Perera PK, Li.Y. Functional herbal food ingredients used in type 2 diabetes mellitus. Pharmacogansy Review 2012:6:37-45
Abstract
From many reports it is clear that diabetes will be one of the major diseases in the coming years. As a result there is a rapidly increasing interest in searching new medicines, or even better searching prophylactic methods. Based on a large number of chemical and pharmacological research work, numerous bioactive compounds have been found in functional herbal food ingredients for diabetes. The present paper reviews functional herbal food ingredients with regards to their anti-diabetic active principles and pharmacological test results, which are commonly used in Asian culinary system and medical system and have demonstrated clinical or/and experimental anti-diabetic effectiveness. Our idea of reviewing this article is to give more attention to these functional food ingredients as targets medicinal foods in order to prevent or slow down the development of type 2 diabetes mellitus.
Functional herbal food ingredients used in diabetes
Allii Sativi Bulbus
The bulbs of Allium sativum L., has a very long folk history of use in a wide range of ailments. It is also alleged to help regulate blood sugar levels. It can reduce glucose metabolism in diabetics, slows the development of arteriosclerosis and lowers the risk of further heart attacks in myocardial infarct patients. [26] Garlic has been found to be effective in lowering serum glucose levels in STZ-induced as well as alloxan-induced diabetic rats and mice. Most of the studies showed that garlic can reduce blood glucose levels in diabetic mice, rats, and rabbits. [27] Aged garlic extract was also effective in preventing hyperglycemia in mice hyperglycemic by immobilization stress. [28] In addition, Liu et al 2005 reported that both garlic oil and diallyl trisulfide improved glycemic control in STZ-induced diabetic rats. [29] Intake of garlic juice resulted in better utilization of glucose in glucose tolerance tests performed in rabbits, while allicin at a dose of 250 mg/kg was 60% as effective as tolbutamide in alloxan-induced diabetic rabbits. [30]
Mechanism of garlic has previously suggested that allicin can enhance serum insulin by effectively combining with compounds like cysteine, which would spare insulin from SH group reactions that are a common cause of insulin inactivation. [30] Another mechanism proposed that the antioxidant effect of S-allyl cysteine sulfoxide, an isolated product from garlic, may contribute to its beneficial effect in diabetes. [31] Another researcher postulated that garlic may act as an antidiabetic agent by increasing either the pancreatic secretion of insulin from the β cells or release of bound insulin. [32] Therefore the hypoglycemic action of garlic could possibly be due to an increase in pancreatic secretion of insulin from β cells, release of bound insulin or enhancement of insulin sensitivity [Figure 1].
Figure 1: Chemical components in Allium sativum L. which involve in anti-hyperglycemic activity. (a) Allicin; (b) S-allyl cysteine sulfoxide
Allii Cepa Bulbus
The bulbs of Allium cepa L. or common onion has a long history of medicinal and culinary use. [33] Also it has been used for many centuries for their pungency and flavoring value, for its medicinal properties. [34] Many people in Asian and African countries use plants for the treatment of diabetes. [35] Onion feeding improved the metabolic status in diabetic conditions, probably because of hypoglycemic and hypo-cholesterolemic effect, [36] mediated diabetic nephropathy by lowering blood cholesterol levels and decreasing lipid peroxidation. [37] Its active principles showed that allyl propyl disulfide and S-methyl cysteine sulfoxide have an anti-diabetic and anti-hyperlipidemic effect, the latter being analogous to glibenclamide and insulin [Figure 2]. [38],[39],[40]
Figure 2: Chemical components in Allium cepa L. which involve in antihyperglycemia. (a) Allyl propyldisulfi de; (b) S-methyl cysteine sulfoxide
Trigonella foenum-graecum (L.)
