Ethno-pharmacological relevanceAnthonotha macrophylla, a plant with extensive ethnomedicinal uses, has various parts attributed to healing properties. The bark is claimed to be used to treat venereal diseases while the roots are used to treat intestinal discomfort. Gum extract from the bark provides pain relief, while the leaves are used for treating gonorrhoea, diarrhoea, and malaria. Additionally, the leaves are believed to enhance sexual behaviour. Although the age-long folkloric use of Anthonotha macrophylla leaf as aphrodisiac in female rats was substantiated with scientific evidence, the study did not account for the aphrodisiac activity in paroxetine-induced sexual dysfunction in male rat model. Aim of the studyThis study investigated the aphrodisiac activity of aqueous extract of Anthonotha macrophylla leaves (AEAML) in paroxetine-induced sexual dysfunction male rats (PISDMR). Materials and methodsForty-two male rats (144.86 ± 1.21 g) were assigned into six groups (A-F). Group A received distilled water only, while PISDMR in Groups B, C, D, E and F received distilled water, 7.14 mg/kg body weight of sildenafil citrate (reference drug), 25, 50 and 100 mg/kg body weight of AEAML once daily for 7 days. Data were analyzed using a one-way Analysis of Variance (ANOVA) and Tukey's post-hoc test at a 5% level of significance after the determination of male sexual behaviour parameters and associated biochemical indices. ResultsAEAML contained 8 mineral elements and 14 amino acids; potassium (368.24 mg/100g) and glycine (352.70 mg/100g) were the most abundant while cadmium (0.01 mg/100g) and histidine (0.70 mg/100g) were the least. Administration of paroxetine prolonged/increased (p < 0.05) the mount latency (ML), intromission latency (IL), ejaculation latency (EL), post-ejaculatory interval (PEI), and lowered/reduced (p < 0.05) the mount frequency (MF), intromission frequency (IF) and ejaculation frequency (EF). Paroxetine also decreased the weight of the caudal epididymis, seminal vesicle, ventral prostate, and testis, levels of dihydrotestosterone (DHT), testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), dopamine, acetylcholine (ACH), nitric oxide (NO), cyclic guanosine monophosphate (cGMP) and increased the levels of serotonin, γ-aminobutyric acid (GABA), phosphodiesterase V (PDE V) and acetylcholinesterase (AChE) of the animals. In contrast, AEAML significantly (p < 0.05) lowered/reduced the paroxetine-induced related increases in the ML, IL, EL, PEI, and prolonged/increased (p < 0.05) the paroxetine-induced related decreases in the MF, IF and EF. The AEAML also reversed (p < 0.05) the paroxetine-induced related decreases in the weight of the caudal epididymis, seminal vesicle, ventral prostate, testis, levels of DHT, testosterone, LH, FSH, dopamine, ACH, NO, cGMP and the paroxetine-induced related increases in the levels of serotonin, GABA, PDE V and AChE. ConclusionAEAML contains aphrodisiac bioactive agents that can be explored as drug lead for MSD.