Targeting sonic hedgehog (shh) signaling pathways by the concentration-dependent topical resveratrol for protection from cyclophosphamide-induced alopecia in a mouse model.

BACKGROUND

Chemotherapy-induced alopecia (CIA) is a common and inevitable side effect of systemic cancer treatment. There is an urgent need for novel therapies for cancer patients suffering from hair loss to improve their quality of life. This study aimed to investigate the potential protective effect of concentration-dependent topical resveratrol on hair follicles via targeting sonic hedgehog (Shh) signaling and its related downstream regulatory (Sirt-1), proliferative (Ki-67), and apoptotic status (caspase-3 and Bcl-2) pathways in cyclophosphamide-induced alopecia in female C57BL/6 mice model.

METHODS

All animals were subjected to depilation at the start of the experiment, then mice were divided into 5 equal groups as follows: Control group, cyclophosphamide (CPA)-untreated alopecia group, minoxidil (MXL) + CPA-alopecia, Resveratrol low concentration (RSV L10) + CPA-alopecia, Resveratrol high concentration (RSV H80) + CPA-alopecia. The effects of these drugs on hair coverage score, Shh signaling, Sirt-1, proliferation, and apoptosis were assessed.

RESULTS

Low concentration of topical RSV showed a significant increase in hair coverage score. Shh, Sirt-1, immunohistochemical expression levels of Ki-67, and Bcl-2 were significantly elevated, significantly decreasing caspase-3 expression in skin tissue. Moreover, the superiority extended to include histopathological findings and dermatoscopic skin monitoring compared to the groups that received either topical minoxidil 2 % or RSV at high concentration.

CONCLUSION

Topical low-dose resveratrol protects against CIA by activating Shh signaling and modulating follicular proliferative and apoptotic pathways.