
of the extract.

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