Baicalin ameliorates type 2 diabetes by modulating HIF-1α-mediated oxidative stress and apoptosis: A network pharmacology and experimental study
Abstract
This study investigates baicalin, a flavonoid from Scutellaria baicalensis, as a multi-target therapeutic for type 2 diabetes mellitus (T2DM) through cellular experiments, network pharmacology, and molecular docking. Baicalin improves pancreatic β-cell viability, reduces reactive oxygen species (ROS), and attenuates apoptosis/senescence in methylglyoxal (MGO)-induced models. Network pharmacology identifies key targets including HIF-1α, Bax, Bcl-2, and Caspase-3, while molecular docking confirms strong interactions with proteins like AKT1 and HIF-1α, underlying antioxidative and anti-apoptotic mechanisms. Notably, baicalin’s protective effects extend to molecular biomechanical pathways, potentially modulating extracellular matrix (ECM) remodeling and cytoskeletal dynamics. In T2DM, hyperglycemic stress disrupts ECM integrity and mechanotransduction signaling (e.g., integrin-MAPK axis), contributing to β-cell dysfunction. Baicalin’s regulation of ECM components (e.g., collagen, fibronectin) and cytoskeletal proteins (e.g., actin polymerization) may restore cellular mechanical phenotypes, enhancing β-cell survival and insulin secretion. This biomechanical modulation aligns with exercise’s benefits in T2DM, where physical activity improves ECM elasticity and mechanosignaling, complementing baicalin’s antioxidative and anti-apoptotic actions. Our findings highlight baicalin as a novel therapeutic addressing both biochemical and biomechanical hallmarks of T2DM, suggesting a synergistic strategy combining baicalin with exercise to restore metabolic and mechanical homeostasis.
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