Effect of α-terpinolene on Propionibacterium acnes-induced hyperkeratosis and inflammation in vitro and in vivo.

Acne can impair patients' appearance and even cause psychological disorders such as anxiety and depression. Given the lipase inhibitory activity of the Pinus massoniana L. needles (PMLN) volatile oil, the present study explores the anti-P. acnes efficacy of the PMLN volatile essential oils and the related molecular mechanisms. Common ingredients in the PMLN volatile oil were screened and their anti-P. acnes effects were assessed by MIC test. P. acnes-induced HaCaT cells and mouse acne models validated the efficacy of an active ingredient with strong anti-P. acnes properties for acne treatment, including inflammation and hyperkeratosis. Network pharmacological analysis investigated the mechanism by which this active ingredient exerts its efficacy. Eight active components in the volatile oil of PMLN showed anti-P. acnes activity, with α-terpinolene (Te) having the lowest MIC value. Te suppressed P. acnes-induced release of IL-6, IL-8, IL-1β, and TNF-α from HaCaT cells, accompanied by down-regulation of Ki67, vimentin, and KRT7. Consistently, Te eased pathological changes, inflammatory response, and keratinization in mouse acne models. The targets of Te associated with acne are involved in metabolic pathways, MAPK signaling pathway, NOD-like receptor signaling pathway, and NF-κB signaling pathway. Further experiments validated that Te inhibited the activation of NLRP3 inflammasome and NF-κB signaling in acne lesions of mouse models. Topical treatment with Te alleviates P. acnes-induced dermal inflammation and hyperkeratosis by inhibiting activation of the NLRP3 inflammasome and NF-κB signaling, which provides a new candidate for acne treatment.