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THE PHARMACOLOGICAL IMPORTANCE OF CAPSICUM SPECIES (CAPSICUM

ANNUUM AND CAPSICUM FRUTESCENS) GROWN IN IRAQ

Article · January 2015

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Ali Esmail Al-Snafi. / Journal of Pharmaceutical Biology, 5(3), 2015, 124-142.

Journal of Pharmaceutical Biology

www.jpbjournal.com e-ISSN - 2249-7560
Print ISSN - 2249-7579

THE PHARMACOLOGICAL IMPORTANCE OF CAPSICUM

SPECIES (CAPSICUM ANNUUM AND CAPSICUM FRUTESCENS)
GROWN IN IRAQ
Ali Esmail Al-Snafi
Department of Pharmacology, College of Medicine, Thi qar University, Nasiriyah, P O Box 42, Iraq.

ABSTRACT
Capsicum annuum and Capsicum frutescens contained a wide range of nutritional components and
pharmacologically active metabolites. Both species exerted a wide range of pharmacological activities. The present review
will highlight the chemical constituents and the pharmacological and therapeutic effects of Capsicum annuum and Capsicum
frutescens.

Keywords: Capsicum annuum, Capsicum frutescens, Pharmacology, constituents.

INTRODUCTION
Medicinal plants are the Nature’s gift to human exerted a wide range of pharmacological activities. The
beings to help them pursue a disease-free healthy life, present review will highlight the chemical constituents
wide range of pharmacological effects were recorded to and the pharmacological and therapeutic effects of
different medicinal plants [1-46]. Genus Capsicum is a Capsicum annuum and Capsicum frutescens.
member of family Solanaceae and has five species that
are commonly recognized as domesticated: Capsicum SYNONYMS
annuum, Capsicum baccatum, Capsicum chinense, Capsicum annuum
Capsicum frutescens, and Capsicum pubescens. Capsicum annuum var. acuminatum Fingerh.,
Capsicum has its beginning since the beginning Capsicum annuum var. aviculare (Dierb.) D'Arcy &
of civilizations. It is a part of human diet since 7500 BC. Eschbaugh, Capsicum annuum var. conoides (Mill.) Irish,
The genus Capsicum is one of the first plants being Capsicum annuum var. cordiforme Edwall, Capsicum
cultivated in the New World with beans (Phaseolus sp.), annuum var. fasciculatum (Sturtev.) Irish, Capsicum
maize (Zea mays L.), and cucurbits (Cucurbitaceae) [47]. annuum var. grossum (Willd.) Sendtn., Capsicum
In the sixteenth century, Capsicum annuum and annuum var. longum (DC.) Sendtn., Capsicum
Capsicum frutescens were widely distributed from the cerasiforme Mill., Capsicum cerasiforme Willd.,
New World to other continents via Spanish and Capsicum conoides Roem. & Schult, Capsicum
Portuguese traders while the other species are little cordiforme Mill, Capsicum frutescens var.
distributed outside South America [48]. cerasiforme (Mill.) L.H.Bailey, Capsicum frutescens
Only two species C. annuum and C. frutescens var. conoides (Mill.) L.H.Bailey, Capsicum
were grown in Iraq. Shape and color variation of C. frutescens var. fasciculatum (Sturtev.) L.H.Bailey,
annuum is similar with C. frutescens [49]. Capsicum frutescens var. grossum (Mill.) L. H. Bailey,
Capsicum species can be eaten raw or cooked. Capsicum frutescens var. longum (Sendtn.) L. H. Bailey,
Those used in cooking are generally varieties of Capsicum grossum L., Capsicum indicum auct., Capsicum
Capsicum annuum and Capsicum frutescens species [50]. indicum var. aviculare Dierb., Capsicum indicum var.
Capsicum annuum and Capsicum frutescens species conoideum (Mill.) Dierb., Capsicum indicum
contained a wide range of nutritional components and subsp. elaeocarpon Dierb., Capsicum indicum
pharmacologically active metabolites. Both species var. ribesium Dierb., Capsicum longum DC., Capsicum

Corresponding Author:- Ali Esmail Al-Snafi Email:- aboahmad61@yahoo.com

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petenense Standl [51-53].
Capsicum frutescens
Capsicum fastigiatum Blume, Capsicum
annuum L. var. frutescens (L.) Kuntze [54].
Common names
Capsicum annuum
Afrikaan: Rissie; Albanian: Spece, Speci;
Amharic: Yafrank Karya; Arabic: Fulful, Fulful Akhdar,
Fulful Baladi, Fulful Ahhmar, Fulful Halou, Fulaifilah
Halwa; Armenian: Garmir Bghbegh, Karmir Pghpegh;
Azeri: ĺstiot, Qirmizi BibƏr; Austria: Paprika;
Ayurvedic: Raktamaricha, Lankaa, Katuviraa; Basque:
Piperrautsa; Brazil: Pimant, Pimentậo; Breton: Pimant
Dous; Belgium: Peper; Bulgarian: Cherven Piper,
Piperka; Catalan: Pebrotera; Chinese: Chiao-Tzu, Ching
Chiao; English: Chilli, Red Pepper; Farisi: Paprika;
French: Piment Annuel, Gros Piment, Piment Doux;
German: Cayennepfeffer, Chile, Chili, Chilli; Greek:
Pipera, Piperia; Hungarian: Bell
Paprika,Csemegepaprika; India: Molar Gujaarati, Degi
Mirch, Deshi Mirch; Indonesia:Cabai, Cabe, Cabe
Manis; Italian: Peperone, Pepperoncini, Pepperoncino;
Japanese: Bansho, Bapurika, Peppaa; Malaysia: Cabai,
Chili, Cili; Russian: Perets Krasnyj, Perets Zelenyi;
Spanish: Aji, Chile, Chile Jalapento; Turkish: Biber,
Kirmizi Biber, Pul Biber Filfil-e-Ahmar, Filfl-e-Surkh,
Surkh Mirch.; Siddha: Milagay and Unani: Mirch
[51,55].
Capsicum frutescens
Ayurvedic: Katuviraa; Bengali: Gachmirch;
English: Bird Chilli; Gujrati: Mirchi; Hindi: Lalmirch;
Kannada: Menashinakai; Malyalam: Chabbai; Marathi:
Mirchi; Sanskrit:: Katuvira; Siddhal: Musi Milagay;
Sinhalese: Miris; Tamil: Mullagay; Telugu: Mirapakai;
Unani: Surkh Mirch; Urdu: Mirch(55-57).
Family: Solanaceae
Description
Capsicum annuum
Capsicum annuum L. is a small herb that can
grow up to 1 m tall. Leaves are oblong-ovate, ovate, or
ovate-lanceolate, 4–13 cm by 1.5–4 cm with entire
margin. Flowers are small, white or tinged purple. Fruits
are mostly red, but can be green, orange, yellow and can
grow up to 15 cm. Seeds are pale yellow, discoid or
reniform and 3–5 mm [58-63].
Capsicum frutescens
Capsicum frutescens is an annual or short-lived
perennial herb. The stem of Capsicum frutescens almost
striate, glabrous, highiet between 1-4 feet depending on
climate and growing conditions. The leaves are elliptical,
slightly leathery, dark green and smooth, and measure 2½
inches long and 1 inches wide. The flowers are typically
conical or funnel form with five petals, usually fused and
color is white. The fruits are erect, ellipsoid-conical to
lanceoloid, 10-20 mm long, 3-7 mm in diameter. These
fruits have range in color from green when immature to
purple, red, orange or yellow when ripe [64-65].
Distribution
The cultivation of Capsicum (Solanaceae)
originated in Central and South America, with the
Capsicum annuum, C. frutescens, C. baccatum, C.
pubescens and C. Chinense species [66-67]. These species
were spread quickly throughout the subtropical regions
and still grows wild today. The plant grows in tropical
climates, because it needs a warm, humid climate to
survive [68-69].
