In silico and in vitro characterization of Phytolacca latbenia (Moq.): QSAR, phytochemical, and toxicological insights into antiglycation and antidiabetic potential

Abstract

Diabetes and the related comorbidities have been associated with elevated levels of advanced glycation end products (AGEs). The biochemical process of advanced glycation, is believed to be playing a pivotal role in the development of complications. Since there exists a great deal of promise for natural products offering antidiabetic potential, we studied advanced glycation inhibition and anti-diabetic profile of Phytolacca latbenia (Moq). on fractions and the sorted compounds based on the QSAR and molecular docking analysis. The top two bioactive compounds; Kaempferol and Esculentoside G, were further evaluated for the MD simulation studies at 150 ns run, compared with the standard. Among the tested compounds, Kaempferol presented significant binding energies in MM-GBSA (−48.63 Kcal/mol) and MD simulation studies (73 %) with transcriptional regulator 4F5S. Molecular docking studies revealed that kaempferol formed three hydrogen bonds with Val342, Ser343 and Ser453, along with Pi-Pi stacking and Pi-cation interactions with Trp213 and Arg217 residues of the 4F5S protein. Kaempferol also displayed significant α-glucosidase inhibition (IC₅₀ 0.042 ± 2.31 μg/ml) compared to the acarbose (IC₅₀ 0.036 ± 0.31 μg/ml). Almost all of the selected compounds demonstrated adherence to the safety requirements established by ADMET investigation. Liquid–liquid partitioning of the crude methanolic extract with solvents of increasing polarity yielded five solvent fractions;the ethyl acetate fraction (ETOA) obtained by liquid–liquid partitioning of the crude extract with ethyl acetate and water proclaimed substantial results in both the non-oxidative (61 %) and oxidative (58 %) antiglycation assays for thiol group estimation. The ethylacetae fraction (ETOA) demonstrated comparatively strong antioxidant activity, with an IC₅₀ value of 13.25 ± 0.69 μg/ml as determined by the DPPH assay. In α-glucosidase assay, Aqueous fraction demonstrated a considerable inhibition with IC₅₀ value of 0.108 ± 0.32 μg /ml compared to the standard (IC₅₀ 0.083 ± 0.43 μg/ml). The safety assessment revealed a slight decline in HeLa cell viability, dropping from 82 % at a 2.5 % concentration to 69 % at a 10 % concentration over 24 h, relative to the control.Therefore, Phytolacca latbenia (Moq). and its phytocompounds tested inhibit α-glucosidase and Advanced glycation end product-the process that underlie diabetic complications and may therefore holds great promise as therapeutic agent, with no toxicity concern,against diabetes and related comorbidities.