Reversal of BCAA-driven inflammatory senescence by traditional herbal oil prevents atopic dermatitis relapse

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease for which effective strategies for achieving sustained remission are lacking. Here, we investigated the efficacy and mechanisms of Liuweirunfu (LWRF) Oil, a traditional Chinese herbal formulation, in preventing AD relapse. RESULTS: A randomized, controlled clinical trial demonstrated that topical LWRF Oil significantly reduced relapse rates and improved clinical outcomes in AD patients during remission (Chictr.org.cn registration number: ChiCTR2400084762). Metabolomic analysis revealed that LWRF Oil restored the skin metabolome by modulating branched-chain amino acid (BCAA) metabolism. Mechanistically, LWRF Oil reversed inflammatory senescence in a murine AD model by selectively enhancing BCAT1-mediated BCAA catabolism, leading to reduced expression of the senescence marker P21. Furthermore, LWRF Oil modulated Th2 cell responses, dampening their infiltration and activation in the skin. CONCLUSIONS: Our findings indicate that LWRF Oil prevents AD relapse by restoring the skin metabolome, reversing BCAA-driven inflammatory senescence, and modulating Th2 cell responses, suggesting it is a safe and effective approach for long-term AD management.