Therapeutic Effects of <i>Phyllanthus urinaria L</i> on Cisplatin‐Induced Acute Kidney Injury: Anti‐Inflammatory, Anti‐Apoptotic, and Anti‐Oxidative Action

Acute kidney injury (AKI) is a prevalent and serious clinical challenge with limited specific treatments. <i>Phyllanthus urinaria L</i> (<i>PU</i>), a well-regarded herbal medicine, possesses noted anti-inflammatory, antiviral, and antitumor properties. Yet, research into its renal protective effects, particularly for cisplatin-induced AKI, is markedly limited. Our study explores the therapeutic potential of <i>PU</i> against AKI triggered by cisplatin administration. Utilizing an AKI model induced by a substantial dose of cisplatin, we assessed renal function through histological examination (hematoxylin and eosin staining) and biochemical markers, including blood urea nitrogen (BUN) and serum creatinine (Scr). Our results demonstrated that <i>PU</i> may mitigate cisplatin's structural damage to renal tissue. Post-treatment with <i>PU</i>, a significant reduction in pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) was observed through quantitative polymerase chain reaction (PCR) analysis. Additionally, the expressions of apoptotic and anti-apoptotic proteins B cell leukemia/lymphoma two (Bcl-2), Bcl2-Associated X protein (Bax), and cleaved-caspase3 evaluated via Western blot and immunofluorescence indicated that <i>PU</i> could inhibit apoptosis in response to cisplatin injury. Oxidative stress markers, such as malondialdehyde (MDA) and superoxide dismutase (SOD), showed decreased MDA levels and elevated SOD activity following <i>PU</i> treatment, suggesting a reduction in oxidative damage. Furthermore, cisplatin-induced downregulation of <i>NRF2</i> and <i>NQO1</i> was countered by <i>PU</i>, highlighting its restorative effect on antioxidant pathways as confirmed by Western blot and immunofluorescence. Collectively, our findings endorse <i>PU</i>'s protective capability against cisplatin-induced AKI, endorsing its therapeutic potential to counteract cisplatin's nephrotoxicity.