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

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. A strategy combining network pharmacology prediction and in vivo experiments was adopted. The efficacy of a 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. 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; and accelerated transition of hair follicles from the telogen to anagen phase. PA-011 exerts hair-promoting effects through synergistic modulation of FOXO/PI3K/AKT signaling and the skin microbiome. As a novel therapeutic candidate, it warrants further systematic investigation for clinical translation.