Evaluation of anti-gonadal activity of chloroform fraction of Thevetia peruviana leaves in male albino rats

Objective: Anti-gonadal activity of chloroform fraction of Thevetia peruviana leaves (Ch-TPHmLE) in male rat was evaluated in this study.Materials and Methods: The Ch-TPHmLE (۵ mg/۱۰۰ g of body-weight (BW)/day) and standard antiandrogenic agent cyproterone acetate (CyPA) at the dose of ۲.۵ mg/۱۰۰ g of BW were given to male rats for ۲۸ days. Sperm profile, serum gonadotrophins and testosterone were measured. Testicular superoxide-dismutase, catalase activities and zymographic-expression, malondialdehyde, conjugated-diene, TNF-α levels and immunohistochemical markers were evaluated. Testicular steroidogenic enzyme activities and androgen receptor (AR), StAR, HSD, Bcl۲, P۵۳, caspase-۳ and BAX gene expressions were observed. LC-MS study was done for Ch-TPHmLE.Results: Sperm profile, gonadotrophins, testosterone as well as testicular steroidogenic key enzyme activities were reduced significantly (p<۰.۰۵) and StAR, AR, HSD genes expressions were downregulated in Ch-TPHmLE and CyPA treated groups compared to the control group. Testicular anti-oxidant enzyme activities and zymographic-expression patterns were reduced significantly and malondialdehyde, conjugated-diene, TNF-α were increased significantly in the Ch-TPHmLE and CyPA treated groups. Testicular caspase-۳ gene and proapoptotic genes P۵۳, and BAX expressions were upregulated but anti-apoptotic gene Bcl۲ was downregulated as confirmed by elevated number of apoptotic germ cells in immunostaining. The bio-active phyto-compounds γ-Sitosterol, Stigmasterol, Dehydroergosterol, β-Amyrin, Lupeol, and α-Amyrone were identified by LC-MS analysis of Ch-TPHmLE.Conclusion: It is concluded that the synergistic action of these phyto-molecule(s) of chloroform fraction of Thevetia peruviana (TPHmLE) shows anti-gonadal activity by alteration of serum gonadotrophins, and androgen levels and generation of excess oxidative free-radicals that trigger testicular germ-cell apoptosis.

کلیدواژه ها:

Phyto molecules Sperm count Catalase ۱۷&beta ، HSD Androgen receptor Anti ، spermatogenic