Berberine Inhibits Hyperlipidemia-Associated Erectile Dysfunction Through the Mediation of miR-342-3p–Related Pathway

Berberine has been found to improve diabetes-induced erectile dysfunction, but its role and underlying molecular mechanism in hyperlipidemia-associated erectile dysfunction remain unclear. Rats were fed with a high-fat diet to induce a hyperlipidemia erectile dysfunction model. Erectile function of rats was assessed by measuring the number of erections and intracavernosal pressure/mean arterial pressure value. Corpus cavernosum smooth muscle cells were isolated from the cavernosal tissue of rats. Protein levels of apoptosis-related markers and vascular endothelial growth factor A were analyzed by western blot. Quantitative real-time PCR was performed to examine miR-342-3p and vascular endothelial growth factor A expression. Cell proliferation and apoptosis were tested using CCK8 assay, EdU assay, and flow cytometry. Inflammation was assessed by detecting IL-1β and sCD40L levels using ELISA. The interaction of miR-342-3p and vascular endothelial growth factor A was analyzed by dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation. Berberine treatment enhanced the number of erections and intracavernosal pressure/mean arterial pressure value in rats with erectile dysfunction in vivo, as well as promoted proliferation of cavernosum smooth muscle cells, and suppressed apoptosis and inflammation in vitro. Vascular endothelial growth factor A was a target of miR-342-3p, and berberine reduced miR-342-3p expression and promoted vascular endothelial growth factor A expression. Also, miR-342-3p overexpression or vascular endothelial growth factor A knockdown could reverse berberine-induced corpus cavernosum smooth muscle cells growth. Besides, vascular endothelial growth factor A overexpression abolished the inhibitory effect of miR-342-3p. Moreover, injection of adenovirus miR-342-3p eliminated the promoting effect of berberine on erectile function in high-fat diet-induced erectile dysfunction (ED) rats. Berberine may improve erectile function in rats with high-fat diet-induced erectile dysfunction and promote the growth of corpus cavernosum smooth muscle cells through the miR-342-3p/vascular endothelial growth factor A axis, providing a new idea for the treatment of hyperlipidemia-associated erectile function.