Metabolic-endocrine remodelling of the testis under polystyrene nanoplastic exposure: Intervention by organ-specific phytocomplexes of Nelumbo nucifera.

Polystyrene nanoplastics (PS-NPs) are emerging endocrine-disrupting pollutants that can accumulate systemically and impair male reproduction by inducing oxidative stress, hormonal dysregulation, and disrupted spermatogenesis. Nelumbo nucifera (lotus) is a medicinal aquatic plant rich in polyphenols and flavonoids with antioxidant and anti-inflammatory properties. This study evaluated the protective effects of N. nucifera leaf, flower, and rhizome extracts against PS-NP-induced testicular dysfunction in Rattus norvegicus. Male rats were orally exposed to PS-NPs (200 µg/kg bw) and co-treated with N. nucifera extracts (200 mg/kg bw) for 55 days, quercetin an effective free-radical scavenger and anti-inflammatory, was utilized as a reference. PS-NP exposure resulted in testicular accumulation and pronounced oxidative and inflammatory injury, evidenced by increased malondialdehyde (MDA) and elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) alongside reduced antioxidant enzyme activities (SOD, CAT). PS-NPs also perturbed testicular energy metabolism (GLUT1, HK1, PKM, GYS1, GLUT8), suppressed steroidogenic genes (HSD3β, HSD17β), reduced serum luteinizing hormone (LH), and impaired sperm quality. Co-treatment with N. nucifera extracts mitigated these alterations, with the rhizome extract demonstrating the most significant enhancement. This tendency aligned with the rhizome's elevated total phenolic content and ABTS radical-scavenging activity, corresponding with a reduced testicular PS-NP accumulation. Molecular docking further supported mechanistic relevance, showing high predicted affinities of lanosterol and cycloartenol toward SOD, CAT, LH receptor (LHR), and androgen receptors. These findings demonstrate that N. nucifera, especially the rhizome exerts potent antioxidant, anti-inflammatory, and endocrine-restorative effects against nanoplastic-induced testicular toxicity, highlighting its potential as a multitarget phytotherapeutic agent.