Anti-androgenic and anti-proliferative properties of methanolic leaf extract of Allamanda cathartica Linn. in adult mouse testis: Evidences from in vivo and in silico studies

Dysregulation in androgen production causes a variety of clinical disorders like male pattern baldness, hirsutism, acne vulgaris, benign prostatic hyperplasia, prostate cancer and polycystic ovarian syndrome. Although the common synthetic drugs used to treat these diseases have many side effects, there is growing demand for alternative and herbal therapies. Allamanda cathartica Linn. (family, Apocynaceae) is traditionally used to treat variety of diseases because of its hepatoprotective, antidiabetic, anti-inflammatory, antitumor and antimicrobial properties. However, the effects of Allamanda leaves on testosterone production still remain elusive. The present study aims to elucidate the effect and possible mode(s) of action of the methanolic leaf extract of A. cathartica (MLEAC) on androgen biosynthesis and germ cell proliferation in adult mouse testis. Adult male C57BL/6J mice were orally administered MLEAC (150 and 300 mg/kg body weight/day) or distilled water (controls) for 42 days. MLEAC treatment caused non-uniform degenerative changes in the histoarchitecture of testis. The treatment also had negative impact on serum testosterone level with downregulation of the expressions of major steroidogenic proteins (StAR, CYP11A1, 3β-and 17β-HSD3). Flow cytometry and immunohistochemical analyses showed impaired gem cell proliferation in MLEAC-treated mice testes. The GC-MS method identified 20 phytocompounds in MLEAC. The in silico study further revealed that GC-MS-derived phytochemicals have the potential to bind with major steroidogenic proteins in testis. MLEAC treatment thus causes suppression of germ cell proliferation via downregulation of testosterone production. Keeping in view the traditional use of Allamanda, the present findings may prove helpful in the search of a plant-based anti-androgenic compound.