GC/MS and LC–ESI–MS/MS Analysis of <i>Cucurbita pepo</i> L. Aerial Parts Methanolic Extract via Regulating Oxidative Stress and Inflammatory Mediators Against Acrylamide‐Induced Nephrotoxicity in Rats Supported by In Silico Investigations

Acrylamide (ACR) is a hazardous chemical pollutant due to thermal processing of certain foods. This study aimed to profile the metabolites of the methanolic extract of Cucurbita pepo L. (Cucurbitaceae) aerial parts against nephrotoxicity induced by ACR in rats. GC/MS and LC-ESI-MS/MS analysis were used for isolation and differentiation of different metabolites. In silico study was done on the identified triterpenes and sterols. In vivo nephrotoxicity was done by intraperitoneal injection of ACR to rats. Serum kidney function tests, oxidative stress, inflammatory markers, and histopathological observation were evaluated. Twenty-four compounds were identified, where stigmasterol and β-sitosterol were the most prevalent metabolites. Fifty-one compounds in positive and negative modes were also identified. Four compounds were isolated: stigmasterol, β-sitosterol, p-coumaric, and p-hydroxybenzoic. Cucurbitacin A 2-O-β-d-glucopyranoside and karaviloside XIII possessed anti-inflammatory and antioxidant effects by in silico study. Treatment with C. pepo L. aerial parts methanolic extract restored the levels of creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), and glutathione (GSH). In conclusion, C. pepo L. leaves methanolic extract possessed curative effect against ACR toxicity due to its richness with different bioactive compounds.