Antidiabetic bioactive compounds from Tetrastigma angustifolia (Roxb.) Deb and Oxalis debilis Kunth.: Validation of ethnomedicinal claim by in vitro and in silico studies

Tetrastigma angustifolia (Roxb.) Deb is an evergreen shrub belonging to the family Vitaceae. This plant species has been used for thousand years in Ayurvedic medicine. Ethnomedicinal study also documents the use of T. angustifolia leaves in the management of diabetes. On the other hand, Oxalis debilis Kunth. is a tristylous plant commonly known as pink woodsorrel belong to the family Oxalidaceae. This plant has been used traditionally for the treatment of dysentery and diarrhea. Ethnobotanical study also reports the use of leaf decoction of O. debilis in the treatment of diabetes. In our earlier work, the antidiabetic activity of hydro-alcoholic leaf extracts of T. angustifolia and O. debilis have been reported. In spite of ethnomedicinal implications and several scientific studies in the recent past, phytochemical investigations in support of the antidiabetic potential of these plant species are yet to be explored. Therefore, the present study was aimed at the isolation of bioactive phytoconstituents as antidiabetic principle(s) from T. angustifolia and O. debilis leaves. In this paper, two bioactive compounds, namely apigenin derivative (AGD) and stigmasterol (STM) were isolated from the methanolic leaf extracts of T. angustifolia and O. debilis, respectively by column chromatographic technique. The structures of the isolated compounds were established by spectroscopic/ spectrometric techniques including FT-IR, ¹H NMR and ¹³C NMR and Mass. The isolated flavonoids were identified as 8-hydroxyapigenin 7-O-β-D-glucopyranoside, a derivative of apigenin (AGD) and stigmasta-5,22-dien-3β-ol i.e., stigmasterol (STM). The antidiabetic potential of AGD and STM was evaluated by in vitro α-glucosidase and α-amylase inhibitory assays. To validate the antidiabetic efficacy, molecular docking and dynamics studies were performed using AutoDock Vina and GROMACS software. In vitro assays revealed the antidiabetic potential of AGD and STM with α-glucosidase and α-amylase inhibitory activities. From docking and MD simulation studies, promising binding affinity of AGD and STM for human lysosomal α-glucosidase (5NN8) and human pancreatic α-amylase enzymes (1B2Y) with favorable binding modes, stable protein-ligand complexes and well defined protein-ligand interactions were observed. Based on in vitro and in silico studies, our study reports the antidiabetic potential of the isolated apigenin derivative, AGD (a new flavonoid molecule) and stigmasterol, STM (an existing plant sterol) with α-glucosidase and α-amylase inhibitory activities. However, the flavonoid molecule, AGD possesses better antidiabetic profile than the steroid molecule, STM particularly against human α-amylase enzyme. Our present investigation successfully validates the traditional as well as ethnomedicinal claims of T. angustifolia and O. debilis as antidiabetic medicines.