Therapeutic potential of orally administered Connarus semidecandrus Jack ethanol extract in an androgenetic alopecia model

Background Androgenetic alopecia (AGA) is largely driven by the conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase, followed by activation of androgen receptor (AR) signaling. In this study, we evaluated the therapeutic potential of Connarus semidecandrus Jack ethanol extract (CE) as an orally administered intervention for AGA. Methods A testosterone propionate (T.P.)–induced AGA mouse model was used to assess the efficacy and safety of CE. Oral (300 mg/kg) and topical (10 mg/kg) administration of CE were evaluated and compared with finasteride. Hair growth parameters, histological changes, apoptosis-related markers, and AR-associated mediators were analyzed. Systemic toxicity was assessed in the liver and kidney. Phytochemical profiling was performed using high-performance liquid chromatography (HPLC) and quadrupole time-of-flight liquid chromatography–mass spectrometry (QTOF LC–MS), followed by in vitro assays and molecular docking analysis. Results CE treatment promoted hair regrowth with effects comparable to finasteride. CE restored hair shaft thickness, improved hair type distribution, and reduced follicular apoptosis. These effects were accompanied by increased Bcl-2 expression and decreased cleaved caspase-3 levels. CE also reduced AR expression and downregulated AR-associated mediators, including DKK-1, TGF-β1, and IL-6. Oral CE administration for three weeks did not induce detectable hepatotoxicity or nephrotoxicity. Phytochemical analysis identified several flavonoids, including miquelianin, hyperoside, isoquercitrin, and quercitrin. These compounds exhibited inhibitory activity in a 5α-reductase assay and reduced AR expression in vitro , and molecular docking suggested favorable binding of miquelianin to 5α-reductase type 2. Conclusion These findings suggest that CE may represent a safe, naturally derived candidate for further development as an oral therapeutic or functional food for AGA management.