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C H A P T E R

9
Antioxidant Spices and Herbs Used in Diabetes
Roberta Cazzola, Benvenuto Cestaro
Department of Biomedical and Clinical Sciences ‘L. Sacco’, University of Milan, Milan, Italy

List of Abbreviations
Diet has been recognized as a cornerstone in the man-
ACSOs  S-alk(en)yl-l-cysteine sulfoxides agement of diabetes mellitus. Before the introduction of
AGEs  Advanced glycation end-products
the therapeutic use of insulin, diet was the main form of
MCSO  S-methyl-l-cysteine sulfoxide
1-PeCSO  S-1-propenyl-l-cysteine sulfoxide treatment of the disease, and dietary measures included
2-PeCSO  S-2-Propenyl-l-cysteine sulfoxide the use of culinary herbs and spices. From the termino-
SGLT-1 Na+/glucose cotransporter-1 logical point of view, culinary herbs are considered to
be the leaves of a plant used to flavor foods, and spices
are any other part of the plant used in cooking, often
INTRODUCTION in the dry state. Generally, while spices have an aro-
matic and pungent taste which restricts their use, culi-
Diabetes mellitus is a metabolic disorder character- nary herbs have a more delicate and pleasant taste that
ized by chronic hyperglycemia associated with complete makes it possible to use them in larger quantities and in
or partial deficiencies in insulin secretion or function a greater number of food preparations. For thousands of
and is one of the most common chronic diseases affect- years, spices and herbs have been used not only to flavor
ing millions of people globally [1]. Type 1 diabetes is and preserve foods, but also as medicaments. In ancient
an autoimmune disease caused by the destruction of civilizations, the choice of herbs or spices to be used for
pancreatic beta cells, and characterized by a deficiency therapeutic purposes depended on their local availabil-
in the secretion of insulin, while type 2 diabetes is due ity; for example, in ancient Greece and Rome the herbs
to abnormal secretion and/or action of insulin, or both. were more commonly used, while spices were prevalent
Hyperglycemia and insulin resistance promote an oxi- in the Middle East, North Africa, and India. In Europe,
dative stress and a pro-inflammatory state, two factors the new geographical discoveries of the fifteenth and
that increase the risk of developing type 2 diabetes and sixteenth centuries allowed a large availability of spices,
diabetic co-morbidities, such as ischemic heart disease, but the great abundance of scents and flavors that
stroke, neuropathy, nephropathy, and retinopathy. Type invested the tables of that epoch, later provoked a tired-
2 diabetes (the most common form of this disease) is one ness towards them and, consequently, a gradual reduc-
of the world’s fastest growing metabolic diseases. It is tion in their use, especially in France and in Italy, where
often, but not always, associated with obesity, which the spices were largely replaced with aromatic herbs,
itself can cause insulin resistance and lead to elevated such as garlic, rosemary, sage, laurel, thyme, oregano,
blood sugar levels. Type 2 diabetes has evolved in asso- and marjoram. These herbs are also used in significant
ciation with cultural and social changes, aging popula- amounts in the Mediterranean diet, a diet associated
tions, increasing urbanization, dietary changes, reduced with a reduced incidence of diabetes and other chronic
physical activity, and other unhealthy lifestyle factors. pathologies, such as heart disease and cancer.
In industrialized countries, along with the aging of the Even nowadays some spices and culinary herbs play
population and the increasing prevalence of obesity, the an important role in primary health care and in the treat-
incidence of diabetes has increased steadily in the last ment of diabetes, especially in developing countries
decades. [2]. Recently, they have been recognized as sources of

Diabetes: Oxidative Stress and Dietary Antioxidants. 89


http://dx.doi.org/10.1016/B978-0-12-405885-9.00009-7 Copyright © 2014 Elsevier Inc. All rights reserved.
90 9.  ANTIOXIDANT SPICES AND HERBS USED IN DIABETES

