ABSTRACT
Sexuality is a major fundamental principle of reproduction involving conjugation, conception and procreation. Despite the increase in the use of some of the conventional aphrodisiacs for sexual dysfunction, medicinal plants have undoubtedly continued to gain attention as an alternative for the improvement or enhancement of sexual life. This study aimed to investigate the ethnomedicinal claim of usage of Annona senegalensis in treatment of male sexual dysfunction using in vivo and in vitro models. The methanol extracts of A. senegalensis root (ASRB), stem (ASSB) and leaves (ASL) were screened for phytochemical constituents. In vivo aphrodisiac activity study and in vitro anti-lipid peroxidation potentials (thiobarturic acid reactive substances assay) of the extracts and the fractions of ASRB were investigated. Acute and subacute toxicity studies of ASRB were carried out. Male albino rats were administered with graded doses of the extracts of A. senegalensis (50, 100 and 200 mg/kg) and ASRB fractions (25, 50 and 100 mg/kg), their sexual behaviour parameters and serum testosterone, LH, FSH, serum and testicular cholesterol concentrations were evaluated at days 1, 3 and 5. Sildenafil was used as the positive control drug. Bioactivityguided isolation of aphrodisiac principle from ASRB was carried out using combination of different chromatographic techniques. The isolated compound was subjected to spectroscopic analysis for characterisation. In silico molecular docking analysis of the isolated compound was carried using PyRx software and Biovia Discovery Studio. Presence of tannins, saponins, flavonoids, reducing sugars, terpenoids and steroids were detected in the three extracts. Different doses of A. senegalensis crude extracts significantly (P<0.05) increased mount frequency (MF) and intromission frequency (IF), decreased ejaculatory frequency (EF), mount latency (ML), intromission latency (IL), post-ejaculatory interval (PEI) and prolonged ejaculatory latency (EL) in non-dose-dependent manner when compared with the negative control. Serum testosterone, FSH, LH, serum and testicular cholesterol levels were also significantly increased (P<0.05) by different doses of the crude extracts when compared with the controls. ASRB and ASSB (20 – 100 μg/mL) produced 68.66% and 45.3% inhibition of lipid peroxidation respectively as well as the aqueous fraction of ASRB (58.14%). Aqueous and ethyl acetate fractions of ASRB at 50 and 100 mg/kg significantly (P<0.05) increased MF, IF, decreased ML, IL and prolonged EL. These fractions also produced significant increase (P<0.05) in serum testosterone, LH, FSH and serum cholesterol levels of male albino rats when compared with the negative control. The most active fraction (aqueous) of ASRB yielded betulinic acid which exhibited PDE5 inhibition through hydrogen bonding and hydrophobic interactions in in silico molecular analysis.. This study experimentally justified the ethnomedicinal claim of the use of A. senegalensis in the treatment of male sexual dysfunction. Betulinic acid was isolated from A. senegalensis root bark and was linked to its aphrodisiac potentials.