Longevity Spinach (Gynura procumbens) Ameliorated Oxidative Stress and Inflammatory Mediators in Cisplatin-Induced Organ Dysfunction in Rats: Comprehensive in vivo and in silico Studies.

Abstract

This study focused to assess the efficacy of Gynura procumbens (GP) leaf extract against cisplatin (CP)-induced hepatorenal complications in Wister albino rats. Additionally, it aims to detect polyphenolic compounds using high-performance liquid chromatography with diode-array detection (HPLC-DAD). The rats were treated intraperitoneally with CP (7.5 mg/kg) to mediate hepatorenal damage. They were then treated with GP extract (75 and 150 mg/kg, P.O.) for 7 consecutive days. Although GP extract significantly ameliorated CP-mediated hepatorenal biomarkers like alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) levels in a dose-dependent manner, GP extract at 150 mg/kg dose normalized hepatorenal biomarkers ALP (45.11 U/L), ALT (34 U/L), AST (29 U/L), creatinine (10.3 mg/dl) and BUN (11.19 mg/dl) while comparing to control and disease group. Similarly, though it significantly reduced CP-induced oxidative stress inducers, including nitric oxide (NO) and advanced oxidative protein products (AOPP), higher dose (150 mg/kg) exhibited better activity in reducing NO (281.54 mmol/gm tissue in liver and 52.73 mmol/gm tissue in the kidney) and AOPP (770.95 mmol/mg protein in liver and 651.90 mmol/mg protein in the kidney). Besides, it showed better enhancement in the antioxidant enzymes superoxide dismutase, and glutathione levels at a higher dose (150 mg/kg). Histopathological studies showed that CP caused collagen accumulation in the liver and kidney tissues. GP extract drained the collagen mass and acted against hepatorenal damage. Ellagic acid, gallic acid, quercetin hydrate, kaempferol, and rutin hydrate were revealed in GP extract. In-silico modelling showed good docking scores of the polyphenolic compounds with molecular targets including CYP4502E1, NF-κB, caspase-3, and TNF-α. GP could be an effective therapeutic option for management of anticancer drugs' complications like CP-induced organ damage, although clinical studies are required to establish herbal formulation.