various phytochemicals, many of which possess a high storage and cooking, but also in the course of diges-
antioxidant activity, which, however, can be affected by tion. Moreover, in the gastrointestinal tract, spices
various factors such as variety, and growing and stor- and culinary herbs can also have another anti-diabetic
age conditions. In particular, almost all spices and the effect because of their ability to decrease the activity
majority of culinary herbs are rich in polyphenols, plant of digestive enzymes, including α-amylase and disac-
secondary metabolites having high antioxidant activity charidases [3,10,11], and, as a result, post-prandial
[3–5] arising from their ability to scavenge a wide spec- hyperglycemia.
trum of free radicals, chelate redox-active metals, and/or The aim of this chapter is to discuss the antioxidant
quench singlet oxygen [4]. They are also known to play activity and the potential anti-diabetic role of some herbs
an important role in stabilizing lipid peroxidation and and spices used to flavor foods, such as sage, marjoram,
in inhibiting various types of oxidizing enzymes [6]. In oregano, peppermint, thyme, garlic, laurel, ginger, tur-
addition, most of these phenolic compounds have anti- meric, cumin, coriander, mustard, and pepper.
microbial properties that together with their antioxidant
capacity are a valuable aid in food preservation. Spices
and culinary herbs also possess a high anti-glycant CULINARY HERBS
potential arising mainly from their polyphenol content
[7]. The non-enzymatic glycation of proteins (Maillard
Lamiaceae
reaction) is a process closely linked to oxidative stress
and is associated with increased production of hydro- The family of Lamiaceae or Labiatae includes several
gen peroxide and other highly reactive oxidants that widely used culinary herbs, such as sage, oregano, pep-
in turn leads to the formation of complex compounds, permint, marjoram, thyme, and basil. These herbs are
the advanced glycation end-products (AGEs), which particularly rich in phenolic compounds (Table 9.1) which
alter the structure and functions of proteins. AGEs are possess a high antioxidant capacity [5,12], anti-glycant
involved in the pathogenesis of diabetes, and contrib- action (Table 9.2) and other beneficial properties, such as
ute to several pathophysiologies associated with aging anti-inflammatory and anticancer activities [13]. In addi-
and diabetes mellitus, such as chronic renal insufficiency, tion, they can affect glycemia by acting on several factors
Alzheimer's disease, nephropathy, neuropathy, and cat- which influence glucose homeostasis (Table 9.3). Along
aract [7]. Hyperglycemia accelerates the formation of with basic plant antioxidants, culinary herbs of Lamiac-
AGEs and the degree of accumulation of AGEs is corre- eae contain specific characteristic antioxidants (Table 9.1),
lated to the severity of diabetic complications [7]. such as lamiatic acid, carnosic acid, carvacrol, and various
Most polyphenols maintain the main features of their methyl and ethyl esters of these substances and deriva-
structure even after ingestion and metabolism; however, tives of phenolic acids, such as rosmarinic acid, one of
the stability and bioavailability of these secondary plant the most effective antioxidant compounds in these plants
metabolites could be affected by several factors [8]. More- [4,14]. Both extracts and isolated antioxidant compounds
over, most polyphenols are poorly absorbed by humans from these herbs have been shown to possess potential
and the real concentrations that can be reached in plasma anti-diabetic properties.
of individuals subjected to a reasonable polyphenol con- Sage (Salvia officinalis L) is a member of Salvia, the larg-
sumption are transient, because of the rapid metabolism est genus of the Lamiaceae’s family which includes about
of these compounds, and are more modest (nanomolar 900 species, spread throughout the world. Many species
range) than those of other plasma antioxidants (micro- of Salvia have been used as traditional herbal medicines
molar range) [8]. However, as a consequence of this low against several diseases, but sage has been one of the most
bioavailability, these compounds can be present in the commonly used plants in folk medicine since antiquity,
gastrointestinal tract at much greater concentrations. as indicated by its Latin genus name Salvia, meaning ‘to
The gastrointestinal tract is an important site of reactive cure’ and species name officinalis, meaning ‘medicinal’.
species production because is much more exposed than The plant is reported to have a wide range of biological
other tissues to pro-oxidants, such as hydroxyl radicals activities, including anti-oxidative properties [15], hypo-
generated in the stomach by the interaction of copper glycemic [16] and anti-inflammatory effects [11]. The
and iron contained in foods and ascorbic acid from diet beneficial effects of sage are the result of numerous com-
and/or gastric juice, oxidized lipids derived from foods pounds from diverse chemical groups acting together,
or from lipid peroxidation in the gastrointestinal tract, including many phenolic compounds of which the
nitrous acid and nitrosamines originated by nitrites, and main is rosmarinic acid [14]. Several studies have dem-
reactive species produced by immune system [9]. There- onstrated that sage has high in vitro antioxidant activity
fore, the seasoning of foods with spices and/or culinary [3,6,11,14,15,17,18], mainly due to its phenolic compounds.
herbs, by increasing antioxidant contents of meals, can Moreover, sage tea has been shown to improve liver gluta-
reduce the production of pro-oxidants not only during thione levels in mice and rats [19]. In addition, Lima et al.

