Integrating zebrafish model and network pharmacology for screening and identification of edible herbs with therapeutic potential of anti-photoaging: A promising drug Gentiana rigescens Franch.

Gentiana rigescens Franch. extract have demonstrated various important bioactivities, however, their potential against photoaging has yet to be evaluated. This study explored the anti-photoaging effects of Gentiana rigescens Franch. root extract (GRFR) and stem (GRFS), along with their underlying mechanisms and bioactive components, using the UVB-induced zebrafish model. GRFS demonstrated superior anti-photoaging efficacy compared to GRFR. GRFS significantly alleviated UVB-induced tail fin damage, increasing the relative tail fin area from 31.23% to 80.92% (at 1mg/mL), and reducing ROS levels from 244.80% to 150.95%. It also inhibited lipid peroxidation, lowering malondialdehyde (MDA) levels from 202.87 nmol/g to 142.83 nmol/g. Furthermore, GRFS enhanced antioxidant enzyme activities, increasing superoxide dismutase (SOD) from 80.94 U/g to 104.06 U/g. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) indicated substantial distinctions in the composition and content of major constituents between GRFR and GFRS, which may explain the differences in their anti-photoaging activities. And then network pharmacology was used to investigate possible mechanisms of GFRS, which identified five potential targets including CTNNB1, ESR1, AKT1, JUN and EGFR, as well as three key active compounds including aspartyl-phenylalanine (Asp-Phe), N-acetyl-L-phenylalanine (N-Acetyl-L-Phe), and phenylalanyl-tyrosine (Phe-Tyr). Finally, the molecular docking revealed that Phe-Tyr exhibited the strongest binding affinity for AKT1 (-8.86 kcal/mol), indicating that it may be the most potent anti-photoaging compound in GFRS. These findings suggest that G . rigescens , with its potent anti-photoaging properties, offers superior protection against UVB-induced photoaging and holds promise as a natural therapeutic agent.