Pipa Qingfei Yin Ameliorates Acne Inflammation in Mice via Suppressing Neutrophil Extracellular Traps

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit driven by Cutibacterium acnes colonization and the ensuing inflammatory response. Neutrophil extracellular traps (NETs) play a critical role in acne inflammation. Pipa Qingfei Decoction (PPQFY), a classic Traditional Chinese Medicine formula for acne, exhibits antibacterial and anti-inflammatory effects, but whether it regulates NETs to alleviate Cutibacterium-induced acne remains unclear. In vitro (keratinocytes/neutrophils) and in vivo (C57BL/6 mice) acne models were established using Cutibacterium acnes and treated with PPQFY, DNase I, or GSK484 (NET inhibitors). Neutrophil purity and Ly6G⁺CD11b⁺ cell ratio were assessed by flow cytometry. Cell viability and proliferation were evaluated using CCK-8 and EdU assays. Levels of IL-1β, TNF-α, and MPO-DNA were measured by ELISA. Protein levels of PADI4, CitH3, and MPO were determined by western blotting. Skin pathological changes were examined by H&E staining. PPQFY reversed Cutibacterium acnes-induced reductions in keratinocyte viability and proliferation and suppressed the elevation of IL-1β and TNF-α. PPQFY also inhibited NET release, as evidenced by decreased levels of MPO-DNA, CitH3, and PADI4. In mice, PPQFY alleviated skin inflammation, reducing keratin thickening, inflammatory infiltration, and Ly6G⁺CD11b⁺cell accumulation. These effects were comparable to those of NET inhibitors. PPQFY ameliorates Cutibacterium acnes-induced acne in mice by regulating NETs, providing a novel mechanistic basis for its clinical use and identifying NETs as a potential therapeutic target for acne.