Traditional uses
Capsicum is a tropical and an important
agricultural crop and one of the popular vegetables, not
only because of its economic value, but also for the
combination of color, taste and nutritional values of its
fruit [70-71]. The interest in the consumption of capsicum
is, to a large extent due to its content of bioactive
compounds and their importance as dietary antioxidants.
Peppers were used fresh, dried, fermented, or as an
oleoresin extract. It has both nutritional and nutraceutical
importance [72].
Capsicum was used as a colourant, flavourant,
and/or as a source of pungency. The main source of
pungency in peppers is the chemical group of alkaloid
compounds called capsaicinoids (CAPS), which are
produced in the fruit. Capsaicin (C18H27NO3), trans-8-
methyl-N-vanillyl-6-nonenamide), is the most abundant
CAPS, followed by dihydrocapsaicin, with minor
amounts of nordihydrocapsaicin, homocapsaicin,
homodihydrocapsaicin, and others. Capsaicin is a white
crystalline, fat-soluble compound formed from
homovanillic acid that is insoluble in water, odourless,
and tasteless [48].
The red colour of mature pepper fruits is due to
several related carotenoid pigments, including capsanthin,
capsorubin, cryptoxanthin, and zeaxanthin, which are
present as fatty acid esters. The most important pigments
are capsanthin and its isomer capsorubin, which make up
to 30–60% and 6–18% respectively, of the total
carotenoids in the fruit [73].
It is also important for its flavor in many
products in addition to its color. Dried chilli is also valued
for its contribution to flavor in chilli sauces and chilli
powders. The flavoring principle is associated with
volatile aromatic compounds and color. As a general rule,
when the color of paprika or chilli powder fades, the
flavor also disappears [72]. Both volatile and non-volatile
substances contribute to its use as flavoring agent [74].
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Capsicum annuum was used traditionally to treat
toothache. The fruits are used to stimulate gastric
activities and increase blood circulation. It is also a
stimulant, carminative, and used locally for neuralgia and
for rheumatism. Uterine pain associated with childbirth is
treated with soup containing the fruit. The Commission E
approved Capsicum annuum for painful muscle spasms in
areas of shoulder, arm and spines. Preparations are used
to treat arthritis, neuralgia, lumbago and chilblains [61,
75-77].
Capsicum frutescens was also used traditionally
as an external therapy in painful muscle spasms in areas
of shoulder, arm and spine; for treating arthritis,
neuralgia, lumbago and chilblains. In addition, it also
used for the treatment of diabetes, blood pressure [high/
low], bronchitis, burning feet, to increase circulation,
relieve rheumatic pain, treat mouth sores and infected
wounds, reduce blood clots, and aid digestion by
stimulating saliva and gastric juice flow [68,78].
Parts used medicinally: fruits.
Physicochemical properties
Capsicum annuum contained total ash 9.27 %,
acid insoluble ash 0.74%, water soluble ash 1.49% , loss
on drying 8.90%, total alcoholic-soluble extractive value
3.54% and total water-soluble extractive value 9.32%
[79].
The physicochemical properties of Capsicum
annuum (Sweet pepper) and Capsicum annuum (Bell
pepper) oils were: refractive index 1.439 ± 0.01 and
1.428 ± 0.00, specific gravity 0.802 ± 0.01 and 0.751 ±
0.01 (g/cm3) , acid value 0.785 ± 0.01 and 1.346 ± 0.10
(mg/g), iodine value 27.920 ± 0.20 and 17.770 ± 0.11
(mg/g) , saponification number (mg/g) 138.250 ± 0.23
and 147.263 ± 0.02 and unsaponifiable matter (mg/g)
1.780 ± 0.11 and 1.890 ± 0.04. While, physicochemical
properties of C. frutescens (Bird eye chilli) and C.
frutescens (Bird pepper) oils were: refractive index
1.428 ± 0.00 and 1.451 ± 0.01, specific gravity (g/cm3)
0.765 ± 0.01 and 0.830 ± 0.01, acid value 1.122 ± 0.10
and 2.693 ± 0.11(mg/g), iodine value 25.380 ± 0.22 and
22.842 ± 0.10 (mg/g), saponification number (mg/g)
117.81 ± 0.30 and 187.935 ± 0.21 and unsaponifiable
matter (mg/g) 1.473 ± 0.05 and 2.400 ± 0.05 [80].
Chemical constituents
Capsicum annuum
The chemical composition of Capsicum annuum
fruits included dry mater (9.92%), total fat (0.33g),
protein (0.99 g), carbohydrate (10.63g), dietary fiber
(2.73g) , vitamin C (133.00mg), calories (46.79cal) and
energy (195.58kj) [81].
Zaki et al., determined the nutritional and
chemical composition of Capsicum annuum powder (dry
weight, DW) at different harvest times (December,
November, October and September). They found that the
nutritional and chemical composition ranged as follow:
carbohydrate (g/100 g DW) 55.33 ± 4.8 - 55.96 ± 3.3,
protein (g/100 g DW) 20.19 ± 2.6 - 21.50 ± 4.5, lipid
(g/100 g DW) 7.55 ± 3.9 - 9.75 ± 3.3, dietary fiber
(g/100 g DW) 35.05 ± 1.4 - 37.07 ± 3 , total sugar (g/100
g DW) 6.88 ± 0.47 - 11.19 ± 0.11, energy content (kJ)
1449.55 - 1573.17, vitamin C (mg/100 g) 1360.2 ± 14.3 -
2020 ± 32.3, total capsaicinoids (mg/kg DW) 24.8 ± 5.5 -
59.7 ± 6.2, Scoville heat value 73-938, potassium
(mg/100 g DW) 2168 ± 147 - 2523 ± 280, phosphorus
(mg/100 g DW) 363 ± 43 - 453 ± 30, magnesium
(mg/100 g DW) 130 ± 15 -146 ± 49, calcium (mg/100 g
DW) 41.62 ± 10 -186 ± 54, iron (mg/100 g DW) 31 ± 10 -
53 ± 15, sodium (mg/100 g DW) 30 ± 4 - 71 ± 9, copper
(mg/100 g DW) 1.06 ± 0.5 - 1.31 ± 0.3 and zinc (mg/100
g DW) 1.67 ± 0.2 - 2 ± 0.2(82). However, Raimi et al., that
the mineral composition of Capsicum annuum (Sweet
pepper) and Capsicum annuum (Bell pepper) oils ranged
as Na 3.40 ±0.01 and 6.10 ±0.01, K 43.70 ±0.13 and
49.10 ±0.06, Ca 8.00 ±0.01 and 6.00 ±0.02, Mg 9.60
±0.01 and 6.00 ±0.01, Zn 0.01 ±0.00 and 0.02 ±0.00, Fe
9.00 ±0.01 and 17.10 ±0.00, Cd undetectable, Ni
undetectable and Cu 0.30 ±0.00 and 0.16 ±0.00 PPM
respectively [80].
Fruits of Capsicum annuum contained
capsaicinoids, a family of compounds that give them the
characteristic pungent taste. The two major capsaicinoids,
capsaicin and dihydrocapsaicin, were responsible for up
to 90% of the total pungency of pepper fruits. Besides
capsaicin and dihydrocapsaicin, at least nine minor
capsaicinoids have been shown to occur in peppers [83-
89]. Capsaicin (C18H27NO3) is known with various
synonyms, i.e. N-[(4-Hydroxy-3- methoxybenzyl]-8-
methyl-trans-6-nonenamide, N-[(4- Hydroxy-3-methoxy-
phenyl)methyl]-8-methyl-trans-6- nonenamide, N-(3-
Methoxy-4-hydroxy benzyl)-8-methylnon- trans-6-
enamide, trans-8-methyl-N-vanillyl-6- nonenamide,
isodecenoic acid vanillylamide and 8- Methylnon-6-
enoyl-4-hydroxy-3-methoxy benzylamide. Capsaicin is a
decylenic acid amide of vanillyl-amine. On variation in
the acid portion of the molecule, different degree of
pungency of analogues has been observed [90-91].
