Improvements in Insulin Resistance and β-Cells Dysfunction by DDP-4 Inhibition Potential of Withania somnifera (L.) Dunal Root Extract in Type 2 Diabetic Rat

Abstract

The study was aimed to evaluate improvements in insulin resistance and β-cell dysfunction by DPP-4 inhibition potential of W. somnifera (L.) Dunal root extract in type 2 diabetic rats. The experimental design was containing the in-vitro assay of chosen extract for DPP-4 inhibition, in-silico analysis of DPP-4 binding with dominating compound withaferin – A and in-vivo assays, respectively. Diabetes induction made through the administration of the corticosteroid [1.0 mg/Kg] and high sucrose diet, which was calculated by HOMA [Homeostasis model assessment]. Whereas the presence of the Withaferin – A (steroidal lactone) in extract (dominating compound of extract) was confirmed by HPLC isolation in comparison to the standard compound. Consequently, the histopathology of the pancreas and antioxidants of renal and hepatic tissues were assayed by standard methods. The chosen extract showed 77.3 % in-vitro DPP-4 inhibition and -9.18 to -6.16 KD binding energy performed with active sites of DPP-4. The corticosteroid and high sucrose feeding caused significant changes in HOMA-IR = 3.9 ±40 %, HOMA β % = 65.4±4.12 % and HOMA sensitivity = 25.5±1.2 %. The treatment of extract of WS altered significantly (𝑃 ≤ 0.001) to HOMA indices, HbA1c, insulin, and glucose levels. Consequently, significant changes were seen in the histology of pancreas and antioxidants levels in hepatic and renal tissues. Accordingly, the occurrence of withaferin-A was (dominating compound of extract) confirmed from HPLC isolation in comparison to the standard compound. The FT-IR spectra annotated the availability of potent functional groups in the extract. The results illustrated that amelioration of insulin resistance and β-cell dysfunction were conducted as per DPP-4 inhibition potential of W. somnifera root extract. Therefore, it can be concluded that W. somnifera root extract possesses withaferin -A like bioactive compounds having a capacity of DPP-4 inhibition, which can ameliorate insulin resistance and β-cell dysfunction.