Myricetin-mediated Ameliorative Effect of a Super-critical Fluid Extract of Myrica esculenta Against Cyclophosphamide-induced Oligospermia in Sprague Dawley Rats

Background: Oligospermia contributes to male infertility through oxidative stress, impairment of spermatogenesis and disruption of steroidogenic function. Myrica esculenta is a medicinal plant reported to exhibit anti-oxidant and anti-inflammatory activities. Aim: To evaluate the protective effect of Supercritical fluid Extract of M. esculenta (SEME) against cyclophosphamide-induced oligospermia. Methods: The SEME was prepared and GC-MS profiling was conducted to confirm the presence of myricetin in SEME. Subsequently, thirty-six Sprague Dawley rats were assigned to six groups. Except for the normal control group, all animals were administered cyclophosphamide (30 mg/kg; intraperitoneally) once daily for five consecutive days to induce oligospermia. SEME was administered orally to three groups at doses of 100, 200, and 300 mg/kg, respectively, for 15 days. Sexual behaviour parameters, including Mount Latency (ML) and Frequency (MF), Intromission Latency (IL) and Frequency (IF), Ejaculation Frequency (EF), Hesitation Time (HT), PostEjaculatory Latency (PEL), and Penile Erection Index (PEI) were recorded. On Day 15, testicular index and Blood Glucose Levels (BGLs) were measured. Subsequently, sperm parameters (count, motility, viability, and morphology), oxidative stress markers (glutathione and catalase), and serum biochemical indices (testosterone, 3β-hydroxysteroid dehydrogenase [3β-HSD], and 17β-HSD) were assessed. Results: Treatment with SEME significantly reduced ML (P < 0.05), IL (P < 0.05), HT (P < 0.05), and PEL (P < 0.05), while increasing IF, EF, MF, and PEI (P < 0.05). SEME treatment restored testicular index and significantly reduced elevated BGLs (P < 0.05). It also improved sperm count, motility, viability, and morphology (P < 0.05), elevated glutathione and catalase levels (P < 0.05), and regulated testosterone, 3β-HSD, and 17β-HSD levels (P < 0.05). Conclusion: SEME demonstrated a protective role against cyclophosphamide-induced oligospermia through mitigation of oxidative stress restoration of spermatogenic and steroidogenic functions. Major Findings: Treatment with SEME exhibited protective effect against cyclophosphamide-induced oligospermia through improving sexual behaviour, sperm parameters, and testicular index. This protective effect was associated with reduction of oxidative stress parameters and regulation of steroidogenic enzymes.