**7. Botanicals and their antidiabetic property**

Many medicinal plants have ethnomedical claims of usefulness in the treatment of diabetes worldwide and have been employed empirically in antidiabetic and antihyperlipidemic remedies. Hundreds of plants with antidiabetic and hypoglycaemic activities have also been reported in literature. Despite this, studies on plants with these activities are still necessary. This is because a large percentage of plants are yet to be explored for their medicinal properties. Also, successful antidiabetic drug development from investigated plants is still largely absent although numerous dietary supplements have been formulated. Plants contain glycosides, alkaloids, terpenoids, anthocyanins, tocopherols, flavonoids, carotenoids, polyphenols, peptidoglycans, steroids, coumarins and other constituents that are frequently implicated as having antidiabetic activities [107]. The antidiabetic activities could be obtained from several parts of the plants - aerial parts, bark, flower, root, seeds, leaves, bulb, tubers and/or whole plant [108].

Many studies have confirmed the benefits of medicinal plants with hypoglycaemic effects in the management of diabetes mellitus. The plant families most studied for their hypoglycaemic effects include: Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae, Euphorbiaceae and Araliaceae [109]. The effects of these plants may delay the development of diabetic complications and correct the metabolic abnormalities. During the past few years, efforts at the study of antidiabetic medicinal plants have culminated in the isolation and characterization of single bioactive compounds and the preparation of herbal extracts and multiherbal products. Interestingly, some of these extracts and herbal prepara‐ tions have shown significant insulinomimetic and antidiabetic activities with more efficacy than conventional hypoglycemic agents [13]. For this paper, we shall briefly consider the antidiabetic potential of few of these botanicals.

#### **7.1. Fenugreek**

Leaves, seeds or the entire plant of *Trigonella foenum-graecum* L. (fenugreek) are used for the treatment of diabetes in many countries of the world and several human studies have con‐ firmed the efficacy of the plant. The beneficial effect of the plant has been partly attributed to the high fibre content. The proposed mechanism of action was related to the inhibition of diffusion or transport of glucose independent of hormonal mechanisms [110].

#### **7.2.** *Gymnema sylvestre*

that are medically active. These non-nutrient plant chemical compounds or bioactive compo‐ nents are often referred to as phytochemicals ('phyto-' from Greek - *phyto* meaning 'plant') or

Phytochemicals have been isolated and characterized from fruits such as grapes and apples, vegetables such as broccoli and onion, spices such as turmeric, beverages such as green tea and red wine, as well as many other sources [105]. The WHO estimates that approximately 80% of the world's inhabitants rely on traditional medicine for their primary health care [106].

Many medicinal plants have ethnomedical claims of usefulness in the treatment of diabetes worldwide and have been employed empirically in antidiabetic and antihyperlipidemic remedies. Hundreds of plants with antidiabetic and hypoglycaemic activities have also been reported in literature. Despite this, studies on plants with these activities are still necessary. This is because a large percentage of plants are yet to be explored for their medicinal properties. Also, successful antidiabetic drug development from investigated plants is still largely absent although numerous dietary supplements have been formulated. Plants contain glycosides, alkaloids, terpenoids, anthocyanins, tocopherols, flavonoids, carotenoids, polyphenols, peptidoglycans, steroids, coumarins and other constituents that are frequently implicated as having antidiabetic activities [107]. The antidiabetic activities could be obtained from several parts of the plants - aerial parts, bark, flower, root, seeds, leaves, bulb, tubers and/or whole

Many studies have confirmed the benefits of medicinal plants with hypoglycaemic effects in the management of diabetes mellitus. The plant families most studied for their hypoglycaemic effects include: Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae, Euphorbiaceae and Araliaceae [109]. The effects of these plants may delay the development of diabetic complications and correct the metabolic abnormalities. During the past few years, efforts at the study of antidiabetic medicinal plants have culminated in the isolation and characterization of single bioactive compounds and the preparation of herbal extracts and multiherbal products. Interestingly, some of these extracts and herbal prepara‐ tions have shown significant insulinomimetic and antidiabetic activities with more efficacy than conventional hypoglycemic agents [13]. For this paper, we shall briefly consider the

Leaves, seeds or the entire plant of *Trigonella foenum-graecum* L. (fenugreek) are used for the treatment of diabetes in many countries of the world and several human studies have con‐ firmed the efficacy of the plant. The beneficial effect of the plant has been partly attributed to the high fibre content. The proposed mechanism of action was related to the inhibition of

diffusion or transport of glucose independent of hormonal mechanisms [110].

**7. Botanicals and their antidiabetic property**

antidiabetic potential of few of these botanicals.

phytoconstituents.

148 Antioxidant-Antidiabetic Agents and Human Health

plant [108].

**7.1. Fenugreek**

Extracts of *G. syvestre* have been reported to demonstrate antidiabetic activity possibly via reduction in insulin requirement by enhancing endogenous insulin availability, improv‐ ing vitiated blood glucose homeostasis, better control of hyperlipidemia associated with diabetes, reduction in amylase activity in serum and, increase in *β*-cell function as shown by higher levels of serum C peptide. Extract of the leaves of the plant produced a signifi‐ cant reduction in blood glucose, glycosylated haemoglobin and glycosylated plasma proteins, with a decrease in conventional drug dosages. Some patients were able to discontinue conventional drugs and even maintain their blood glucose homeostasis with extracts alone in T2DM patients [111,112].