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Culinary Herbs 91
TABLE 9.1  Major Antioxidant and Active Compounds of Culinary Herbs
Major Antioxidants and Active Compounds

Sage (Salvia officinalis) Ascorbic acid, beta carotene, beta-sitosterol, camphene, carnosic acid, carnosol,
Family Lamiaceae gamma-terpinene, hispidulin, labiatic acid, oleanolic acid, terpinen-4-ol, ursolic
acid, selenium [4], salvigenin, nevadensin, apigenin, cirsileol, cirsimaritin

Oregano (Origanum vulgaris) Camphene, carvacol, gamma-terpinene, thymol, terpinen-4-ol, myricene,


Family Lamiaceae linalyl-acetate [4]

Marjoram (Origanum majorana) Ascorbic acid, beta carotene, caffeic acid, rosmarinic acid, tannin, eugenol,
Family Lamiaceae hydroquinone, myrcene, phenol, terpinen-4-ol, trans-anethole, ursolic acid,
beta-sitosterol, oleanolic acid [4]

Peppermint (Mentha x piperita ) Ascorbic acid, beta carotene, narirutin, eriodictyol, eriodictyol 7-O-β-
Family Lamiaceae glucoside, eriocitrin, hesperidin, isorhoifolin, luteolin 7-O-β-glucoside,
luteolin 7-O-rutinoside, diosmin, rosmarinic acid, caffeic acid, piperitoside,
menthoside, lithospermic acid [26]

Thyme (Thymus vulgaris) Ascorbic acid, beta carotene, isochlorogenic acid, labiatic acid, p-coumaric acid,
Family Lamiaceae rosmarinic acid [4]

Garlic (Allium sativum) caffeic, vanillic, p-hydroxybenzoic, and p-coumaric acids [37], allicin [33]
Family Liliaceae

Onion (Allium cepa) Quercetin, kaempferol, cyanidin glucosides, peonidin glucosides, taxifolin [36],
Family Liliaceae allicin [33]

Laurel or bay leaf (Laurus nobilis L.) Ascorbic acid, beta carotene, tocopherols, eugenol, methyl eugenol,
Family Lauraceae eudesmol [48] kaempferol, kaempferol-3-rhamnopyranoside, kaempferol-3,7-
dirhamnopyranoside, 8-cineole, α-terpinyl acetate, terpinen-4-ol, catechin,
cinnamtannin B1[47]

For more details see the text and the bibliographic references.

TABLE 9.2  Anti-Glycant Activity of Culinary Herbs


Experimental Model Material

Sage In vitro Water extracts [3]


In vitro Methanol extracts [3]
In vitro Ethanol extracts [31]

Oregano In vitro Water extracts [22]


In vitro Methanol extracts [22]

Marjoram In vitro Water extracts [3]


In vitro Methanol extracts [3, 23]
In vitro Ethanol extracts [31]
Animal, type 1 diabetes Methanol extracts [23]

Garlic In vitro Water extracts [44]

Onion In vitro Water extracts [44]

For more details see the text and the bibliographic references.

[20] demonstrated dose-dependent anti-diabetic activity streptozotocin-induced increase in the intestinal Na+/glu-
of sage tea comparable to the standard anti-diabetic drug cose cotransporter-1 (SGLT-1). This anti-diabetic effect of
glibenclamide (metformin) in rats [20]. This study dem- Greek sage appears to be due to the modulation of SGLT-1
onstrated that sage significantly reduced fasting plasma trafficking caused by rosmarinic acid [21].
glucose by increasing hepatocyte glucose consumption, Oregano (Origanum vulgare) and marjoram (Oregano
decreasing fasting gluconeogenesis and inhibiting the majorana) are plants traditionally used in diabetes control
stimulation of hepatic glucose production by glucagon. and treatment in North Africa and the Middle East; how-
Greek sage (Salvia fruticosa) tea has been demonstrated ever their anti-diabetic effects have not yet definitively
to prevent the deterioration of glucose homeostasis in been proven. In vitro studies suggest a potential anti-
streptozotocin diabetic rats (one of the most employed diabetic effect of oregano due to its antioxidant content
animal models for type 1 diabetes), by abrogating the [6,10,15,22], anti-glycant capacity [22,23], and inhibition