Capsaicin is an odorless white crystal
(monoclinic, rectangular plates, scales in petroleum ether)
with severe burning pungency. One part in 100,000 can
be detected by tasting. It has a molecular weight of
305.4118 g/mol, melting point of 65°C, boiling point at
0.01 mm Hg is 210-220°C, sublimate at 115°C, UVmax
at 227, 281 nm (€ = 7000, 2500), slightly soluble in
carbon disulfide, hot water, practically insoluble in water,
freely soluble in alcohol, ether, benzene and chloroform.
It is fairly resistant to acids and alkali solutions at room
temperatures [92].
The capsaicin level of the fruits is lead in hot
taste of various type of capsicum sp. Capsaicin content
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was determined in twelve types of edible capsicum in
different areas in Indonesia. The result showed that green
paprika, yellow paprika, and red paprika contained no
capsaicin, while, capsaicin contents of chili tanjung, red
chili, red gendot, green gendot, green curly, japlak rawit,
red curly, red rawit and green rawit (cayenne) were 0.38;
0.83; 0.87; 0.88; 1.05; 1.09; 1.14; 1.85 and 2.11% (w/w),
respectively [93].
The polar, non polar and acid compounds of
intermediate polarity range from 33 to 34 compounds in
C. annuum. The number of lipid compounds from 32-33
and the total non-lipid compounds ranges from 88-103 in
C. annuum [94].
Chemical composition of n-hexane extracts from
Capsicum annuum at different stage of ripening (red,
green and small green) included: 2-Heptanal (E), 2-
Decenal (E) , ,4-Decadienal (E,E), cadienal, 2-Undecenal,
Tetradecane, Nonanoic acid, 9-oxo-, methyl ester,
Hexadecane, 2,6,10,14-tetramethyl, Pentadecane, Phenol,
2,6-bis(1,1-dimethylethyl)-4-methyl, Heptacosane,
Farnesol, Hexadecene, Tetradecanal, Heptadecane,
Myristic acid methyl ester, 9-Octadecene (E), 1-
Pentadecene, Undecane, exadecane, Oleic acid,
Octadecane, Oleic acid methyl ester, Pentadecanoic acid
methyl ester, Pentadecanoic acid, Neophytadiene, 2-
Pentadecanone, 6,10,14-trimethyl, 2-Decene,7-methyl-
(Z) Pentadecanoic acid, 14-methyl-, methyl ester
Palmitoleic acid methyl ester, Palmitic acid methyl ester,
Palmitic acid, Palmitic acid, 14-methyl- methyl ester,
Palmitic acid ethyl ester, Margaric acid methyl ester, 5-
Octadecene (E), 1-octadecadienoic acid methyl ester,
Linolenic acid methyl ester, Phytol, Stearic acid methyl
ester, Hexadecanamide, Eicosane, Octadecanal,
Nonadecanoic acid methyl ester, 1-Octadecene, Linoleic
acid, Docosane, Arachidic acid methyl ester, 9-
Octadecenamide (Z)- 1-Heneicosyl formate
,Octadecanamide, Heneicosanoic acid methyl ester,
Cyclodocosane ethyl, 4-Hexenoic acid, 3-methyl-2,6-
dioxo-, Cyclotetracosane, Behenic acid methyl ester,
Pelargonic acid vanillylamide, Palmitic acid 2-hydroxy-1-
hydroxymethyl) ethyl ester, Octadecane, Tricosanoic acid
methyl ester, Linoleic acid 2-hydroxy-1- hydroxymethyl)
ethyl ester, 2-Monolinolenin, Stearic acid, 2-hydroxy-1-
(hydroxymethyl) ethyl ester, Lignoceric acid methyl
ester, Cholest-5-en-3-ol (3b), Vitamin E ,Ergost-5-en-3-
ol, (3b,24R)-, Stigmast-5,22-dien-3-ol (3b,22E), Stigmast-
5-en-3-ol, (3b,24S), b-Amyrin, Viminalol and Stigmast-4-
en-3-one [95].
The phenolic constituents and ascorbic acid of
five pepper (Capsicum annuum L.) cultivars harvested in
the same season, geographic area and climatic conditions
was evaluated. It was found that Serrano pepper had the
highest ascorbic acid content, followed by Bell and
Caribe, whereas the lowest values were found in Jalapeno
and Anaheim. The highest contents of phenolic
compounds were in Caribe and Bell peppers. The total
flavonoid contents ranged from 25.38 ±3.44 (Anaheim) to
60.36 ±9.94 mg quercetin equivalents /100g fw (Caribe)
[96].
Four cultivars (Bronowicka Ostra, Cyklon,
Tornado, and Tajfun) of pepper fruit Capsicum annuum
L. were studied for phenolics contents. Nine compounds
were determined in the flavonoid and phenolic acid
fraction: trans-p-feruloyl-â-Dglucopyranoside, trans-p-
sinapoyl-â-D-glucopyranoside, quercetin 3-O-R-L-
rhamnopyranoside-7-O- â-D-glucopyranoside, trans-p-
ferulyl alcohol-4-O-[6-(2-methyl-3-hydroxypropionyl]
glucopyranoside, luteolin 6-C-â-D-glucopyranoside-8-C-
R-L-arabinopyranoside, apigenin 6-C-â-D-
glucopyranoside-8- C-R-L-arabinopyranoside, lutoeolin
7-O-[2-(â-D-apiofuranosyl)-â-D-glucopyranoside],
quercetin 3-OR- L-rhamnopyranoside, and luteolin 7-O-
[2-(â-D-apiofuranosyl)-4-(α-D-glucopyranosyl)-6-
malonyl]-α- D-glucopyranoside. The main compounds of
this fraction isolated from red pepper were sinapoyl and
feruloyl glycosides, and the main compound from green
pepper was quercetin-3-O-L-rhamnoside [97].
The flavonoid contents of C. annuum cultivated
in Thailand were determined in term of gallic acid (g) per
100 g of crude extract and per 100 g of dry herb powder.
The total phenolic content of capsicum sp. were in range
of 2.02-3.28 g/100 g of crude extract and 0.49-1.02 g/ 100
g of dry herb powder [98].
The total carotenoids (μg /g FW) and total
phenolic contents (μg GAE /g FW) of Pepper (Capsicum
annuum L. var frutescens): green 125.87±10.98 and
1012.02±12.56, yellow 611.54±09.45 and 1292.03±19.34
and red 1060.24±15.67 and 2150.25±24.37 respectively.
The total carotenoids (μg /g FW) and total phenolic
contents of Pepper (Capsicum annuum var.
glabriusculum): green 135.43±09.96 and 1206.25±15.34,
yellow 523.65±21.89 and 1919.45±24.27 and red
1148.08±10.56 and 3114.58±25.29 respectively. While,
the total carotenoids (μg /g FW) and total phenolic
contents of Capsicum annuum (Bell pepper): green
151.50±12.56 and 1205.54±16.43, yellow 859.54±20.87
and 2600.07±22.26 and red 1363.35±13.56 and
4135.45±33.33 respectively [99].
However Hernández-Ortega et al., found that
carotinoids of Capsicum annuum were:
guajillo 3406±4 μg/g, pasilla 2933±1 μg/g, and
ancho 1437±6 μg/g in dry weight basis [100].
The changes of vitamin C, vitamin E, β-carotene,
xanthophylls and phenolic compounds were investigated
in four pepper cultivars, two sweet: ‘King Artur’ and ‘Red
Knight’, and two hot: ‘Capel Hot’ and ‘Robustini’.
Additionally antioxidant activity of phenolic compounds
was evaluated by method with DPPH radical. It was
found that extracts obtained from hot fruits had a higher
vitamin E and β-carotene contents than from the sweet
ones. However, the extracts from sweet varieties were
characterized by higher antioxidant properties and
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phenolic compounds than the ones obtained from hot
peppers [101].
The leaves contained alkaloids, tannin and
flavonoids, the mean constituents of alkaloids, tannin and
flavonoids (mg/100g) in the leaves of three varieties of
Capsicum annuum varieties were 1.83, 5.82 and 3.86 in
Nsukka yellow; 1.76, 4.74 and 3.41 in Atarugu and
1.41, 5.75 and 3.77 in Otuocha respectively [4]. The
root contained steroid, alkaloid, coumarin, glycoside and
triterpenoid [33]. Ten sesquiterpenoids were isolated
from the ethyl acetate soluble fraction of a the methanolic
extract of the dried stems and roots of Capsicum annuum
[102].
