Protective Effectof Physalis alkekengi Extract on MGO-InducedNonenzymatic Glycation Fibroblasts via ECM-IntegrinInteractions

Abstract Advanced glycation end products (AGEs) and their precursor methylglyoxal (MGO) promote skin aging by disrupting the cellular mechano-environment. This study investigated whether Physalis alkekengi water extract (PAE) could protect this mechanical network and inhibit AGEs’ formation. Among 12 regional samples, PAE from Hami, Xinjiang, most potently inhibited carboxymethyllysine formation. In MGO-damaged cells, this optimal PAE restored cellular stiffness, preserved F-actin structure, and increased secretion of type I collagen and elastin. It upregulated TGF-β1, suppressed MMP-2/9, and enhanced integrin β1-mediated mechanotransduction, thereby elevating key extracellular matrix (ECM) proteins (elastin, fibronectin, laminin-5) and rescuing impaired cell migration and adhesion. We conclude that PAE counteracts skin aging by simultaneously inhibiting glycation and protecting the ECM-cell mechanical network, supporting its potential in functional foods and skincare.