Dihydromyricetin, a principal flavonoid derived from Vine tea, ameliorates spermatogenic dysfunction by repairing the tight junctions of the blood-testis barrier

Dihydromyricetin (DHM), a flavonoid extracted from rattan tea, possesses notable anti-inflammatory and antioxidant properties. This study aims to evaluate the protective effects and underlying mechanisms of DHM on cyclophosphamide (CTX)-induced spermatogenic dysfunction in mice and in vitro. Mice were divided into six groups: a control group receiving a vehicle via gavage; a CTX-treated group administered CTX (120 mg/kg/week) dissolved in normal saline by intraperitoneal injection; CTX plus Levocarnitine (LC) groups receiving 10 mL/kg/day LC via gavage; and CTX plus DHM groups receiving 37.5 mg/kg, 75 mg/kg, and 150 mg/kg of DHM dissolved in saline solution via gavage. Male mice treated with CTX were given DHM for two weeks. DHM significantly improved the morphology of reproductive organs, increased sperm count, motility, and viability, and restored blood-testis barrier (BTB) integrity. Mechanistically, DHM reduced the expression of proteins in the TGF-β3/p38 MAPK pathway, thereby preserving BTB tight junctions. In vitro, DHM increased the viability and reduced apoptosis in acrolein (ACR)-damaged TM4 Sertoli cells, improved cytoskeletal integrity, and upregulated Claudin-11 expression. These findings suggest that DHM ameliorates CTX-induced spermatogenic dysfunction, which is associated with the modulation of the TGF-β3/p38 MAPK signaling pathway, indicating its potential as a promising candidate for the treatment of male infertility. • Dihydromyricetin restored testicular and epididymal morphology and improved sperm count, motility and viability in a cyclophosphamide-induced mouse model of spermatogenic dysfunction. • Dihydromyricetin preserved blood–testis barrier integrity in vivo and attenuated CTX-induced activation of the TGF-β3/p38 MAPK signaling pathway. • In acrolein-injured TM4 Sertoli cells, dihydromyricetin enhanced cell viability, maintained F-actin cytoskeletal organization and upregulated claudin-11 expression. • Dihydromyricetin as a potential nutraceutical candidate for protecting male reproductive function and treating male infertility associated with BTB disruption.