Exploring the Hair Growth-Promoting Effects of Periplaneta americana Extract on Alopecia Areata Mice through Alleviating Skin Inflammation and Modulating Skin Microbiota Based on Systems Pharmacology

Alopecia areata (AA), an autoimmune hair-loss disease due to follicular inflammatory cell infiltration, lacks an ideal cure. the Periplaneta Americana (PA) extract PA-011, a traditional Chinese medicine with anti-inflammatory, antioxidant, tissue-repair-promoting, and immune-regulating properties, was studied for its AA-treating effects. Guided by network pharmacology, AA model mice were treated with PA-011. Hair growth, skin tissue, inflammatory factors, and Wnt protein levels were examined. Transcriptomics, metabolomics, and 16S rRNA sequencing explored the hair-growth-promoting mechanisms. Network pharmacology showed PA-011 could regulate AA-related targets and pathways. PA-011 intervention promoted hair follicle cell proliferation and hair growth in AA mice, reduced skin TNF-α, IL-23, and VCAM-1 expression. Transcriptomics and WB analysis indicated PA-011 downregulated inflammatory genes, activated Wnt3a, and modulated the TGF-β pathway. Metabolomics found PA-011 regulated metabolic pathways. 16S rRNA analysis showed it reversed AA-induced skin microbiota changes, inhibiting pathogens and promoting probiotics. Multi-omics analysis revealed PA-011 regulated skin microbiota and metabolic balance for hair growth. In conclusion, PA-011 alleviates AA by reducing skin inflammation and modulating skin microbiota, suggesting its potential as an AA therapeutic.斑秃（Alopecia areata, AA）是一种因毛囊炎性细胞浸润引发的自身免疫性脱发疾病，目前尚无理想的治疗方案。美洲大蠊（Periplaneta Americana, PA）提取物PA-011作为一种具备抗炎、抗氧化、促组织修复及免疫调节特性的中药，本研究对其治疗斑秃的效果进行了探究。本研究以网络药理学为指导，对斑秃模型小鼠施加PA-011干预，对小鼠的毛发生长状态、皮肤组织、炎症因子水平及Wnt蛋白表达量进行了检测。通过转录组学、代谢组学及16S rRNA测序技术，本研究解析了PA-011促进毛发生长的潜在机制。网络药理学分析结果显示，PA-011可调控斑秃相关的靶点与信号通路。PA-011干预可促进斑秃模型小鼠的毛囊细胞增殖与毛发生长，并下调皮肤组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-23（IL-23）及血管细胞黏附分子-1（VCAM-1）的表达。转录组学与蛋白质免疫印迹（WB）分析表明，PA-011可抑制炎症相关基因的表达，激活Wnt3a通路，并调控转化生长因子-β（TGF-β）信号通路。代谢组学分析显示，PA-011可调控多条代谢通路。16S rRNA测序分析结果表明，PA-011可逆转斑秃诱导的皮肤菌群失衡，抑制致病菌增殖并促进有益菌生长。多组学联合分析揭示，PA-011通过调节皮肤菌群与代谢平衡发挥促毛发生长的作用。综上，PA-011可通过减轻皮肤炎症、调控皮肤菌群改善斑秃症状，提示其具备开发为斑秃治疗药物的潜力。