Sophoricoside, a genistein glycoside from Fructus Sophorae, promotes hair growth via activation of M4 muscarinic AChR in dermal papilla cells.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE Alopecia, or hair loss, refers to ongoing decline of mature hair on the scalp or any other region of the body. Fructus Sophorae, a fruit from Sophora japonica L., contains various phytochemicals, e.g., sophoricoside, that exhibit a broad range of pharmacological effects. The potential functions of herbal extracts deriving from Fructus Sophorae and/or its major phytochemical, sophoricoside, in treating alopecia are probed here. AIM OF STUDY The objective was to determine the ability of Fructus Sophorae extract and sophoricoside in promoting hair growth and it signalling mechanism. METHODS: Molecular docking studies were conducted to measure the binding affinities between sophoricoside and M4 mAChR in the allosteric binding site. The mechanism of Fructus Sophorae and sophoricoside in activating the signalling involving Wnt/ß-catenin and muscarinic AChR was evaluated by using immortalized human dermal papilla cell line (DPC), as well as their roles in promoting hair growth. The activity of pTOPflash-luciferase in transfected DPCs was used to examine the transcriptional regulation of Wnt/ß-catenin-mediated genes. RT-PCR was applied to quantify mRNA expressions of the biomarkers in DPCs responsible for hair growth. The phosphorylated protein levels of Wnt/ß-catenin and PI3K/AKT in DPC were revealed by using Western blot analysis. The culture of ex vivo mouse vibrissae hair follicle was used to evaluate the hair growth after the treatments. RESULTS: The ethanol extract of Fructus Sophorae and sophoricoside activated Wnt/ß-catenin signalling. The result of molecular docking showed a high binding affinity between sophoricoside and M4 mAChR. The effect of sophoricoside was blocked by specific inhibitor of M4 mAChR, but not by other inhibitors of mAChRs. Sophoricoside promoted hair growth in cultured ex vivo mouse vibrissae hair follicle by acting through M4 mAChR. CONCLUSION: The ethanol extract of Fructus Sophorae and sophoricoside activated Wnt/ß-catenin signalling via activation of M4 mAChR. The results suggested beneficial functions of Fructus Sophorae and sophoricoside as a potential candidate in treating alopecia.