pubescens seed on CYP3A4 inhibition was also determined. Since antidiabetic herbs are used along with oral hypoglycemic agents, the effect of H. The mechanisms by which this herb reduces blood glucose levels were also determined by evaluating its effect on different physiologic mechanisms involved in glucose homeostasis such as secretion of insulin, glucose metabolism, α-glucosidase enzyme inhibition, and protein glycation. The study determined the hypoglycemic and insulin-secreting effect of the methanolic extract of this herb on oral glucose tolerance test and type-2 diabetes in rats. pubescens seeds for the treatment of type-II diabetes. The present study was carried out to confirm the antidiabetic effect of traditionally used H. None of the studies so far have attempted to identify the phytoconstituents and finally and no attempt was made to understand the mechanism(s) of antidiabetic action of this widely used herbal medicine. The herb is used traditionally in the management of only type-2 diabetes. pubescens administered nicotinamide ( Furman, 2021). Though the administration of nicotinamide before streptozocin to induce diabetes in adult rats is reported to protect some pancreatic insulin-secreting cells, none of the reported studies on H. All the studies in diabetic rats were conducted after the induction of diabetes by a single dose of streptozocin which results in the loss of all pancreatic cells in about 5 days and is a model for type-1 insulin-dependent diabetes mellitus ( Deeds et al., 2011). Several drugs are available in the market for the management of diabetes and each of these drugs acts through different mechanisms ranging from prevention of glucose absorption, increasing insulin secretion, and enhancing glucose transport into the cells( DeFronzo et al., 2019).ĭespite the wide use of this plant in the management of diabetes traditionally, the pharmacological studies reported so far have several flaws. pubescens inhibits glucosidase (Ali et al., 2011b). Another study found that a hydromethanolic seed extract of H. There are several reports on the antidiabetic effect of this herb on streptozocin-induced diabetes (Ali et al., 2011a Hegde and Res, 2014, Keshri, 2012, Kumar and Yadav, 2015, Pathak et al., 2015, Sheikh et al., 2013). pubescens is used traditionally used in the treatment of diabetes ( Ocvirk et al., 2013). Plant products are widely used for the management of diabetes either alone or as supplements with modern drugs ( Ansari et al., 2022, Bindu and Narendhirakannan, 2019). It is also known to act as a memory enhancer (Ali et al., 2011a). The herb has been reported for several pharmacological effects such as antipyretic, antidysentery, antidiarrheal, anthelmintic, antibacterial, and anti-amoebic effects ( Jamadagni et al., 2017). pubescens is widely used in traditional medicine in the treatment of gastrointestinal disorders ( Jamadagni et al., 2017). It is also available in the Middle East where it is popularly known as ‘ the tongue of the bird’. Don, (Family- Apocynaceae) commonly known as Tellicherry bark (English) is a medicinally significant plant native to Africa and Asia's tropical and subtropical areas( Zahara et al., 2020). The herb is devoid of CYP3A4 inhibitory effect indicating that it may not have pharmacokinetic interaction with the drug metabolized by this enzyme. pubescens seed extract increases insulin secretion and inhibits glucose absorption both in-vivo and in-vitro with a weak protein glycation inhibitory effect. However, it had a very weak inhibitory effect on protein glycation and it did not affect the activity of CYP3A4. The extract also inhibited α –glucosidase enzyme activity and demonstrated that it can increase the secretion of insulin from INS to 1-rat insulinoma cell line cells in-vitro in a concentration-dependent manner. It also reduced the serum glucose levels in streptozocin-induced diabetes. The seed extract increased serum insulin levels and reduced serum blood glucose levels in the oral glucose tolerance test. Its potential for herb-drug interaction was evaluated in the cytochrome P450 3A4 (CYP3A4) inhibition assay. The probable mechanism of action was evaluated in-vitro by α - glucosidase inhibition, glucose metabolism in insulinoma (INS-1) cells to reflect secretion of insulin, and protein glycation inhibition. The current work determined the oral hypoglycemic and antidiabetic effects of seed extract in rats. Holarrhena pubescens is widely used in Indian and Chinese medicine in the treatment of diabetes.
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