Capsicum annuum contained appreciable
amount of L-asparaginase. The enzyme was purified from
the plant enzyme existed in two forms, only one having
antitumour activity. The purified enzyme has a molecular
weight of 120,000 ±500. The N-terminal and the C-
terminal amino acids are alanine and phenylalanine. The
enzyme has inseparable glutaminase activity and urease
activity [103].
Capsicum frutescens
Many bioactive compounds were isolated from
Capsicum frutescens including essential oils, alkaloids,
glycosides, phenolic compounds, flavonoids, ester,
terpenoids, noncarotenoids, lipoxygenase derivatives,
carbonyls, alcohols, hydrocarbons, hydroxybenzoic acid,
hydroxycinnamic acid, ascorbic acid, tannins, steroids,
capsaicin, dihydrocapsaicin, capsiconinoid, capsinoid,
Ortho- hydroxy- N- benzyl- 16- Methyl- 11, 14- diene-
octadecamide and 9, 12-diene-octadecanoic acid.
However, capsaicinoids (vanillylamides of monocarboxyl
acids) which were responsible for the pungency were
considered the most active compounds in the plant fruits
[55, 104-111].
The total phenolic compounds and the capsaicin,
dihydrocapsaicin, and chrysoeriol contents of C.
frutescens were analyzed. The capsaicin,
dihydrocapsaicin, and chrysoeriol contents were 9.2, 4.0,
and 2.1 mg/g extract, respectively. The total phenolic
content was 9.1 mg of gallic acid equivalent/g extract.
Capsaicin accounts for about 50% to 70% of the total
capsaicinoids [60]. However, Wetwitayaklung and
Phaechamud found that the total phenols in the crude
extract of C. frutescens Linn (Prick Hom Chiang Mai), C.
frutescens Linn (Prick Suan Tai) and C. frutescens Linn
(Prick Karen) (g/100g crude extract as Gallic acid) were
3.99, 3.49 and 3.20, while the total phenols in the dried
fruits of the same varieties (g/100g dried-fruit as Gallic
acid) were 0.83, 0.78 and 0.93 [98].
The total phenolic content and browning pigment
formation in bird chili (Capsicum frutescens Linn.) during
hot air drying at 70, 100 and 121°C was analyzed. It was
found that total phenolic content was decrease at the
beginning of the drying process, but it was increase when
the browning pigments were developed. Phenolic
compounds of fresh, red bird chili were less heat stable
than the ones of fresh, green bird chili [104].
The polar, non polar and acid compounds of
intermediate polarity range from 27 to 33 and the number
of lipid compounds varies from 24 to 29 in C. frutescens,
while, the total non-lipid compounds ranges from 84 to
96 in C. frutescens [94].
It was high in vitamin A and C, but low in
calories and sodium, potassium, magnesium and folic acid
[58]. The mineral composition of C. frutescens (Bird eye
chilli) and C. frutescens (Bird pepper) oils ranged Na
2.10 ±0.02 and 3.40 ±0.04, K 57.20 ±0.30 and 98.80
±0.15, Ca 30.00 ±0.03 and 32.00 ±0.03, Mg 18.00 ±0.10
and 13.20 ±0.10, Zn 0.10 ±0.01 and 0.04 ±0.00, Fe 17.10
±0.02 and 2.65 ±0.01, Cd 0.01 ±0.00 and undetectable,
Ni undetectable and 0.04 ±0.00 and Cu 0.26 ±0.01 and
1.05 ±0.00 PPM respectively [80].
PHARMACOLOGICAL EFFECTS
Capsaicin pharmacology
Pharmacokinetics of Capsaicin
In vitro studies in human skin, capsaicin
biotransformation was found to be slow and most
capsaicin remained unchanged while a small fraction was
metabolized. Three major metabolites identified for
capsaicin were 16-hydroxycapsaicin, 17-
hydroxycapsaicin and 16, 17- dihydrocapsaicin. It was
mainly eliminated by the kidneys with a small
untransformed proportion excreted in the feces and urine
[112-115].
Capsaicin is well absorbed from the topical
application on the skin, when 3% capsaicin solution
applied topically in 12 subjects in three different vehicles
(70% isopropyl alcohol; mineral oil; and propylene glycol
in 20% alcohol); it was rapidly and quickly absorbed and
reached maximum concentration. The half-life of
capsaicin was approximately 24 h [112].
Nearly 94% of orally administered capsaicin was
absorbed and maximum concentration in the blood was
reached 1 h after administration. A maximum distribution
of administered capsaicin in blood, liver, kidney and
intestine was seen in 1h and then diminished notably until
being undetected after 4 days [113].
Pharmacodynemics of Capsaicin
Capsaicin reacts to transient receptor potential
vanilloid 1 (TRPV1), previously known as the vanilloid
receptor, which is mainly expressed in the sensory
neurons. TRPV1 contained 838 amino acids and has a
molecular weight of 95 kDa in both humans and rats,
consisting of six transmembrane domains with a short
pore-forming region between the fifth and sixth
transmembrane domains. It was non-selective, ligand-
operated cationic channel located primarily in the small
fibers of nociceptive neurons. TRPV1 was also
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distributed in tissues of the brain, bladder, kidneys,
intestines, liver, polymorphonuclear granulocytes, mast
cells, keratinocytes, glial cells, and macrophages. It
couples with a non-specific cation channel permeable to
sodium and calcium ions, and is located in the plasma
membrane and the endoplasmic reticulum where regulates
intracellular calcium levels. Binding of capsaicin with
TRPV1 increases intracellular calcium, triggering release
of substance P and the calcium gene-related peptide
(CGRP). Contact between capsaicin and sensory neurons
produces pain, inflammation and a localized heat
sensation. When applied locally to skin, it promotes an
analgesic response due to desensitizing of the sensory
neurons caused by substance P depletion [116-121]
. effects against ethanol- and indomethacine-associated
Pharmacological effects of Capsaicin
Capsaicin and its analogues were used topically
to treat chronic pain syndromes musculoskeletal pain,
osteoarthritis, rheumatoid arthritis, post-herpetic neuralgia
and diabetic neuropathy [122-123]. Topical application of
capsaicin evokes burning pain, neurogenic inflammation
(vasodilatation and plasma extravasation), and
hyperalgesia to heat and mechanical stimuli [124-126].
The treated area becomes less sensitive to pain, after
repeated applications, this effect made capsaicin a
peripherally acting analgesic in chronic painful complains
[127-128]. The sensory dysfunction after capsaicin
application to the skin resulted from rapid degeneration of
intracutaneous nerve fibers. The effect of intradermal
injection of capsaicin on morphological changes in
cutaneous nerve fibers that would account for its
analgesic properties was studied by comparing cutaneous
innervation in capsaicin-treated skin with psychophysical
measures of sensation. At various times after capsaicin
injection, nerve fibers were visualized
immunohistochemically in skin biopsies and were
quantified. In normal skin the epidermis is heavily
innervated by nerve fibers immunoreactive for protein
gene product (PGP) 9.5, whereas fibers immunoreactive
for substance P (SP) and calcitonin gene-related peptide
(CGRP) are typically associated with blood vessels. There
was nearly complete degeneration of epidermal nerve
fibers and the subepidermal neural plexus in capsaicin-
treated skin, as indicated by the loss of immunoreactivity
for PGP 9.5 and CGRP. The effect of capsaicin on dermal
nerve fibers immunoreactive for SP was less obvious.
Capsaicin decreased sensitivity to pain produced by sharp
mechanical stimuli and nearly eliminated heat-evoked
pain within the injected area. Limited reinnervation of the
epidermis and partial return of sensation occurred 3 weeks
after treatment; reinnervation of the epidermis was; 25%
of normal, and sensation improved to 50–75% of normal
[128].
