Methotrexate (MTX) is a widely administered drug to treat inflammatory, and autoimmune diseases and malignant tumors. Sadly, its use harms several organs, including kidney impairment. This study aimed to determine if the ethanolic extract of Paeonia officinalis (P. officinalis) roots might protect the kidneys from the damage caused by MTX. GC-MS technique investigated the analysis of active constituents of P. officinalis root extract. Rats were administered P. officinalis extract (200 mg/kg/day orally) with or without MTX (20 mg/kg once i.p. at day 9) for 14 days. GC-MS study of P. officinalis roots extract revealed the presence of 17 phytochemical substances, including octacosane, retinol acetate, nonacosane, tricin methyl ether, casticin, and (-)-catechin gallate. Increases in blood urea and creatinine as well as several pathological abnormalities in renal tissue and tubules, were all generated by MTX when compared to the control, indicating nephrotoxic effects. The oxidative stress brought on by MTX has been demonstrated as a decrease in renal superoxide dismutase (SOD) activity and an increase in malondialdehyde (MDA) content. By increasing renal interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-α), MTX also caused renal inflammation. Pretreatment of MTX-injected rats with P. officinalis root extract improved all oxidative and inflammatory indicators examined as well as kidney functional and structural indices. The current study first demonstrates the protective effect of P. officinalis root extract against MTX-induced kidney damage in rats. It may be due to its antioxidant and anti-inflammatory active components.
