Mechanisms underlying the protective effects of San‐Bai decoction against UV radiation on the skin

Abstract Background San‐Bai decoction (SBD), as a classic TCM formula, has been administered orally to support skin health with a long record history dating back to the Ming Dynasty in China. However, the protective efficacy of SBD through topical application on skin remains unclear. Purpose We aimed to evaluate the effectiveness of SBD in protecting skin against UV radiation through an integrated in silico–in vitro–in vivo framework and elucidate its underlying mechanisms using a systems biology approach. Methods A public database was used to construct a network diagram linking SBD's active chemical components with corresponding potential target genes for network pharmacology analysis. Skin lightening efficacy was evaluated in vitro using a pigmented 3D skin model, while in vivo protective effects were assessed in a double‐blind, placebo‐controlled clinical study. Transcriptomic analysis using the microarray platform was conducted to explore underlying mechanisms among control, UV exposure and SBD treatment groups. Results Network pharmacology analysis implicated over 800 effective targets regulated by SBD, with Gene Ontology enrichment analysis suggesting that they were involved in oxidative response and immune regulation. USBT2627, the aqueous extract of SBD, displayed skin lightening effect in a pigmented living skin equivalent model. Compared with the placebo, pretreatment with 5% USBT2627 effectively protected skin from UV damage, increasing L * values ( p = 0.048) and ITA° ( p = 0.022), and reducing erythema ( p = 0.016). USBT2627 pretreatment also showed a mild effect on a * reduction ( p = 0.052). Transcriptomic analysis indicated that USBT2627 regulated multiple pathways related to skin pigmentation, such as ET‐1 signalling and pigmentation signalling pathways, as well as oxidation response and cytokine signalling pathways. Conclusions USBT2627 suppresses melanin accumulation in vitro and protects skin against UV exposure in both in vitro and in vivo models; multiple components, targets and pathways of SBD act together to confer its protective effect against UV exposure. These findings highlight a significant potential of topical USBT2627 in protecting skin against UV exposure. Additionally, this study showcases the value of a systems network approach in elucidating the mechanisms of this herbal blend, offering valuable references for further research aimed at developing TCM‐based products.