Trigonella foenum-graecum L. (fenugreek) is cultivated throughout India and in certain regions of China. Its seeds are used as condiment in India, a supplement to wheat and maize flour for bread-making in Egypt, and one of the staple foods in Yemen. Its seeds are also used as herbal medicine in many parts of the world for their carminative, tonic, and aphrodisiac effects. Various reports have demonstrated that fenugreek seeds extracts, powder, and gum of seeds and leaves can lower blood glucose and cholesterol levels in human and experimental diabetic animals. [41],[42],[43],[44],[45] Its activity has been attributed largely to saponins, [46] high-fiber content, [47] the amino acid 4-hydroxyisoleucine, [48] and the major alkaloid trigonelline [Figure 3]. [49]
Figure 3: Chemical components in Trigonella foenum-graecum L. which involve in anti-hyperglycemia. (a) Trigonelline
Psidium guajava (L.)
Psidium guajava L. is a semi-deciduous tropical tree and is widely grown throughout India for its fruit called Guava. Its fruits are rich in dietary fiber associated with natural antioxidant compounds. [50] The fruit contains a high percentage of vitamin C, carotene, vitamin B1, B2, B6, and pectin. [51] The extract of the whole plant of P. guajava excluding roots was reported to be devoid of any antibacterial, antifungal, antiviral, anti-fertility, hypoglycemic, diuretic, and anti-inflammatory activities. [52] Recently, the ripe fruit peel has been found to possess hyperglycemic activity in diabetic patients. [53] Antidiabetic activity based on higher concentration of Mg in the raw fruit peel of P. guajava had been found. [54] The leaves of P. guajava inhibit the increase of plasma sugar level in alloxan-induced diabetic rats, during glucose tolerance test. [55]Flavonoid glycosides such as strictinin, isostrictinin, and pedunculagin are the effective constituents, which have been used in clinical treatment of diabetes to improve the sensitivity of insulin [Figure 4]. [55]
Figure 4: Chemical components in Psidium guajava L., which involve in anti-hyperglycemia. (a) Strictinin; (b) Pedunculagin
Nelumbo nucifera (Gaertn.)
Nelumbo nucifera Gaertn. is a useful medicinal culinary plant. It has been reported that rhizome extract showed anti-diabetic and anti-inflammatory effects. [56],[57] On the other hands; it has recently been used as plain extraction or blend tea to treat obesity in China. [57],[58]Alkaloids isolated from Nelumbo nucifera, including liensinine, daurisoline, neferine, and flavonoids are the main compounds that give medicinal effects [Figure 5]. [59],[60],[61]
Figure 5: Chemical components in Nelumbo nucifera Gaertn. which involve in anti-hyperglycemia. (a) Liensinine; (b) Daurisoline
Stevia rebaudina (Bert.) Hemsl.
Stevia rebaudina (Bert.) Hemsl. has been used in the treatment of diabetes for many years in China and some other parts of the world. In China this plant is used in medicinal teas for treating heartburn and other ailments also. Plant contain stevioside sweetener that reduces postprandial blood glucose levels in T2DM patients, indicating beneficial effects on the glucose metabolism. [62] The plant contain stevioside with the mechanism to stimulate insulin secretion via a direct action on β cells of pancreatic islet, which is considered to have the potential of becoming a new anti-diabetic drug for use in T2DM [Figure 6]. [63],[64]
Figure 6: Chemical components in Stevia rebaudina (Bert.) Hemsl., which involve in anti-hyperglycemia, Stevioside
Prunella vulgaris (L.)
Dried Prunella vulgaris L., is used to make herbal drink to help restore the body to a natural state after eating too many fried foods. It can be used in salads, soups, stews, or boiled as a pot herb. For medicinal purposes, the whole plant is gathered when the flowers bloom, and dried. It has been reported that there is anti-hyperglycemic effect of the ethanol extract of Prunella vulgaris L. in mice. [65] Compound Jiangtangsu had been isolated from this plant and confirmed to have a remarkable effect to lower blood sugar levels in mice with diabetes mellitus induced by alloxan. [66] The possible mechanism of Jiangtangsu is to repair β cells of pancreatic islet to release insulin. Constituents in the P. vulgaris have been identified, such as, phenolic acids (rosmarinic, caffeic.), triterpenoids (methyl oleanolate, methyl ursolate, methyl maslinate), [67],[68],[69] flavonoids (quercetin, campherol, rutin), [70] tannins, and polysaccharide. [71],[72] The anti-hyperglycemic activity of the P. vulgaris may be due to any one or more of the above constituents [Figure 7].
