Berberine (BER) is a potent antioxidant and anti-inflammatory compound with several health benefits. We investigated the impact of sub-chronic BER supplementation on male rat reproductive function from the prepubescence to adulthood. Wistar rat pups (PND 21) were divided into five groups (n = 10 pups/group). The control animals received distilled water (2 mL/kg, p.o), and the treated groups received different doses of BER: 25, 50, 100, and 200 mg/kg body weight, p.o) from PND 28 to PND 68. Using biochemical, histomorphological, and pathology methods, we examined the reproductive function of the treated rats. Compared to the control, prepubertal BER supplementation showed no significant effect on body/organ weight. Graded doses of BER supplementation improved (p < 0.05) reproductive hormone levels (FSH, luteinising, prolactin and testosterone), testicular enzyme activities (alkaline phosphatase, acid phosphatase, lactate dehydrogenase), and sperm functional parameters. Also, BER supplementation increased antioxidant enzyme activities and total thiol levels, decreased (p < 0.05) reactive oxygen and nitrogen species, lipid peroxidation and protein carbonyl, nitric oxide, tumour necrosis factor-alpha (TNF-α) levels, and myeloperoxidase activity in rat’s hypothalamus, epididymis and testes. The histology of examined organs of rats treated with BER was comparable to the control, exhibiting abundant spermatozoa (epididymis and testes) and neuronal cells (hypothalamus). These findings suggest that BER supplementation substantially enhanced male rat reproductive function by lowering oxidative stress-related damage to cellular macromolecules, such as protein carbonylation and lipid peroxidation. Moreover, BER reduced pro-inflammatory stresses in the organs under investigation. We highlight the benefits of BER for supporting reproductive health, with potential therapeutic uses to relieve disorders of reproductive function. Nevertheless, additional research is required to clarify the molecular and functional test biomarkers that require BER to have effects that promote reproductive health.
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