Androgenic Efficacy and Mechanism of Glycosides-Based Standardized Fenugreek Seeds Extract Through Aromatase And 5-Alpha Reductase Inhibition

Introduction: Fenugreek seeds glycosides content have many health benefits. Objective: To evaluate the androgenic efficacy and probable mechanism of glycosides-based standardized fenugreek seed extract (SFSE-G) in laboratory rats. Methods: Male Wistar rats were administrated with 28-days of once-daily oral administration of SFSE-G (10 or 35 mg/kg) on sexual and orientational behavior with female rats, serum testosterone concentrations, weights of reproductive system-related organs (seminal vesicles, prostate, levator ani), nitric oxide level in penis homogenate, sperm count in the cauda epididymis, and testis histology were evaluated. Separate groups of rats with a positive control (testosterone propionate (10 mg/ kg, s.c. bi-weekly) and vehicle control (distilled water) were maintained. In addition, the safety of acute intravenous administration of SFSE-G (1 mg/kg) on cardiovascular function parameters was evaluated. Moreover, the inhibitory potential of SFSE-G against aromatase and 5-alpha-reductase enzymes was evaluated in vitro. Results: Subacute administration of SFSE-G (35 mg/kg, oral) to male rats showed androgenic efficacy in sexual behavior (increased mounting and intromission latency and rearing), with increased weights of seminal vehicles, prostate and levator ani muscles, serum testosterone levels, sperm count, and penile NO concentration, while preserving the normal architecture of the testes. Acute intravenous administration of SFSE-G to rats increased intracavernous pressure but retained normal cardiovascular parameters, such as blood pressure, heart rate, and corrected QT interval (QTc). SFSE-G showed significant inhibition of aromatase and 5-alpha-reductase in vitro. Conclusion: SFFE-G exhibited significant androgenic and spermatogenic efficacy, mediated through testosterone metabolism inhibition, without affecting the cardiovascular system in laboratory rats.