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

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 genes relevant for the development of T2DM A number of candidate genes have been identified in humans and many phytochemicals/extracts from traditional medicinal plants that can target diabetogenic genes have also been identified [135,136].

nations [145]. Despite efforts aimed at containing the disease, no definite cure has been found. Although the current available therapies have yielded appreciable improvements in the quality of life of diabetics, several reports have indicated that such improvements are not without the associated side effects. Studies have confirmed the benefits of medicinal plants with hypoglycaemic effects in the management of diabetes mellitus and many phytomedical preparations and compounds have been touted as candidates for antidiabet‐ ic drug development. However, the rate of developing these drugs is very slow, with only one clinical drug being reported to have gone from plant to pharmacy [110]. Therefore, there should be a focus on developing effective drugs from potent antidiabetic botanicals already identified while further research continues with new plants for the discovery of novel candidates for antidiabetic drugs. Also, potent herbal extracts should be standar‐ dized and made commercially available as many of these extracts often lack the draw‐

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

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Antidiabetic plants do not always have the same mechanism of actions because activities relate to their effects on the pancreatic β cells, the protective/inhibitory effect against insulinase and the increase of insulin sensitivity or the insulin-like activity of the plant extracts. Other mechanisms may involve improved glucose homeostasis, inhibition of intestinal glucose absorption, reduction of glycaemic index of carbohydrates. The mechanisms of action of antidiabetic botanicals need to be properly delineated so that different cases of diabetes can

Further research studies on the antidabetic potentials of botanicals, especially in developing countries, are suggested. The aims of such studies should be to find the botanicals with the most effective antidiabetic activities and to examine the possibilities of developing these active ingredients into antidiabetic drugs for the effective management and treatment of diabetes.

\*Address all correspondence to: akinmoladunfc@yahoo.com; acakinmoladun at futa.edu.ng

1 Phytomedicine, Drug Metabolism and Toxicology Unit, Department of Biochemistry,

2 Drug Metabolism and Toxicology Research Unit, Department of Biochemistry, College of

3 Oxidative Stress Research Centre, Department of Biomedical Sciences, Faculty of Health &

and

Afolabi Clement Akinmoladun1\*, Ebenezer Olatunde Farombi2

School of Sciences, The Federal University of Technology, Akure, Nigeria

Wellness Sciences, Cape Peninsula University of Technology, South Africa

backs associated with single compounds.

be specifically addressed.

**Author details**

Oluwafemi Omoniyi Oguntibeju3

Medicine, University of Ibadan, Nigeria

Medicinal plants can delay or inhibit glucose absorption, facilitate the entry of glucose into cells such as muscle cells, or stimulate insulin secretion by the pancreas. It was reported that oral administration of the ethanolic extract of *Allium sativum* showed significant antidiabetic effect in normal and alloxan-induced diabetic rats and that this effect was probably mediated through the stimulation of insulin secretion from the pancreas [137]. Oral administration of *Gymnena sylvestre* to diabetic rats was reported to increase the number of pancreatic islet cells as well as insulin levels suggesting a possible repair or regeneration of the pancreas [138]. *In vitro* and *in vivo* studies showed that water soluble extracts of *Gymnena sylvestre* released insulin probably due to the regeneration of pancreatic beta cells [139].

Aqueous extract of unripe fruit of *Momordica charantia* showed partial stimulation of insulin release from isolated beta cells of obese hyperglycaemic mice which is an indication of its insulin releasing action as a result of perturbations of membrane functions [140]. *Parinari excelsa* showed hypoglycaemic effects due to its insulin secretory activity in diabetic animal models [141]. Epicatechin which is the active principle isolated from the bark of *Pterocarpus maruspium* showed protective and restorative effect on beta cells of diabetic subjects. This may be due to its ability to regenerate beta cells [139].

Aqueous extract of *Citrullus colocynths* showed a dose dependent increase in insulin released from isolated islets [142]. Immunohistochemistry studies [143] showed that the amount of insulin in beta cells of the islet of Langerhans is greater in *Citrullus colocynthis* treated rats when compared with the control group.

A report on *in vitro* assays on some medicinal plants showed that they possess inhibitory activity on alpha glucosidase enzyme. In a study, thirty seven of forty-five samples examined showed IC50 values of between 2.33 *μ*g/mL and 112.02 *μ*g/mL, which were lower than that of acarbose (117.20 *μ*g/mL) [144]. Also, 80% ethanol extract from *Garcinia daedalanthera* Pierre. leaves (Clusiaceae), *Antidesma celebicum* leaves (Euphorbiaceae), *Amaracarpus pubescens,* (Rubiaceae), and *Willughbeia tenuiflora* leaves (Apocynaceae) had the highest *α*-glucosidase inhibiting activity with IC50 of 2.33 *μ*g/mL, 2.34 *μ*g/mL, 3.64 *μ*g/mL, and 8,16 *μ*g/mL respec‐ tively. Meanwhile, types of enzyme inhibition mechanism from *Garcinia kydia* leaves (Clusia‐ ceae), *Antidesma celebicum* leaves (Euphorbiaceae), and *Amaracarpus pubescens* leaves (Rubiaceae) were non-competitive inhibitor, competitive inhibitor, and mixed inhibitor respectively.
