Investigation of the regulatory mechanisms of Zanthoxylum armatum extract on inflammatory responses and lipid metabolism dysregulation in human keratinocytes

Acne vulgaris is a common chronic dermatological condition characterized by abnormal inflammation and disturbances in lipid metabolism. Zanthoxylum armatum DC., a prominent medicinal and edible plant, exhibits anti-inflammatory and antioxidant properties, yet its role in acne-associated pathological processes remains under-explored. This study examined the effects of the ethanolic extract of Z. armatum (Za.E) on inflammation and dysregulated lipid metabolism in keratinocytes. Chemical profiling via UPLC-Q-TOF-MS identified nine major constituents, predominantly terpenoids and a flavonoid. Network pharmacology and molecular docking prioritized AKT1, TNF, and PPARα as central targets, which were validated in LPS/TNF-α-stimulated HaCaT cells. Results demonstrated that Za.E significantly downregulated the mRNA expression of pro-inflammatory genes ( IL-17 A, IL-6, IL-8 , and TNF-α ) and mitigated oxidative stress. Furthermore, Za.E ameliorated lipid accumulation by activating the PPARα pathway and inhibiting SREBP-1-mediated lipogenesis. These findings support the multi-target potential of this functional food ingredient in modulating cutaneous homeostasis.