Exploring the role of <i>Withania somnifera</i> in male reproductive health: Insights from laboratory and clinical study

Various therapy options are evolving globally to address male reproductive dysfunction resulting from hormone imbalances, altered neuroendocrine interactions, infections, lifestyle changes, etc. Modern therapies, including hormonal therapy and assisted reproductive technologies, are expensive and have meager success rates (up to 30%) with side effects; yet, herbal medicines are recognized as an alternative therapeutic approach for male reproductive dysfunctions. The positive benefits of oral consumption of the roots of the perennial herb Withania somnifera (WS) (Ashwagandha) on the semen quantity and quality of reproductively challenged men have been previously investigated. The oral consumption of Ashwagandha roots has been shown to enhance sperm motility and numbers, impede lipid peroxidation, elevate antioxidant enzymes, and modulate the reproductive axis (hypothalamic–pituitary–testicular axes). The exact molecular cross-talk behind these actions remains elusive. This review examined the role of natural medicines on male reproductive health, offering a comprehensive analysis of various clinical and laboratory studies pertaining to WS. It showed a direct oxido-inflammatory-apoptotic mechanism that alleviates oxidative damages, apoptosis, and inflammation, alongside an indirect mechanism involving a dopaminergic-gamma-aminobutyric acid (GABAergic)-cholinergic secretion-associated as well as through hypothalamic–pituitary–gonadal-hypothalamic–pituitary–adrenal axes pathway that enhances hormonal equilibrium through interactions among endocrine glands to enhance male sexual function and fertility. In addition, it addressed how WS ameliorates various risk factor-associated reproductive dysfunctions and enhances overall male reproductive health.