Withania somnifera ameliorates sexual arousal and impotence in stressed sexually sluggish male rats by modulating neurotransmitters and NO/cGMP/PDE5α pathway

Abstract

Ethnopharmacological relevance: Psychological stress is a growing global threat to male sexual potency and erection efficiency. Withania somnifera (L.) Dunal (WS), also known as Ashwagandha, is a well-known Ayurvedic herb. The roots of Withania somnifera improve the body's ability to handle stress, strengthen the immune system, promote healthy ageing, and have aphrodisiac properties with male sexual stimulation effects. Despite its widespread acceptance as an Ayurvedic stress-relieving drug with beneficial effects on male reproductive health, Withania somnifera has yet to be studied for its potential role in improving the sexual arousal and erectile dysfunction of psychologically stressed sexually sluggish males.

Aim of the study: To investigate the therapeutic effects of purified root powder of Withania somnifera on sexual behaviour and erectile efficiency in stressed sexually sluggish male rats.

Materials and methods: Sexually sluggish male rats were screened by premating tests after being exposed to a psychological stressor, restraint stress, 3 h/day for 30 days. Subsequently, these rats were treated with purified root powder of WS (150 or 300 mg/kg/day-PO) or sildenafil (5 mg/kg/day-PO) for 30 days. The rats were sacrificed after 24 h of the last treatment, and the effects on various factors related to sexual behaviour, penile histomorphology, serum hormones, and neurotransmitters associated with sexual arousal and penile erection were examined.

Results: WS treatment improves prosexual and sexual behaviour in psychologically stressed sexually sluggish male rats by increasing non-contact erections and mounts, intromission, and ejaculation frequencies, while decreasing sexual exhaustion by decreasing post-ejaculation intervals and latencies. WS also modulates neurotransmitters and hormones associated with sexual desire and stress, including dopamine, serotonin, corticosterone, and prolactin. Additionally, there was also a dose-dependent increase in serum LH, FSH, and testosterone levels. The administration of WS to sexually sluggish rats resulted in significant improvements in penile histomorphology, specifically by increasing the ratio of smooth muscle (SM) to collagen. Furthermore, in sexually sluggish rats, WS treatment increased the expression of markers associated with penile erection facilitation, such as nNOS, eNOS, p-Akt, nitric oxide, acetylcholine, and cGMP. Notably, WS treatment decreased the expression of penile PDE5α in these rats in a dose-dependent manner. Remarkably, the therapeutic effects of WS are comparable to those of sildenafil.

Conclusions: Purified root powder of Withania somnifera was found to improve sexual arousal and erection efficiency in stressed, sexually sluggish male rats. This improvement was achieved by modulating the HPG and HPA axes as well as the NO/cGMP/PDE5α pathway involved in penile erection. Thus, our findings strongly support the potent therapeutic potential of purified root powder of WS in improving the sexual health of stressed sexually sluggish rats.

Keywords: Erectile dysfunction; Neurotransmitters; Psychological stress; Sexual behaviour; Withania somnifera.