Anticancer activity of capsaicin was recorded in
different types of cancer, capsaicin blocked breast cancer
cell migration and killed prostate cancer cells.
Dihydrocapsaicin induced autophagy in HCT116 human
colon cancer cells. Capsaicin also inhibited the growth of
leukemic cells. Investigation of the mode of action of
capsaicin showed that it induced cell cycle arrest,
apoptosis, and inhibited cellular metabolism. Capsaicin
selectively inhibited the growth and induced apoptosis of
immortalized or malignant cell lines, but not of normal
cell lines. However, the metabolites of capsaicin (such as
the reactive phenoxy radicals) may attack the DNA and
trigger the mutagenicity and malignant transformation
[129-137].
Capsaicin protected the gastric mucous against
ulceration by ethanol when used at low concentrations
(0.13–160 μM) in rats. Capsaicin exerted protective
gastropathy in 84 healthy human subjects, with a dose
dependent decrease in base gastric acid output (ED 50 for
400 μg capsaicin) and increased gastric emptying [138-
139]. Gastrointestinal system also contained capsaicin-
sensitive sensory nerves which plays a crucial role in
maintenance of gastrointestinal mucosa integrity against
injurious interventions. A low dose of capsaicinoids could
increase the basal gastric mucosal blood flow and gastric
mucus secretion, and facilitate gastric epithelial
restitution, which were beneficial to gastrointestinal
defense [140].
Capsaicin exhibited a hypoglycaemic effect in
dogs; insulin release was increased [55]. When capsaicin
injected intravenously or into the carotid sinus, it caused
apnoea decreased heart rate and produced hypotension
[91]. Cardiovascular system contains capsaicin-sensitive
sensory nerves, which participated in regulation of
cardiovascular function through activation of TRPV and
Substance P and the release of CGRP. Many studies
showed that capsaicinoids had beneficial effects on the
cardiovascular system to treat ischemic heart disease,
hypertension and atherosclerosis [141-143].
Capsaicin also inhibited platelet aggregation and
the activity of clotting factors VIII and IX, a property
which reduce the incidence of cardiovascular diseases
[144-145].
Capsaicin, when fed along with cholesterol-
containing diets to female albino rats, it prevented
significantly the rise of liver cholesterol levels [55].
Capsaicin is used on vegetation such as crops
and trees, buildings, and garbage containers. It is
registered to repel vertebrate pests such as rabbits,
squirrels, deer, voles, raccoons, cats, dogs, and skunks. It
is applied to foliage of plants to deter feeding by insects
such as spider mites, lace bugs, and other invertebrates.
Capsaicin is used as an insecticide in addition to its use as
a repellent [146-147].
Capsaicin and dihydrocapsaicin exerted
antimicrobial effects against Bacillus cereus, Bacillus
subtilis, Clostridium sporogenes, Clostridium tetani, and
Streptococcus pyogenes [148].
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Other Pharmacological effects of C. annuum and C.
frutescens
Antimicrobial effects
Capsicum annuum
The butanol extract of Capsicum annuum fruit
showed high antimicrobial activity against all the tested
pathogens while other extracts showed comparatively
moderate activity. The ethanol extract (100 mg/ml) of
Capsicum annuum showed high antimicrobial activity
against Micrococcus sp (20 mm), Bacillus (10 mm), E.
Coli (17 mm), Pseudomonas sp (16mm) and Citrobacter
sp(15 mm). The chloroform extract of Capsicum annuum
showed less antimicrobial activity against all the tested
pathogens [149]. The inhibitory effect of the extract of
Capsicum annuum bell pepper type was evaluated against
Salmonella typhimurium and Pseudomonas aeruginosa,
inoculated in minced beef meat mixed with different
concentrations of the extract, and stored at 7 degrees °C
for 7 days. The minimum inhibitory concentration of the
extract to prevent the growth of S. typhimurium in minced
beef was 1.5 ml/100 g of meat. In the case of P.
aeruginosa, a concentration of 0.3 ml of the extract/100 g
of meat showed a bacteriostatic effect, while a
concentration of 3 ml/100 g of meat showed a bactericidal
effect [150].
Antibacterial activity of Capsicum annuum was
evaluated against pathogenic strains isolated from the
urinary tract (2 Klebsiella pneumoniae, 2 Pseudomonas
aeruginosa and 2 E.coli). The different concentrations of
the plant extracts showed antibacterial activity at 5 and
10mg/ml against the tested microorganisms [151].
Capsicum frutescens
C. frutescens exerted antibacterial and
antifungal properties. CAY-1, a novel saponin isolated
from C. frutescens, was found to be active against 16
different fungal strains, it acted by disrupting the
membrane integrity of fungal cells [152]. The ethanol
extract (100 mg/ml) of Capsicum frutescens showed high
antimicrobial activity against Micrococcus sp (17 mm),
Bacillus (10 mm), E. Coli (14 mm), Pseudomonas sp (12
mm) and Citrobacter sp (13 mm). The chloroform extract
of Capsicum frutescens showed less antimicrobial activity
against all the tested pathogens [149].
The minimal inhibitory concentration of C.
frutescens was determined against six strains of Gram
positive (Staphylococcus aureus UFPEDA02,
Enterococcus faecalis ATCC6057, Bacillus subtilis
UFPEDA 86), and Gram negative (Escherichia coli
ATCC25922, Klebsiella pneumonia ATCC29665,
Pseudomonas aeruginosa UFPEDA416) bacteria and one
yeast strain (Candida albicans UFPEDA 1007), but for all
of these microorganisms, the necessary concentrations
were higher than 1000 μg/ml [106].
The antifungal potential of aqueous leaf and fruit
extracts of Capsicum frutescens against four major fungal
strains associated with groundnut storage (Aspergillus
flavus, A. niger, Penicillium sp. and Rhizopus sp) was
studied. The minimum inhibitory concentrations (MIC)
and minimum fungicidal concentration (MFC) of C.
frutescens extracts were determined. MIC values of the
fruit extract were lower compared to the leaf extract. At
MIC, leaf extract showed strong activity against A. flavus
(88.06%), while fruit extract against A. niger (88.33%) in
the well diffusion method. Groundnut seeds treated with
C. frutescens fruit extract (10mg/ml) showed a higher rate
of fungal inhibition [153].
Insecticidal and anthelmintic effects
The insecticidal activities of red pepper
(Capsicum annuum L.) fruit powder were investigated
against Rhyzopertha dominica and Sitophilus granaries.
This powder was mixed with 20g wheat grains as direct
admixtures at different rates viz, 0, 0.5, 0.85, 1.5, 3 and
5% (w/w) to assess for mortality and reduction of Fl
progeny. The results revealed that red pepper in low
concentrations did not cause complete mortality on two
insects after 14 days. It caused complete reduction in Fl
progeny of S. granarius and R. dominica at highest tested
dosages [154].
Capsicum annuum and Capsicum frutescens fruit
and seed powders were evaluated in the laboratory for the
control of Callosobruchus maculatus (F.) in stored
cowpea and Sitophilus zeamais in stored maize.
Capsicum frutescens seed powder and Capsicum annuum
seed powder dust were toxic to C. maculatus and S .
zeamais at the rate of 5.0g, 7.5g per 50g cowpea and 50g
maize within 48hrs and 96hrs respectively [155].
Capsicum frutescens L. (fruit and seed) and C.
annuum Miller (fruit and seed) were examined as
fumigant insecticides on cowpea bruchid. The powders
were applied at rates 0.0 (control), 2g and 3.0g/20g of
cowpea seeds either directly for contact with the insect
pest or in plastic containers to assess fumigant toxicity of
their volatiles. Results of contact toxicity assay showed
that powders of C. frutescens and C. annum seeds were
highly effective against the adult C. maculatus evoking
100% mortality within 2 days of application at 3g/20g of
cowpea seeds. There was no progeny development of the
bruchid in samples treated with capsicum species. The
survival of the bruchid from eggs to adults when treated
with the plant powders showed that there was
significantly (P<0.05) more % progeny development in
the control (69.32%) compared to others [156].