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92 9.  ANTIOXIDANT SPICES AND HERBS USED IN DIABETES

TABLE 9.3  Hypoglycemic Effects of Culinary Herbs


Experimental Model Proposed Mechanism of Action

Sage Healthy rats Decreased liver gluconeogenesis [20]


Type 1 diabetic rats Intestinal glucose absorption [21]
In vitro Inhibition of α-amylase and α-glucosidase [3]

Oregano In vitro Inhibition of amylase enzymes [24]

Laurel Type 2 diabetic patients Not investigated [49]

Garlic Type 1 diabetic animal models Insulin secretagogues and sensitizing [40]

Onion Type 1 and 2 diabetic patients Glucogenic [46]

For more details see the text and the bibliographic references.

of carbohydrate digesting enzymes [10,24]. An aqueous albeit in large amounts. Both these species of Allium are
extract of marjoram has been shown to have anti-hyper- rich in sulfur-containing compounds that are products
glycemic activity similar to that of the hypoglycemic drug of the transformation of S-alk(en)yl-l-cysteine sulfoxides
sodium-vanadate in streptozotocin diabetic rats [25]. (ACSOs) by the enzyme alliinase and subsequent reac-
The genus Mentha L includes 18 species and about 11 tions. The ACSOs detected in intact onion are S-1-prope-
hybrids, of which the most used and cultivated are Mentha nyl-l-cysteine sulfoxide (1-PeCSO), S-methyl-l-cysteine
spicata (spearmint) and the hybrid Mentha x piperita (pep- sulfoxide (MCSO), and S-propyl-l-cysteine sulfoxide.
permint). Mints are available in all five continents, are used S-2-Propenyl-l-cysteine sulfoxide (2-PeCSO) is the pre-
in traditional medicine for the prevention and therapy of dominant ACSO in garlic, with smaller amounts of
several diseases, and are a well-known herbal remedy used MCSO, 1-PeCSO and S-Ethyl-l-cysteine sulfoxide [32].
for their aromatic, stomachic, choleretic, carminative, and In intact Allium tissues, ACSOs are located in the cyto-
stimulant properties. The most active compounds in mints sol, where they are protected from lysis by alliinase
are the essential oil and polyphenols. The main phenolic stored in vacuoles. Enzyme and substrates react rap-
compounds are phenolic acids and flavonoids [6,26,27]. idly upon disruption of the tissue, and the sulfoxides
Studies on the anti-diabetic effects of mint are scarce, are converted into thiosulfinates, such as allicin [33].
despite their appreciable total phenolic content. Water These thiosulfinates and their derivatives were found
extracts of peppermint have been shown to improve glyce- experimentally to have a wide variety of potential thera-
mia and lipidemia in offspring of streptozotocin-induced peutic effects [32,34,35], including antioxidant and anti-
diabetic rats [28]. Nevertheless, Narendhirakannan et al. inflammatory activities. Onion and garlic are rich also in
[29] have shown that peppermint ethanolic extracts have phenolic compounds (Table 9.1), and onions are among
no effect on insulin, C-peptide levels, and glucose tolerance the most important dietary sources of flavonoids. The
in the same animal model. main flavonoids in onions are quercetin, kaempferol,
Studies on the anti-diabetic effects of Lamiaceae’s myricetin, cyanidin, peonidin, and taxifolin and their
extracts have shown that basil, sage, marjoram, oregano, derivatives [36]. The main phenolic compounds of
and thyme significantly inhibit the activity of α-amylase garlic are phenolic acids, in particular, caffeic, vanillic,
and α-glucosidase, two key enzymes of carbohydrate p-hydroxybenzoic, and p-coumaric acids [37]. More-
digestion, in vitro [3,10,30] and in vivo [30]. Lamiaceae’s over, garlic and onion are able to uptake and accumu-
extracts have also been demonstrated to possess significant late selenium from the soil readily, and use it for the
anti-glycant capacity in vitro [3,22,23,31] and in vivo [23]. biosynthesis of selenocysteine, an amino acid required
Büyükbalci et al. [18], have investigated in vitro the anti- for the synthesis of seleno-proteins, including the anti-
oxidant and anti-diabetic effects of herbal teas traditionally oxidant enzymes glutathione peroxidase, thioredoxin
used in the treatment of diabetes in Turkey, and found that reductase and iodothyronine deiodinases. Many stud-
peppermint and thyme have high antioxidant activity and ies have reported the role of Allium species in the pre-
inhibitory effects on glucose absorption, whereas sage was vention and treatment of several human pathologies,
less effective. including diabetes [38–41], metabolic syndrome [42],
and cardiovascular disease [35,43]. An in vitro anti-
glycant activity has been found both in garlic and
Garlic
onion [44]. Moreover, both garlic and onion have been
Garlic (Allium sativum) and onion (Allium cepa) are shown to have hypoglycemic effects in different ani-
two species widely used for flavoring foods and in folk mal models and in limited human trials [13,40,45,46].
medicine. Onion, though not strictly an herb, is pre- However, recently, a meta-analysis of their anti-diabetic
sented for comparison as it is used in flavoring food, effect in experimental diabetic rats has shown that onion

