Mechanistic study of the anti-photoaging effects of Mogroside V via the VEGFA/PI3K-Akt signaling pathway in human fibroblasts
Background: UVA-induced photoaging is a major mechanism of skin aging, characterized by excessive reactive oxygen species (ROS) generation, enhanced inflammatory responses, and degradation of the extracellular matrix (ECM). Mogroside V (MV) is a natural bioactive compound derived from Siraitia grosvenorii; however, its protective effects against skin photoaging and the underlying molecular mechanisms remain incompletely understood.Objective: This study aimed to investigate the protective effects of Mogroside V against UVA-induced photoaging damage in human dermal fibroblasts and to elucidate its potential molecular mechanisms.Study Design: An in vitro cell-based model was established using human dermal fibroblasts (HFF-1) exposed to UVA irradiation to evaluate the antioxidant, anti-inflammatory, and ECM-protective effects of MV. Multi-omics analysis and molecular interaction approaches were integrated to explore the underlying signaling pathways.Methods: HFF-1 cells were exposed to 3 J/cm2 UVA irradiation and subsequently treated with Mogroside V at concentrations of 25-100 ug/mL. Intracellular ROS levels, mitochondrial integrity, and NF-kappaB activation were assessed. The expression levels of pro-inflammatory cytokines IL-1beta, IL-6, and IL-8 were determined, along with changes in matrix metalloproteinase-1 (MMP-1) and ECM-related proteins including elastin and fibronectin. Key signaling pathways were identified through transcriptomic profiling and network pharmacology analysis. Molecular docking and surface plasmon resonance (SPR) assays were performed to validate the interaction between MV and VEGFA.Results: Mogroside V significantly reduced UVA-induced intracellular ROS accumulation, preserved mitochondrial integrity, and inhibited NF-kappaB activation, leading to decreased production of IL-1beta, IL-6, and IL-8. In addition, MV suppressed MMP-1 expression while promoting the expression of ECM components such as elastin and fibronectin. Transcriptomic and network pharmacology analyses identified the PI3K-Akt signaling pathway as a key regulator of these protective effects. Molecular docking and SPR experiments further confirmed a strong binding interaction between MV and VEGFA.