The mosquito repellent effect of extracts of
Capsicum frutescens was studied against A. aegypti
mosquitoes. The plant parts were dried in the shade and
ground to powder. The volatile constituents of the
powders were isolated by dry distillation, and the
distillates used in repellency tests on A. aegypti
mosquitoes. The distillates of the fruits of C. frutescens
were effective for 2.5 hours. The mixture of C. frutescens
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and C. papaya was effective for 4 hours, whilst that of C.
frutescens and C. dactylon was effective for 3 hours. The
mixture of all three extracts was effective for 4 hours, i.e.
giving the same duration of protection as the mixture of
C. frutescens and C. papaya. Mixtures of highly repellent
extracts are likely to give high repelling products although
the repellency of the mixture is not likely to be a simple
additive product of the repellencies of the constituent
extracts [157].
The insecticidal activity of different
concentrations of methanol extract of fruits and leaves of
C. frutescens was investigated against 2nd and 3rd instar
larvae of A. aegypti. The mortality of the larvae was
found to be concentration dependent. Among larvae, 2nd
instar larvae were shown to be more sensitive than 3 rd
instar larvae. The fruit extract has shown more killing
effect than leaf extract [105].
The antiparasitic effect of the aqueous extract of
Capsicum frutescens against the fish ectoparasite
Ichthyophthirius multifiliis, was evaluated under in vitro
and in vivo conditions. The results in the in vitro
conditions showed that the aqueous extracts of C.
frutescens with the ratios (VSS/VT, VSS: the volume of
stock solution; VT: the volume of total solution) of 1:32
and 1:64 led to more than 70 % mortality of I. multifiliis
theronts during 4h of exposure and significantly reduced
the survival of the tomonts and the total number of
theronts released by the tomonts within 22h (P<0.05). A
96-h bioassay was carried out to determine the acute
toxicity of the aqueous extract of C. frutescens to
goldfish. No visible effect was observed in the treatments
with the aqueous extracts of C. frutescens with the ratios
(VSS/VT) of 1:32, 1:64 and 1:128, while in the other
treatments, the erratic behaviour of fish was noted. In
addition, in vitro tests demonstrated that the aqueous
extract of C. frutescens had an adverse effect on I.
multifiliis trophonts in situ. Fish treated with the aqueous
extracts of C. frutescens in ratios VSS/VT of 1:32 and
1:64 carried significantly fewer parasites than the control
and the other treatments (P<0.05) [158].
Antioxidant effect
Capsicum annuum
Antioxidant compounds and their antioxidant
activity in 4 different colored (green, yellow, orange, and
red) sweet bell peppers (Capsicum annuum L.) were
investigated. The free radical scavenging abilities of
peppers determined by the 2, 2~-diphenyl-1-
picrylhydrazyl (DPPH) method. Antioxidants present in
the (Capsicum annuum L.) appeared beneficial and can
protect the food or body from oxidative damage induced
by free radicals and reactive oxygen [72].
Four cultivars (Bronowicka Ostra, Cyklon,
Tornado, and Tajfun) of pepper fruit Capsicum annuum
L. were studied for antioxidant activity. Capsaicin and
dihydrocapsaicin were the main antioxidant components.
A high correlation was found between the content of these
compounds and the antioxidant activity. Their antioxidant
activities were elucidated by heat-induced oxidation in the
α-carotene-linoleic acid system and the antiradical
activity by the 1,1-diphenyl-2-picrylhydrazyl (DPPH)
decoloration test. The highest antioxidant activity in the α
-carotene-linoleic acid system was found for trans-
psinapoyl- α -D-glucopyranoside, which was lower than
the activity of free sinapic acid. Quercetin 3-OR- L-
rhamnopyranoside had the highest antiradical activity in
the DPPH system, which was comparable to the activity
of quercetin. The activities of capsaicin and
dihydrocapsaicin were similar to that of trans-p-feruloyl-
α -D-glucopyranoside in the DPPH model system [97].
The antioxidant activity of five pepper
(Capsicum annuum L.) cultivars harvested in the same
season, geographic area and climatic conditions were
evaluated by DPPH and ABTS. The Bell and Caribe
extracts showed the highest (p<0.05) stabilization of
ABTS. The highest oxidation inhibition percentage for
radical DPPH was observed in Caribe extract, coinciding
with the highest levels of gallic acid, chlorogenic acid,
epicatechin, rutin, luteolin, resveratrol (r ≥0.85) and
ascorbic acid [96].
Consumption of Capsicum annuum for 4 weeks
has been found to increase the resistance of serum
lipoproteins to oxidation in adult men and women, the
antioxidant property of capsaicinoids gave further benefit
in the treatment of cardiovascular diseases [159].
Red pepper or an equivalent amount of
capsaicin, when fed along with cholesterol-containing
diets to female albino rats, they prevented significantly
the rise of liver cholesterol levels [55].
Carotenoids extracted from dried Capsicum
annuum were evaluated for their antioxidant activities.
Guajillo pepper carotenoid extracts exhibited good
antioxidant activity and had the best scavenging capacity
for the DPPH+ cation (24.2%) [100].
Capsicum frutescens
The antioxidant activities (IC50) of C. frutescens
Linn (Prick Hom Chiang Mai), C. frutescens Linn (Prick
Suan Tai) and C. frutescens Linn (Prick Karen) were
1317.85, 2436.37 and 4232.98 μg respectively [52]. The
ethanolic extract of C. frutescens had effective 2,2-
diphenyl-1-picrylhydrazyl (DPPH) ABTS and 2,2'-azino-
bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)
ABTS+ scavenging activities (EC50 values of 302.3 and
82.6 g/ml, respectively), and the percentage of antioxidant
activity determined using the β-carotene-linoleic acid
assay ranged from 15 to 47% [60]. The antioxidant
capacity of bird chili (Capsicum frutescens Linn.) during
hot air drying at 70, 100 and 121°C was analyzed by three
different methods (ferric-reducing antioxidant power
(FRAP) assay; radical cation decolorization assay; and
DPPH, free radical scavenging activity). The antioxidant
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capacity of dried bird chili was dependent on the degree
of browning and the drying temperature. All the
antioxidant capacities of the dried products were higher
than for the fresh ones, except after drying at 70°C [104].
Cytotoxic effects
Four types of chili (Capsicum annuum) extracts,
categorized according to color (green and red), and size
(small and large) were studied in Hep-G2 cells. Red small
(RS) chili had an LC50 value of 0.378 ± 0.029 mg/ml
compared to green big (GB) 1.034 ± 0.061 mg/ml and
green small (GS) 1.070 ± 0.21 mg/ml. Red big (RB) was
not cytotoxic. Capsaicin content was highest in RS and
produced a greater percentage of sub-G1 cells
(6.47 ± 1.8%) after 24 h exposure compared to GS
(2.96 ± 1.3%) and control (1.29 ± 0.8%). G2/M phase was
reduced by GS compared to RS and control cells. RS at
the LC50 concentration contained 1.6 times the amount of
pure capsaicin LC50 to achieve the same effect of
capsaicin alone. GS and GB capsaicin content at the LC50
value was lower (0.2 and 0.66, respectively) compared to
the amount of capsaicin to achieve a similar reduction in
cell growth [160].
Capsicum annuum L. var. angulosum Mill.
extracts showed relatively higher cytotoxic activity
against two human oral tumor cell lines (HSC-2, HSG)
than against normal human gingival fibroblasts (HGF),
suggesting a tumor-specific cytotoxic activity [161].
The extracts of Indian spices like chili pepper,
cloves, black pepper and black cumin were investigated
for cytotoxic effect. In studying the in vitro anticancer
activities of aqueous and ethanolic extracts against the
TE-13 (esophageal squamous cell carcinoma) cell line,
DAPI staining and DNA fragmentation assays showed
maximum cell death and apoptotic cell demise (88%) to
occur within 24 hours with an aqueous extract of chili
pepper at 300 μl/ml [162].
By using an in vitro brine shrimp lethality bio-
assay, the LC50 of Capsicum frutescens was 83.33 μg/ml
[163].
