Molecular and In-Silico insights into eremomastax speciosa protection against cadmium toxicity

• Eremomastax speciosa ( E. speciosa) extract significantly altered steroidogenic enzyme levels, suggesting a potential protective mechanism. • E. speciosa extract improved several biochemical parameters, indicating its role in mitigating cadmium toxicity. • Rats treated with extract of E. speciosa showed improved reproductive health markers, highlighting the extract's potential as a therapy for cadmium-induced reproductive damage. Cadmium (Cd) exposure is a major environmental concern that disrupts reproductive physiology through oxidative stress, inflammation, and impaired steroidogenesis. This study investigated the protective mechanisms of Eremomastax speciosa ethanol extract against Cd-induced ovarian toxicity in female rats, integrating phytochemical, biochemical, molecular docking, gene expression, and histopathological analyses. Thirty-five rats were assigned to five groups (n = 7) and exposed to CdCl₂ (5 mg/kg b.w.) for 60 days, followed by 28 days of oral treatment with distilled water, Clomid (0.5 mg/kg), or E. speciosa extract (200 and 400 mg/kg). GC–MS analysis identified 78 bioactive compounds, with hexadecanoic acid, caryophyllene, linoleic acid, kaempferol, and piperine showing strong binding affinities to aromatase and 17β-hydroxysteroid dehydrogenase, suggesting potential aromatase inhibition. Cd exposure caused oxidative stress, elevated inflammatory cytokines, lipid dysregulation, and downregulation of steroidogenic genes ( Star, Hsd3b2, Hsd17b1, Cyp19a1 ). Treatment with E. speciosa restored antioxidant enzyme activities (SOD, CAT), normalised estradiol and testosterone levels, and upregulated steroidogenic gene expression. Histopathological findings revealed dose-dependent ovarian regeneration with developing follicles and restored corpora lutea, particularly at 400 mg/kg. This study provides new molecular and mechanistic evidence of E. speciosa as a multi-target phytotherapeutic agent capable of modulating oxidative stress, inflammation, and steroidogenic pathways disrupted by Cd toxicity. These findings advance understanding of African medicinal plants’ reproductive protective mechanisms and position E. speciosa as a promising natural model for developing interventions against heavy metal-induced infertility