Mucuna pruriens var. pruriens Ethanolic Seed Extract Enhances Erectile Function-Related Mechanisms: Integrated In Vitro and In Vivo Evidence

Mucuna pruriens (Linn.) DC. var. pruriens is used as a traditional medication to enhance male sexual function, yet integrated evidence linking vascular-cell mechanisms to in vivo efficacy and safety of a standardized extract remains limited. This study evaluated the ethanolic seed extract of M. pruriens var. pruriens (MPSE) on erectile function-related mechanisms, addressing the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP)–phosphodiesterase type 5 (PDE5) pathway in vitro, together with mounting frequency, anxiety-like behavior, locomotor activity, and cardiovascular safety in vivo. Soxhlet extraction with 80% ethanol yielded a dark brown, syrupy extract (12.28% w/w), which was standardized by high-performance thin-layer chromatography to contain 278 mg/g extract (27.8% w/w) of L-DOPA (Rf 0.38). Mechanistic effects were assessed in human umbilical vein endothelial cells (HUVECs), pulmonary artery smooth muscle cells (PASMCs), and a PDE5A1 enzyme assay. Male Wistar rats received MPSE (50, 100, and 200 mg/kg) orally for 15 days, with hemodynamic assessment in normotensive and Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. MPSE significantly increased eNOS expression and NO production in HUVECs, elevated intracellular cGMP in PASMCs, and directly inhibited PDE5A1 enzymatic activity. Repeated administration significantly increased mounting frequency relative to baseline without altering serum testosterone levels, anxiety-like behavior, locomotor activity, mean arterial pressure, or heart rate. These findings indicate that MPSE modulates erectile function-related mechanisms, primarily through peripheral vascular effects on the NO–cGMP–PDE5 pathway, and suggest a favorable safety profile. Erectile function itself was not directly assessed and warrants confirmation in models of erectile response. MPSE nevertheless represents a promising plant-derived candidate for erectile dysfunction.