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

ABSTRACT 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.