Study of the mechanism by gentiopicroside protects against skin fibroblast glycation damage via the RAGE pathway

The occurrence of nonenzymatic glycosylation reactions in skin fibroblasts can lead to severe impairment of skin health. To investigate the protective effects of the major functional ingredient from Gentianaceae, gentiopicroside (GPS) on fibroblasts, network pharmacology was used to analyse the potential pathways and targets underlying the effects of GPS on skin. At the biochemical and cellular levels, we examined the inhibitory effect of GPS on AGEs, the regulation by GPS of key ECM proteins and vimentin, the damage caused by GPS to the mitochondrial membrane potential and the modulation by GPS of inflammatory factors such as matrix metalloproteinases (MMP-2, MMP-9), reactive oxygen species (ROS), and IL-6 via the RAGE/NF-κB pathway. The results showed that GPS can inhibit AGE-induced damage to the dermis via multiple pathways. The results of biochemical and cellular experiments showed that GPS can strongly inhibit AGE production. Conversely, GPS can block AGE-induced oxidative stress and inflammatory responses in skin cells by disrupting AGE-RAGE signalling, maintain the balance of ECM synthesis and catabolism, and alleviate AGE-induced dysfunctions in cellular behaviour. This study provides a theoretical basis for the use of GPS as an AGE inhibitor to improve skin health and alleviate the damage caused by glycosylation, showing its potential application value in the field of skin care.