Saffron extract alleviates D-gal-induced late-onset hypogonadism by activating the PI3K-Akt-Nrf2 signaling pathway

Late-onset hypogonadism (LOH) is a common age-related condition in men, characterized by a decline in serum testosterone and a range of associated signs and symptoms, and is classified as impotence in traditional medicine. Saffron is the dried stigma of Crocus sativus L., which is used in traditional medicine as an aphrodisiac.

This study aimed to investigate the effects of saffron extract (SE) on LOH using an aging mouse model and Leydig cells.

The potential mechanisms and therapeutic targets of SE for the treatment of LOH were first identified using network pharmacology. An aging model was induced in mice by administration of D-galactose, followed by treatment with varying concentrations of SE. Subsequent assessments of serum testosterone levels, semen quality, testicular aging, oxidative stress, and apoptotic markers were performed to assess the impact of SE and to elucidate its mechanisms. In addition, in vitro experiments assessed the effect of SE on Leydig cell viability, oxidative stress, and apoptosis.

The results showed that SE could modulate the PI3K-Akt-Nrf2 signaling pathway, enhancing Leydig cell resistance to oxidative stress and reducing Leydig cell apoptosis, thereby improving Leydig cell function and alleviating the decrease in serum testosterone associated with aging.

Saffron is a promising strategy for the treatment of LOH and provides an effective approach to alleviate serum testosterone decline in older men.