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Spices 93
TABLE 9.4  Major Antioxidant and Active Compounds of Spices
Major Antioxidants and Active Compounds

Ginger (Zingiber officinalis) 6-Gingerol, 6-shogaol, ascorbic acid, beta carotene, caffeic acid,
Family Zingiberaceae camphene, gamma-terpinene, p-coumaric-acid, terpinen-4-ol [4]

Turmeric (Curcuma domestica) Ascorbic acid, carotenes, caffeic acid, curcumin, p-cumaric-acid [4]
Family Zingiberaceae

Cumin (Cuminum cyminum) Apigenin, luteolin, cuminaldehyde, cuminic alcohol, p-cymene,


Family Apiaceae β-pinene, cuminal, cumin alcohol, γ-terpinene [55]

Coriander (Coriandrum sativum) beta carotene, beta-sitosterol, caffeic acid, camphene, gamma-
Family Apiaceae terpinene, isoquercitrin, myrcene, myristicin, p-hydroxy-benzoic-acid,
protocatechuic-acid, quercetin, rhamnetin, rutin, scopoletin, tannin,
terpinen-4-ol, trans-anethole, vanillic-acid [4]

Mustards (Brassica nigra, alba, juncea) Carotenes, glucosinolates [58]


Family Brassicaceae

Black Pepper (Piper nigrum) Ascorbic acid, beta carotene, ubiquinone, camphen, carvacrol, eugenol,
Family Piperaceae gamma-terpinene, methyl eugenol, piperine [4]

For more details see the text and the bibliographic references.

extracts and single components of both species (S-allyl- TABLE 9.5  Anti-Glycant Activity of Spices
cysteine sulfoxide, S-methylcysteine sulfoxide, and dial-
Experimental Model Material
lyl trisulfide) have significant positive effects on blood
glucose concentration and body weight, while garlic has Ginger In vitro Ethanol extracts [31]
no significant anti-diabetic effects [39]. In vitro Water extracts [44]

Turmeric In vitro Water extracts [44]

Cumin In vitro Water extracts [44]


Laurel (Bay Leaves)
Mustard In vitro Water extracts [44]
Laurel (Laurus nobilis, Family Lauraceae) is used as a
Black Pepper In vitro Water extracts [44]
valuable flavoring agent in the culinary and food indus-
try. This plant is used in folk medicine, in stomachic and For more details see the text and the bibliographic references.
carminative remedies, and for the treatment of digestive
disease. Laurel contains several compounds with antioxi- TABLE 9.6  Hypoglycemic Effects of Spices
dant activity (Table 9.1). Both the water extract and the
Proposed Mechanism
non-polar fraction of leaves have been shown to possess Experimental Model of Action
high antioxidant activity, the former mainly because of its
polyphenol content [47], and the latter for its high levels of Ginger Type 2 diabetic patients Improvement of insulin
and diabetic animal action [51]
terpenes [48]. A clinical trial showing that laurel improves models
glycemia and lipid profiles in type 2 diabetes patients [49]
makes this culinary herb a promising anti-diabetic agent. Turmeric Type 2 diabetic Improvement in insulin
animal models action [53]

