The Extract of Periplaneta Americana (L.) Promotes Hair Regrowth in Mice with Alopecia by Regulating the FOXO/PI3K/AKT Signaling Pathway and Skin Microbiota

Abstract: (1) Background: Alopecia, a prevalent dermatological disorder affecting over half of the global population, is strongly associated with psychological distress. Extracts from Periplaneta americana (L. PA), a medicinal insect resource, exhibit pharmacological activities (e.g., antioxidant, anti-inflammatory, microcirculation improvement) that align with core therapeutic targets for alopecia. This study aimed to systematically investigate the efficacy and mechanisms of PA extracts in promoting hair regeneration. (2) Methods: A strategy combining network pharmacology prediction and in vivo experiments was adopted. The efficacy of Periplaneta americana extract was validated by evaluating hair regrowth status and skin pathological staining in C57BL/6J mice. Transcriptomics, metabolomics, RT-qPCR, and 16s rRNA techniques were integrated to dissect the underlying mechanisms of its hair-growth-promoting effects. (3) Results: PA-011 significantly promoted hair regeneration in depilated mice via multiple mechanisms: Enhanced skin superoxide dismutase activity and upregulated vascular endothelial growth factor expression; Modulated FOXO/PI3K/AKT signaling pathway and restored skin microbiota homeostasis; Accelerated transition of hair follicles from telogen to anagen phase. (4) Conclusion: PA-011 exerts hair-promoting effects through synergistic modulation of FOXO/PI3K/AKT signaling and skin microbiome. As a novel therapeutic candidate, it warrants further systematic investigation for clinical translation.摘要： (1) 背景：脱发（Alopecia）是一种影响全球超半数人群的常见皮肤病，与心理困扰密切相关。美洲大蠊（Periplaneta americana, L. PA）作为药用昆虫资源，其提取物具备抗氧化、抗炎、改善微循环等药理活性，匹配脱发治疗的核心靶点。本研究旨在系统探究美洲大蠊提取物促进毛发再生的功效与作用机制。 (2) 方法：本研究采用网络药理学预测结合体内实验的研究策略。通过评估C57BL/6J小鼠的毛发生长状态与皮肤病理染色结果，验证美洲大蠊提取物的治疗功效；整合转录组学、代谢组学、实时定量聚合酶链反应（RT-qPCR）及16S核糖体RNA（16S rRNA）技术，解析其促毛发生长的潜在作用机制。 (3) 结果：PA-011可通过多重机制显著促进脱毛小鼠的毛发再生：提升皮肤超氧化物歧化酶（superoxide dismutase, SOD）活性并上调血管内皮生长因子的表达；调控FOXO/PI3K/AKT信号通路并恢复皮肤微生物群稳态；加速毛囊从休止期向生长期的转化。 (4) 结论：PA-011通过协同调控FOXO/PI3K/AKT信号通路与皮肤微生物组发挥促毛发生长作用。作为新型治疗候选药物，其值得开展进一步的系统临床转化研究。