ABSTRACT Chemotherapy‐induced skin and hair follicle damage, driven in part by miRNAs such as miR‐204 and miR‐375 that regulate apoptosis and autophagy after alkylating agent exposure, significantly impacts patient quality of life. While chrysin—a common food‐derived flavonoid and nutritional bioactive with antioxidant and cytoprotective properties—has shown potential to modulate miRNA activity, its role in melphalan‐induced injury and associated miRNA expression remains unclear. This study investigated the effects of melphalan on skin and hair follicle integrity in rats, focusing on miR‐204 and miR‐375 expression, and evaluated the protective potential of chrysin treatment. Forty‐eight male Wistar rats were divided into six groups receiving melphalan (1.5 mg/kg), chrysin (50 or 75 mg/kg), or their combination for 21 days. Dorsal skin samples were analyzed using histological and morphometric assessments. Expression levels of apoptosis‐related genes, autophagy markers, and miR‐204/miR‐375 were quantified by RT‐qPCR. Melphalan significantly reduced epidermal thickness and anagen‐phase hair follicles while increasing apoptosis markers (BAX, caspase‐3) and suppressing autophagy‐related genes. It also markedly upregulated miR‐204 and miR‐375. Chrysin co‐administration, particularly at 75 mg/kg, correlates with restored epidermal thickness, improved hair follicle cycling, enhanced autophagy marker expression, suppressed apoptosis, and significantly downregulated miR‐204 and miR‐375. Chrysin reduces melphalan‐induced skin and hair follicle damage, possibly correlating with modulation of apoptosis and autophagy pathways and suppression of miR‐204 and miR‐375. These findings suggest chrysin as a promising nutraceutical candidate and supportive dietary strategy to help reduce chemotherapy‐associated dermatological side effects.
Moghimian et al. (2026) studied this question.