Cumin Type 1 diabetic rat Delay of diabetic cataract


[56]
SPICES
Mustards Type 1 diabetic rats Increased serum insulin [58]
Spices are an excellent source of antioxidants [12], and For more details see the text and the bibliographic references.
some of them even outperform synthetic antioxidants
with the advantage of being more secure from the point
Ginger and Turmeric
of view of health. Generally, they contain large amounts
of phenolic substances (Table 9.4), many of which have Ginger (Zingiber officinalis) and turmeric (Curcuma
received great attention with regard to their antioxidant longa) are members of the botanical family of the Zingib-
and anti-inflammatory properties. Among the spices, eraceae (ginger family), whose rhizome is used as a spice.
ginger, turmeric, cumin, coriander, and mustard have Both these spices are among the most commonly used
been reported to have anti-diabetic potential due to their worldwide and are also widely employed in traditional
anti-glycant activity (Table 9.5) and possible blood sugar medicines. Ginger contains several antioxidant com-
lowering effects (Table 9.6). pounds (Table 9.4) [15,50], comprising different phenolic

II.  ANTIOXIDANTS AND DIABETES


94 9.  ANTIOXIDANT SPICES AND HERBS USED IN DIABETES

substances among which are the gingerols (in particular, (parsley family), whose dried seeds are used as a spice.
6-gingerol), the compounds responsible for the pungency Cumin, like turmeric, is a component of curries and is
of the fresh rhizome. Cooking ginger transforms gin- also used as a condiment and flavoring in many orien-
gerols into zingerones, which are less pungent and have tal dishes. These two spices are also widely used in tra-
a spicy-sweet aroma, while drying and thermal treatment ditional medicines and contain high concentrations of
of the rhizome leads to an increase in the concentration of antioxidant compounds, including phenolic acids and
shogaols, the dehydrated form of gingerols, in particular flavonoids [50,54] (Table 9.4), whose antioxidant activ-
6-shogaol. The pungent constituents of the rhizome are ity has been demonstrated in several in vitro and animal
responsible for ginger's anti-nausea action, and its anti- models of oxidative stress [15,50,55]. Cumin and corian-
microbial and antiviral activities. Along with antioxidant der have been demonstrated to exert anti-glycant activ-
properties, ginger has even been shown to possess anti- ity in vitro [44,56,57] and a hypoglycemic action [38,56] in
glycant activity [31,44] and other potential anti-diabetic animal models of diabetes.
effects. In fact, recent data from in vitro, in vivo, and clini-
cal trials showed an anti-hyperglycemic effect of ginger
due to improved insulin signaling and metabolism of Mustards
carbohydrates and lipids [51]. In addition, ginger has Mustards are several plant species in the genera
shown potential protective effects on diabetic complica- Brassica and Sinapis belonging to the Brassicaceae
tions of the liver, kidney, eye, and neural system [44,51]. family whose seeds are used as spices. The most cul-
Turmeric is widely used in cooking and gives the fla- tivated are black mustard (Brassica nigra), white mus-
vor and yellow color to the Indian curry, a mixture of tard (Brassica or Sinapis alba), and oriental or Indian
spices in which turmeric is the major component (about mustard (Brassica juncea). Mustards are used as food
40–50%). It is also used in mustard sauces and for color- flavoring and in traditional medicine as emetics and
ing butter and cheese. Turmeric has been used in tradi- diuretics, as well as a topical treatment for inflam-
tional medicines as an anti-inflammatory agent, to treat matory conditions such as arthritis and rheumatism.
digestive and liver problems, skin diseases, and wounds. Mustard seeds contain numerous chemical constitu-
Turmeric is valued mainly for its principal pigment, cur- ents, including carotenes and phenolic compounds,
cumin, which, along with few other related pigments, but the most investigated are glucosinolates, the thio-
gives the yellow color to the rhizome of the plant. Chem- cyanate glycosides from which derive the spice fla-
ically, these pigments are polyphenols and all together vor. These glucosinolates, when hydrolyzed by the
they are called curcuminoids. Turmeric and, in particu- enzyme myrosinase to flavor-active isothiocyanates,
lar, curcumin have been extensively investigated in the are responsible of the pungency of the spice. Gluco-
last decades for their antioxidant and anti-inflammatory sinolates are typical constituents of Brassica species,
properties [52]. The results of these investigations have which also include broccoli, cabbage, cauliflower,
demonstrated that curcumin is a powerful antioxidant Brussels sprouts, caper, etc. They have been extensively
and immuno-modulant. These activities of curcumin investigated for their potential beneficial effects, espe-
come from its ability to modulate numerous signaling cially as potential anticancer agents, because of their
molecules in humans, such as pro-inflammatory cyto- detoxification activity that derives primarily from
kines, apoptotic proteins, transcription factors (in par- their ability to affect the metabolism of carcinogenic
ticular, NF-κB), cyclooxygenases, lipoxigenases and substances, including several pro-oxidants, through
adhesion molecules [52]. Some promising effects have the modulation of drug-metabolizing enzymes, i.e.,
been observed in patients with various pro-inflamma- the induction of phase II enzymes and the inhibition
tory diseases, including diabetes, diabetic nephropathy of phase I enzymes [58]. The mechanisms of action of
and diabetic microangiopathy [52]. Curcumin has also glucosinolates and related isothiocyanates are multi-
been shown to have an anti-hyperglycemic effect and the ple, and include also antioxidant, anti-inflammatory,
ability to improve insulin sensitivity, and this last action and immuno-modulatory activities [58]. The anti-dia-
has been attributed, at least in part, to its anti-inflam- betic potential of mustard is suggested by a few ani-
matory properties [52,53]. These anti-inflammatory mal studies that have shown a hypoglycemic effect in
properties are also responsible of the beneficial effects of rats of black and oriental mustard [13,59].
turmeric and curcumin on diabetic complications, such
as diabetic nephropathy and microangiopathy [52].
Pepper
Before concluding this section, we would like to
Cumin and Coriander mention also black pepper (Piper nigrum, Family
Cumin (Cuminum cyminum) and coriander (Cori- ­Piperaceae), among the most widespread and most
andrum sativum) are two plants of the Apiaceae family used spice in the world, although it has not yet been