Immuno-modulatory effect
The immunological effects of red pepper
(Capsicum annuum Lin.) extracts (capsicum extract) and
its main pungent capsaicin was investigated on T helper 1
(Th1) and 2 (Th2) cytokine production in cultured murine
Peyer's patch (PP) cells in vitro and ex vivo. Direct
administration of capsicum extract (1 and 10 mug/ml) and
capsaicin (3 and 30 muM) resulted in suppression of
interleukin (IL)-2, interferon (IFN)-gamma, IL-4 and IL-5
production. In an ex vivo experiment using PP cells
removed from the mice after oral administration
of capsicum extract (10 mg/kg/day for 4 consecutive
days), IL-2, IFN-gamma and IL-5 increased in response to
concanavalin A (Con A). Oral administration of 3
mg/kg/day capsaicin, also enhanced IL-2, INF-gamma
and IL-4 production in response to Con A stimulation but
did not influence the production of IL-5. Orally
administered capsazepine (3 mg/kg/day), a selective
transient receptor potential vanilloid 1 (TRPV1)
antagonist, slightly enhanced IL-2 production also
irrespective of Con A stimulation. The capsaicin-induced
enhancement of both IL-2 and IFN-gamma production
was not reduced by oral administration of capsazepine (3
mg/kg/day), suggesting a TRPV1 receptor-independent
mechanism. Flow cytometric analysis revealed that the
population of CD3(+) cells in the PP cells was
significantly reduced while CD19(+) cells increased after
oral administration of capsicum extract (1 and 10
mg/kg/day) and capsaicin (0.3 and 3 mg/kg/day).
Capsazepine (3 mg/kg/day) weakly but significantly
reversed these effects. Orally
administered capsicum extract and capsaicin did not
change the T cell subset (CD4(+) and CD8(+), Th1 (IFN-
gamma(+) and T2 (IL-4(+) ratio [164].
It appeared that dendritic cells, a key cell type in
immune responses, have the receptor for capsaicin, and
engagement of this receptor has powerful immune
consequences. The intratumoral administration of
capsaicin into a preexisting tumor results in retarded
progression of the injected tumor regardless of whether
the tumor is at its early or late stage. Furthermore, it leads
to significant inhibition of growth of other, uninjected
tumors in the same animal. Capsaicin-elicited immunity is
shown to be T cell-mediated and tumor-specific [165].
Vanilloid receptor 1 (VR1) is expressed
on immune cells. VR1 can regulate immunological
events in the gut in response to its ligand Capsaicin (CP).
Oral administration of CP attenuates the proliferation and
activation of autoreactive T cells in pancreatic lymph
nodes (PLNs) but not other lymph nodes. Engagement of
VR1 enhances a discreet population of
CD11b(+)/F4/80(+) macrophages in PLN, which express
anti-inflammatory factors interleukin (IL)-10 and PD-L1.
This population is essential for CP-mediated attenuation
of T-cell proliferation in an IL-10-dependent manner
[166].
The effect of a methanolic C. annuum L. extract
(CAE) was investigated in mice model of ovalbumin-
induced allergic airway inflammation. Animals were
treated with CAE by oral gavage before ovalbumin
challenge. Oral treatment with CAE significantly reduced
the pathophysiological signs of allergic airway disease,
including increased inflammatory cell recruitment to the
airways, airway hyper-responsiveness, and increased
levels of T-helper type 2 cytokines. Reactive oxygen
species were also decreased in cells from broncho-
alveolar lavage fluid. In addition, the administration of
CAE attenuated ovalbumin-induced increases in NF-κB
activity in lungs [167].
Treatment with capsicum oleoresin of lactating
dairy cows increased the relative proportion of
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lymphocytes compared with the control. It also increased
the proportion of total CD4(+) cells and total CD4(+)
cells that co-expressed the activation status signal and
CD25 in blood. The percentage of peripheral blood
mononuclear cells (PBMC) that proliferated in response
to concanavalin A and viability of PBMC were not
affected by treatment. Cytokine production by PBMC was
not different between control and capsicum oleoresin
treated cows. Expression of mRNA in liver for key
enzymes in gluconeogenesis, fatty acid oxidation, and
response to reactive oxygen species were not affected by
treatment. No difference was observed due to treatment in
the oxygen radical absorbance capacity of blood plasma
[168].
The effects of 10 mg/kg Capsicum oleoresinon
on growth performance and immune responses was
studied in weaned pigs experimentally infected with
porcine reproductive and respiratory syndrome virus
(PRRSV). The results indicate that supplementation
with capsicum oleoresin reduces the adverse effects of
PRRSV by improving the immune responses of pigs
[169].
Hot water-soluble crude polysaccharide (HCAP-
0) that was obtained from the fruits of Capsicum annuum
showed potent anti-complementary activity. The activity
was unchanged by pronase digestion, but decreased by
periodate oxidation. The HCAP-0 was fractionated by
DEAE ion-exchange chromatography to give two major
fractions, HCAP-II and III. These two fractions were
finally purified by gel filtration to give HCAP-IIa,
HCAPIIIa1, and IIIa2 fractions that had high
anticomplementary activities. The HCAP-IIIa1 and IIIa2
consisted of homogeneous polysaccharides. The
anticomplementary activities were unaffected by
treatment with polymyxin B, indicating that the modes of
complement activation were not due to preexisting
lipopolysaccharide [170].
Anti-inflammatory effect
Topical preparations of capsaicinoids are widely used
for musculoskeletal disorders as a complementary
therapy. The potential effects of both topical
capsaicinoids-containing patch and local subcutaneous
capsaicin application on the anti-inflammatory action of
NSAID were examined. Carrageenan-induced paw
oedema of rats was used as the inflammation model.
Topical capsaicinoids-containing patch application or
local capsaicin injection (2, 10, 20 μg/paw) alone did not
cause any effect on oedema volume and weight. However,
the combination of diclofenac with topical capsaicinoids-
containing patch significantly increased the effectiveness
of diclofenac on inflammation. Evans blue content of the
paws that represents plasma extravasation was decreased
by capsaicinoids-containing patch with and without
diclofenac [171].
The anti-inflammatory activity of Capsicum
annuum was assessed by inhibiting Soyal lipoxygenase
(LOX) enzyme. The results showed higher % of LOX
inhibition by green capsicum (46.12 %) followed by
yellow (44.09 %) and red capsicum (32.18 %) [172].
Carotenoids extracted from dried Capsicum
annuum were evaluated for their analgesic activities.
Carotenoids extracts exhibited significant peripheral
analgesic activity at 5, 20, and 80 mg/kg and induced
central analgesia at 80 mg/kg. The guajillo pepper
carotenoids extract was also exerted anti-inflammatory
activity, they significantly inhibited oedema formation
and progression at a dose of 5 mg/kg compared to the
control treatment at 1, 3, and 5 hours after carrageenan
injection (p<0.05). A similar response was obtained with
indomethacin compared to the control treatment.
Interestingly, at higher doses (20 and 80 mg/kg), the
guajillo pepper extract significantly reduced oedema
generated by the carrageenan at the 5 h time point
(p<0.05) [100].
The anti-inflammatory effects of ethyl acetate
extract of Capsicum frutescens (CFE) was examined on
rat hind paw inflammation induced by subplantar
injections of fresh egg albumin (0.5 ml/kg). Ethyl acetate
extract of Capsicum frutescens produced anti-
inflammatory effects that were comparable to diclofenac
[173].
Cardiovascular effects
In anesthetized dogs iv injections of capsaicin
(10-300 µg/kg) caused a transient rise in mean systemic
blood pressure followed by a sustained fall, whereas in
anesthetized rabbits capsaicin caused only hypotension.
The induced hypertension in dogs was not influenced by
treatment with hexamethonium, tolazoline and
phentolamine. The hypotension in dogs and rabbits was
diminished by atropine. In atropine-treated dogs the heart
rate was not influenced or was increased slightly by
capsaicin in spite of a marked rise in blood pressure.