Figure 7: Chemical components in Prunella vulgaris L., which involve in anti-hyperglycemia. (a) Rosmarinic acid; (b) Quercetin
Ganoderma lucidum (Leyss., ex. Fr.)
Mushrooms have a notable place in the folklore throughout the world and in the traditions of many cultures. [73] Ganoderma lucidum is commonly known as a medicinally potent mushroom. It has been widely used in China and other oriental countries for hundreds of years for the treatment of various diseases, including diabetes and cancer. The sporophore of Ganoderma lucidum is used as both tonic nourishment and medicine for care of diabetic patients. Some research results showed that polysaccharides are the active principles for anti-diabetes.[74],[75] Ganoderans A and B have been isolated and confirmed to have a hypoglycemic activity [Figure 8]. [76],[77]
Figure 8: Chemical components in Ganoderma lucidum (Leyss. Ex Franch.), which involve in anti- hyperglycemia, Ganoderic acid
Punica granatum (L.)
Punica granatum (Pomegranate) is a fruit-bearing deciduous shrub or small tree with diverse pharmacological and therapeutic effects. [78]Pericarpium Granati is used to treat diabetes mellitus in some parts of China. Male abortive flowers of Punica granatum are also used for the treatment of diabetes mellitus in India. Oral administration of the aqueous ethanolic extract of Punica granatum flowers led to a significant blood glucose lowering effect in normal, glucose fed and alloxan-induced diabetic rats. [79] The extract of Punica granatum seeds was also reported to have antidiabetic activity; ursolic acid may be the active constituent [Figure 9]. [80]
Figure 9: Chemical components in Punica granatum L., which involve in anti-hyperglycemia, Ursolic acid
Dioscorea opposita (Thunb.)
Dioscorea opposita, "Chinese yam", is native to China. The rhizomes of Dioscorea opposita Thunb., was traditionally used in diets to control Xiaokezheng (diabetes) in China. Researches confirmed that the water decoction of Dioscorea opposita has an anti-hyperglycemic effect to experimental diabetic mice. [81] Polysaccharides were considered to be the active constituents. Chemical component of Dioscorea opposite,dioscin and diosgenin may be the cause for medicinal effects [Figure 10]. [82]
Figure 10: Chemical component in Dioscorea opposita Thunb., which involve in anti hyperglycemia. (a) Dioscin; (b) Diosgenin
Momordica charantia (L.)
Momordica charantia L. is not only a nutritious vegetable, but is also used in traditional medical practices to treat T2DM. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycemic control. Oral administration of the extract, fruit juice or seed powder of Momordica charantia caused a significant reduction in fasting blood glucose and improved glucose tolerance in normal and diabetic animals and in humans. [83],[84],[85],[86],[87],[88],[89] A wide range of compounds have been isolated from Momordica charantia, of which, a polypeptide (p-insulin, was named as "plant insulin"), the sterol glucoside mixture charantin and the pyrimidine nucleoside vicine have been identified as the orally anti-diabetic principles for humans and animals [Figure 11]. [90],[91]
Figure 11: Chemical components in Momordica charantia L., which involve in anti-hyperglycemia. (a) Charantin; (b) Vicine
Murraya koenigii (L.)