II.  ANTIOXIDANTS AND DIABETES


Summary Points 95
shown that it possesses significant anti-diabetic effects, SUMMARY POINTS
except an anti-glycant activity in vitro [44]. However,
pepper has, in addition to a high antioxidant activity, • O xidative stress increases the risk for developing
other properties that might enhance the anti-diabetic type 2 diabetes and diabetic co-morbidities.
and antioxidant properties of the other spices. The • Spices and culinary herbs contain high concentra-
antioxidant activity of pepper is mainly due to piper- tions of antioxidant compounds, including phenolic
ine, the alkaloid contributing to the pungency of this substances.
spice. Black pepper or piperine treatment has been • The seasoning of foods with spices and/or culinary
demonstrated to inhibit or quench free radicals and herbs increases the daily intake of antioxidants
reactive oxygen species, and to positively influence and protects foods during storage, cooking, and
cellular thiol status, antioxidant molecules and anti- digestion.
oxidant enzymes in vitro, and reduce lipid peroxida- • Spice and culinary herb antioxidants also have other
tion in vivo [60]. In addition, piperine strongly inhibits potential anti-diabetic effects, such as anti-glycant,
hepatic and intestinal aryl hydrocarbon hydroxy- anti-inflammatory and hypoglycemic activities.
lase and UDP-glucuronyl transferase, two enzymes • Further clinical researches are needed to confirm the
involved in both the bio-transforming reactions of real effectiveness of spices and herbs and/or of com-
drugs and phytochemicals, including phenolic sub- pounds isolated from them in diabetes prevention
stances, and the modulation of the bioavailability of and treatment.  
these compounds. In addition, piperine enhances the
bioavailability of a number of therapeutic drugs and
phytochemicals, also through an interaction with the References
ultra-structure of intestinal brush border that causes
[1] Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the preva-
an increase in intestinal absorption of these substances lence of diabetes for 2010 and 2030. Diabetes Res Clin Pract
[60]. The effect of piperine on the bioavailability of 2010;87:4–14.
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Summary Points 97
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