Ameliorative Effects of Ethyl-Acetate Extract of Bidens pilosa on Oxidative Stress and Reproductive Impairment in Bisphenol A-Exposed Male Mice: Insight from In-silico, Invitro and In-vivo Studies.

Background: Bisphenol A (BPA), a ubiquitous environmental pollutant, is known to induce oxidative stress and disrupt male reproductive function. This study evaluated the ameliorative effects of the ethyl-acetate extract of Bidens pilosa L., Asteraceae (EABP) on oxidative stress and reproductive impairment in BPA-exposed male mice. Method: GC-MS phytocompounds from EABP were subjected to in-silico pharmacokinetic, drug-likeness, and toxicological screening using the SwissAdme and PkCSM web servers. Antioxidant capacity of EABP was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Over a 28-day period, male mice were assigned to six groups. The control group (Group 1) received distilled water, while Group 2 administered BPA at a dose of 100 mg/kg/day. Groups 3, 4, and 5 were treated with BPA in combination with EABP at doses of 250, 500, and 1000 mg/kg/day, respectively. Group 6 received BPA along with vitamin C at 100 mg/kg/day. Various parameters, including body weight, malondialdehyde, catalase, and superoxide dismutase level were assessed. Result: Molecular docking analysis revealed that 9,12,15-octadecatrienoic acid, a key phytoconstituent of EABP, exhibited strong binding affinity for both the androgen receptor (AR) and nuclear factor erythroid 2-related factor 2 (NRF2). Its interaction with AR was comparable to that of testosterone, suggesting potential androgenic activity, while its binding to NRF2 mirrored that of vitamin C. The extract's antioxidant activity was further supported by the DPPH radical scavenging assay, where it demonstrated moderate potency with an IC₅₀ of 6.11μg/mL, compared to 1.25μg/mL for vitamin C. in vivo findings showed that treatment with EABP at 250 mg/kg, 500 mg/kg, and 1000 mg/kg restored SOD activity and significantly reduced MDA levels. Catalase (CAT) activity also improved, particularly at the higher dose. Conclusion: Collectively, these results indicate that the EABP offers protective effects against BPA-induced oxidative stress, metabolic disturbance, and reproductive dysfunction, possibly through its combined antioxidant and hormone-like properties.