Murraya koenigii L. is promising as it is widely and regularly used as a spice for food flavoring and as such it appears to be without any side effects and toxicity. It is also popular in medical usage. Eating, fully-grown curry leaves is beneficial in controlling diabetes and in weight loss. The leaves of Murraya koenigii are also used as a herb in Indian medicine. Their properties include much value as an anti-diabetic and antioxidant. [92],[93] The aqueous extract of Murraya koenigii leaves has been taken to evaluate the hypoglycemic activity in normal and alloxan-induced diabetic rabbits. The findings from this study suggested that the aqueous extract of these leaves may be prescribed as adjunct to dietary therapy and drug treatment for controlling diabetes mellitus. [94] An intense search of the literature has revealed that the stems, leaves, roots, and seeds are potential sources of carbazole alkaloids, which provide the medicinal effect. Some identified alkaloids are Koenimbine, Koenine, Koenigine, Koenidine, Mahanimbine and Mahanine[Figure 12]. [95],[96],[97],[98]
Figure 12: Chemical components in Murraya koenigii L., which involve in anti-hyperglycemia. (a) Mahanine; (b) Koenimbine
Artocarpus heterophyllus (Lam.)
Artocarpus heterophyllus Lam. (jackfruit) is an integral part of common Indian diet and is freely available in Indian and adjoining continents, its medicinal properties are also mentioned in Indian medicine. The plant is reported to possess antibacterial, anti-inflammatory, anti-diabetic, antioxidant and immunomodulatory properties. [99]
Hot water extract of mature jack leaves is recommended by Ayurvedic and traditional medical practitioners as a treatment for diabetes mellitus. [100] Previous studies have indicated that an extract of Artocarpus heterophyllus improves the glucose tolerance in normal human subjects and diabetic patients. [101] Its leaves contains hypoglycemic and hypolipidemic principles that have the potential to be developed further for the treatment of diabetes. [102] The leaves and stem show the presence of sapogenins, cycloartenone, cycloartenol, β-sitosterol, and tannins [Figure 13]. [103]
Figure 13: Chemical components in Artocarpus heterophyllus Lam., which involve in anti-hyperglycemia. (a) Cycloartenone; (b); β-sitosterol
Mangifera indica (L.)
Mangifera indica is one of the most popular of all tropical fruits. Most parts of the tree [Fruit, seeds, pulp, stem bark, roots, and leaves] have medicinal properties. [104] It is native to tropical Asia. The leaves of Mangifera indica were proven for antidiabetic properties using normoglycemic, glucose-induced hyperglycemia and streptozotocin (STZ)-induced diabetic mice. [105] The natural C-glucoside xanthone mangiferin has been reported in various parts of M. indica, which gives the medicinal property. [106] In KK-A y mice, an animal model of type 2 diabetes, mangiferin (90 mg/kg), 7 h after oral administration, decreased the baseline glucose level by 56%. [107] In the same model, mangiferin (30 mg/kg, p.o., once daily followed 30 min. later by exercise (120 min motorized treadmill) for 2 weeks) reduced the blood cholesterol (~40%) and triglyceride levels (~70%) [Figure 14]. [108]
Figure 14: Chemical component in Mangifera indica Lam., which involve in anti-hyperglycemia, Mangiferin
Aegle marmelos (L.) Corr.
Aegle marmelos (bael tree) fruit is eaten fresh or dried. As for other parts of the plant, the leaves and small shoots are eaten as salad greens in many Asian countries. It is a popular medicinal plant in the Ayurvedic and Siddha systems of medicine and folk medicines used to treat a wide variety of ailments. [109],[110] The leaves, fruits, and stems contain skimianinc, sterol and aegelin, lupeol, marmin. In pharmacological trials, both the fruit and root showed anti-amoebic and hypoglycemic activities. [111],[112],[113] A. marmelos would act like insulin in the restoration of blood sugar and body weight to normal levels in rat and was therefore recommended as a potential hypoglycemic agent [Figure 15]. [113]
Figure 15: Chemical components in Aegle marmelos L., which involve in anti-hyperglycemia. (a) Lupeol; (b) Marmin
Curcuma longa (L.)
Curcuma longa L., commonly known as turmeric, has been used as spice and coloring agent with long history. Its rhizomes have been reported to possess anti-diabetic properties in experimental animal models. [114],[115],[116] Researches reported that active ingredient curcumin is the response for anti-diabetic action [Figure 16]. [116]
Figure 16: Chemical components in Curcuma longa L., which involve in anti-hyperglycemia, Curcumin
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