#### **7.3.** *Morinda lucida*

Alcoholic and aqueous extracts of roots and leaves of *Morinda lucida* Benth (Rubiaceae) have been reported to possess remarkable antidiabetic property in alloxan- and streptozotocin (STZ)-induced diabetic rats. Suggested mechanisms of action include the stimulation of beta cells to release insulin [113, 114].

#### **7.4.** *C. chinensis* **Franch,** *Astragalus membranaceus***, and** *Lonicera japonica*

Using scientifically validated animal models in a study, a multicomponent berberinecontaining remedy comprising *C. chinensis* Franch*, Astragalus membranaceus*, and *Lonicera japonica* was used to treat male Zucker diabetic fatty rats. The three-herb medicine showed sustained glucose-lowering effects for 1 week after a single-dose treatment. Two-week treatment attenuated insulin resistance and fatty degeneration, with hepatocyte regenera‐ tion lasting for 1 month posttreatment. The beneficial effects were found to have persist‐ ed for 1 year after 1-month treatment and were associated with activation of AMPK, Akt, and insulin-like growth factor-binding protein (IGFBP)1 pathways, with downregulation of miR29-b and expression of a gene network implicated in cell cycle, intermediary, and NADPH metabolism with normalization of CYP7a1 and IGFBP1 expression. Authors concluded that the pluripotent effects of the medicine in altering gene expression, in part through changes in miRNA, explained its sustained beneficial effects on glucose metabo‐ lism, fatty liver, and cellular repair [115].

#### **7.5.** *Pterocarpus marsupium*

A crude extract (water decoction) of *P. marsupium* was reported to have protective and restorative effect on *β*-cells in alloxan-induced diabetic rats. The results were substantiated by histological observations. Various active principles responsible for the antidiabetic activity have been isolated [116,117].

### **7.6. Kolaviron**

Kolaviron, a biflavonoid complex isolated from *Garcinia kola* possesses multiple biological activities. Kolaviron demonstrated significant hypoglycaemic effect when administered to alloxan diabetic rabbits. The blood sugar was lowered from 506 mg/100 mL to 285 mg/100 mL at 12 h after the administration of 100 mg/kg kolaviron. Kolaviron also inhibited rat lens aldose reductase (RLAR) activity, with an IC50 value of 5.4 x 10-6 [118]. Adaramoye and Adeyemi reported that fractions obtained from kolaviron reduced blood sugar levels in STZ-diabetic rats within 4 h of oral administration and showed favourable effect on the plasma lipid profile of diabetic animals [119]. In addition to its antidiabetic property, kolaviron showed remarkable protective effects on cardiac, renal and hepatic tissues of STZ-diabetic rats. Many antidiabetic drugs do not offer significant tissue-protective effect in diabetic animals [120].

beneficial synergistic effect was postulated to be exerted via oxidative stress attenuation, insulin mimetic action and β-cell regeneration. The synergistic postprandial blood glucose modulatory properties of *V. amygdalina*, *Gongronema latifolium* and *Occimum gratissimum* aqueous decoctions has also been reported [127]. It was concluded from the study that the decoction containing the three vegetables was superior in activity to any one or blends of only

Antidiabetic Botanicals and their Potential Benefits in the Management of Diabetes Mellitus

http://dx.doi.org/10.5772/57339

151

*Moringa oleifera* is a popular food plant with multiple medicinal uses including treatment of diabetes [128]. Various parts of the plant have been shown to have antidiabetic potential in several studies. In severely diabetic animals, 200 mg/kg aqueous leaf extract of *M. oleifera* reduced fasting blood sugar by 69.2% after 21 days of treatment and also significantly reduced urine sugar [129]. The progression of diabetes was significantly reduced in STZ-diabetic rats treated with methanol extract *M. oleifera* pods for 21 days with treated animals showing a significant reduction in serum glucose and nitric oxide, with concomitant increases in serum insulin and protein levels [130]. It has also been shown that extracts of the bark of the plant

In a study which assessed the effects of pinitol supplementation on glucose tolerance and insulin sensitivity, investigators found that a single dose of pinitol, from a naturally-occurring food ingredient, administered acutely influences indices of whole-body glucose tolerance and insulin sensitivity in healthy subjects. The study showed that consumption of a pinitolenriched beverage, containing a dose of 6.0 g, reduced the increase in glycaemia and insuli‐ naemia provoked by oral carbohydrate over-load when compared with a placebo. They remarked that this dietary intervention would be an effective first-step strategy for treating hyperglycaemia and related insulin resistance states, although future research is warranted to evaluate whether chronic doses of pinitol are effective in subjects with altered glucose metabolism [132]. Inositol phosphoglycans (IPG) have been reported to be important postreceptor mediators of insulin action [133,134] and it was suggested that by acting as insulin's

Antidiabetic botanicals have been reported to foster protection via several mechanisms. These include amelioration of oxidative stress, anti-inflammatory and antiatherogenic effects; control of metabolic fluxes among various organs and energy metabolism within individual tissues and cells leading to the maintenance of glucose and lipid homeostasis and stable levels of energy stores; cytoprotection of pancreatic β-cells; inhibition of aldose reductase; improvement of endothelial dysfunction; inhibition of angiogenesis and the regulation of the expression of

prevented dexamethasone-induced insulin resistance in peripheral tissues [131].

two, of the three decoctions.

**7.10. Pinitol (3-O-methyl-D-chiro-inositol)**

second messenger, pinitol could increase insulin sensitivity.

**8. Mechanisms of action of antidiabetic botanicals**

**7.9.** *Moringa oleifera*
