Antidiabetic and hepatoprotective potential of whole plant extract and isolated compounds of Aeginetia indica

Abstract

BackgroundAeginetia indica, a perennial herb from the Orobanchaceae family, generally grows as a root parasite and is widely distributed in the forests of South and South-Asian countries. The plant has valuable uses in herbal medicine against various diseases, such as diabetes, liver diseases, and arthritis. Aim of the studyThe present study was designed to investigate the antidiabetic and hepatoprotective effects of the methanol extract of the whole plant of A. indica in a mouse model followed by the isolation of bioactive compounds and their in-silico studies. MethodsThe hepatoprotective effects were evaluated in a paracetamol-induced hepatotoxicity mouse model. The antidiabetic effects were examined by an oral glucose tolerance test and in an alloxan-induced diabetes mouse model. ResultsThe plant extract, at a dose of 400 mg/kg, caused a significant reduction (p < 0.001) in liver enzyme concentrations, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, similar to the effects of standard drug silymarin. The plant extract, at 400 mg/kg, also significantly reduced (p < 0.001) the fasting blood glucose concentration by 27.33 % after 3 h, compared with a reduction of 45.31 % in response to glibenclamide. In the alloxan-induced diabetes model mice, significant reductions (p < 0.05) in elevated glucose concentrations were observed on days 10 and 20 in mice treated with plant extract and glibenclamide. Chromatographic analyses and nuclear magnetic resonance (NMR) studies identified the presence of β-sitosterol, stigmasterol, and oleic acid in the extract. The possible mechanism underlying the antidiabetic effects was revealed by molecular docking analyses examining the binding of β-sitosterol and stigmasterol with sirtuin 4, an NAD-dependent deacylase enzyme that downregulates leucine-induced and glutamate dehydrogenase-induced insulin secretion. The binding affinities between sirtuin 4 and β-sitosterol, stigmasterol, and NAD were found to be −8.6 kcal/mol, −7.2 kcal/mol and −9.5 kcal/mol, respectively, indicating the probable competition between NAD and the isolated components for sirtuin 4. ConclusionThe present study revealed that A. indica exerted protective effects against alloxan-induced diabetes and paracetamol-induced hepatotoxicity in mice, which supports the findings regarding the use of A. indica during traditional medical practice.