Capsaicin (2 x 10-8 to 2 x 10-6 g/ml) did not influence the
rate or the contractile force of isolated dog and rabbit
atria. Capsaicin caused a sustained increase in the tension
of strips of proximal and distal mesenteric arteries and
proximal and distal renal arteries of the dog. The tension
increment was not significantly altered by phentolamine.
The contractile effect of capsaicin in dog superior
mesenteric arteries was slightly reduced by decreasing
[Ca++] to 0.73 mM (1/3 normal [Ca++]) and was abolished
by removal of Ca++ from the bathing media. Strips of dog
coronary artery showed contracture in response to
capsaicin. Cerebral arterial strips also contracted after
capsaicin administration. On the other hand, strips of dog
aorta and main pulmonary artery did not respond to
capsaicin. Capsaicin did not increase the tension of strips
of rabbit aorta, main pulmonary artery and superior
mesenteric artery. The contractile response of rabbit
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ascending aorta to transmural electrical stimulation at 5
and 20/sec was potentiated and prolonged by 2 X 10 -6 and
10-5 g/ml capsaicin. These findings suggest (1) that the
depressor response of dogs and rabbits to capsaicin is
associated with cholinergic mechanisms, (2) that
capsaicin causes hypertension in dogs by its action on
peripheral vasculatures but not on the heart and (3) that
capsaicin-induced vasoconstriction is related intimately to
extracellular Ca++ but not to an adrenergic mechanism
[174].
Capsicum annuum contained an anticoagulant
that helps prevent the blood clots that can cause heart
attacks [72].
Natural α-amylase and α-glucosidase inhibitors
from food-grade plants offer an attractive strategy to
control postprandial hyperglycemia for type 2 diabetes
management. Concurrently associated macrovascular
complication of hypertension can be managed by similar
extracts by inhibition of angiotensin I-converting enzyme
(ACE). Nine types of pepper (Capsicum annuum) were
investigated for inhibitory activity against α-amylase and
α-glucosidase and angiotensin I-converting enzyme
(ACE) inhibitors. Several pepper extracts had high α-
glucosidase inhibitory activity, which was not correlated
to total phenolic content and free radical scavenging-
linked antioxidant activity. Select extracts such as Green
pepper and Long hot pepper had less or no inhibitory
effect on the α-amylase activity. Among various water
extracts of Red pepper had the highest ACE inhibitory
activity [175].
An in-vitro thrombolytic model was used to
check the clot lysis effect of Capsicum frutescens. A
combination of honey and Capsicum frutescens was also
investigated along with streptokinase as a positive control
and water as a negative control. By using an in vitro
thrombolytic model Capsicum frutescens and a
combination of honey and Capsicum frutescens showed
57.40% and 44.54% clot lysis effect respectively (163).
Anti-obesity effect
The anti-obesity effects of water extracts of
seven Capsicum annuum L. varieties, Putgochu (Pca),
Oyee gochu (Oca), Kwari putgochu (Kca), Green pepper
(Gca), Yellow paprika (Yca), Red paprika (Rca) and
Cheongyang gochu (Cca), were examined through the
evaluation of lipoprotein lipase (LPL) mRNA expression
level in 3T3-L1 cells (mouse pre-adipocytes). After
capsaicin elimination by chloroform defatting, freeze-
dried powder of Cca was treated to 3T3-L1 cells and anti-
obesity effects were examined by determining the LPL
mRNA level using the RT-PCR method. Of the primary
fractions, only proven fractions underwent secondary and
tertiary re-fractionating to determine anti-obesity effects.
From seven different Capsicum annuum, there was a
significant decrease of the LPL mRNA expression level
of 50.9% in Cca treatment compared to the control group.
A significant decrease of the LPL mRNA expression level
was shown in primary fractions (Fr) 5 (36.2% decrease)
and 6 (30.5% decrease) of the Cca water extracts. Due to
the impurities checked by UPLC chromatography, Fr 5
and 6 were re-fractionated to determine the LPL mRNA
expression level. Treatment of Fr 6-6 (35.8% decrease)
and Fr 5-6 (35.3% decrease) showed a significant
decrease in the LPL mRNA expression level. When
analyzed using UPLC, major compounds of Fr 6-6 and Fr
5-6 were very similar. Subsequently, Fr 6-6 and Fr 5-6
were re-fractionated to isolate the major peak for structure
elucidation. Treatment of Fr 5-6-1 (26.6% decrease) and
Fr 6-6-1 (29.7% decrease) showed a significant decrease
in the LPL mRNA expression level [176].
Other effects
The effect of aqueous extracts of Capsicum
frutescens on the healing acute gastric ulcer induced by
aspirin was investigated in rats ( at doses of 300 and 600
mg/kg bw for seven days). The results revealed that oral
administration of the aqueous extract at a dose of
600mg/kg bw, reduced the length of gastric ulcer, volume
of gastric juice, and improved histopathological changes
[177].
Capsaicin produces a protective effect in rat lung
and liver by strengthening the pulmonary antioxidant
enzyme defense system. Capsaicin treatment caused
desensitization of the respiratory tract mucosa to a variety
of lung irritants. C. frutescens also increased urine
output in a dose of 10 ml/kg [178].
Adverse effects and toxicity
Internally, it may cause gastrointestinal
cramping, pain, and diarrhoea. Topically, it may cause
painful irritation of mucous membrane [179].
Oral LD50 values for capsaicin are 161.2 mg/kg
(rats) and 118.8 mg/kg (mice), with haemorrhage of the
gastric fundus observed in some of the animals that died.
However, capsaicin is considered to be safe and effective
as an external analgesic counterirritant. Rabbits fed with
C. annuum powder at 5 mg/kg per day in the diet daily for
12 months showed damaged liver and spleen. A rabbit
skin irritation test of C. annuum fruit extract at 0.1% to
1.0% produced no irritation but caused neoplastic changes
in the liver and intestinal tumours were observed in rats
fed red chili powder at 80 mg/kg per day for 30 days.
High doses administered over extended period of time can
cause chronic gastritis, kidney damage, liver damage and
neurotoxic effects [180-181]. Saito and Yamamoto found
that the acute oral LD50 values of Capsaicin were
determined to be 97.4 mg/kg and 118.8 mg/kg in female
and male mice, respectively, and 148.1 mg/kg and 161.2
mg/kg in female and male rats, respectively. Mice and
rats dosed orally with 96 to 200 mg/kg capsaicin
demonstrated immediate salivation, convulsions,
reddening of the skin, and dyspnea, or labored breathing.
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Animals either died within 26 minutes of dosing, or
showed no further symptoms 24 hours after dosing [182].
Inhalational exposure to capsaicinoids in pepper
sprays damaged rat bronchial, tracheal, nasal, alveolar
cells and causing acute inflammations [183].
Acute myocardial infarction was recorded in 40
years old man admitted to emergency department with
complains of chest pain and dyspnea after exposure the
pepper gas that sprayed to environment during a social
event [184].
Capsicum annuum should not be used during
pregnancy and lactation, in people with hypersensitivity
and in children. The plant should not be used on open
wounds or abrasions, or near the eyes [185]. Interactions
were reported with concomitant administration of
Capsicum annuum with aspirin and salicylic compounds.
It also decreased the actions of α-adrenergic blockers,
clonidine and methyldopa [180,185-186].
Dose
Capsicum annuum
30-60 mg of powder of fruits [55].
Liquid extract is prepared by percolating 100 gm
of the plant extract with 60 mg of ethanol, to be used as
an antirheumatic. External daily dose of semi solid
preparations containing maximum of 50 mg of capsaicin
in 100 gm neutral base is also used as an antirheumatic
and applied to the affected area not more than 3 or 4 times
daily [180].
Capsicum frutescens
1/10 to 2 drops, very largely diluted. Tinctura
Capsici :1/10 to 10 minims. Emplastrum Capsici. Plaster
(Composed of Oleoresin of Capsicum and Rubber Plaster)
as rubefacient [187].
CONCLUSION
The paper reviewed Capsicum annuum and
Capsicum frutescens as promising medicinal plants with
wide pharmacological activities which could be utilized in
several medical applications as a result of their
effectiveness and safety.

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