Hepatoprotective Potentials of Pleurotus pulmonarius against Cadmium and Restraint Stressinduced Liver Injury: Integrated in vivo and in silico Evidence

Abstract

The present investigation was carried out to evaluate the hepatoprotective activity of aqueous ethanolic extract of Pleurotus pulmonarius (AEEPP) against combined cadmium and restraint stress induced hepatotoxicity in rats. Preliminary mycochemical screening indicated the presence of phenolics, flavonoids and polysaccharides. AEEPP showed concentration dependent DPPH and nitric oxide radical scavenging properties with IC50 values of 16 and 55 μg/mL respectively. The disaccharide (HEX-HEX) demonstrated the most encouraging results in silico molecular docking, with a docking score of −11.109 kcal/mol and MMGBSA energy of −63.72 kcal/mol, indicating its possible interaction with the Keap1–Nrf2 pathway. Cadmium and constraint stress dramatically enhanced hepatic enzymes and oxidative stress, and depressed antioxidant defense in vivo. Treatment of AEEPP especially at 300 mg/kg dramatically restored the levels of SOD, CAT, GSH, GPx and improved the serum biochemical markers (p<0.0001). Liver morphology and histopathology revealed reduced inflammation, degradation of hepatocytes and tissue injury with near normal architecture at 300 mg/kg. Behavioral tests (OFT and rotarod) were considered supportive because no significant treatment-related changes were observed. To summarize, AEEPP showed hepatoprotective effect on cadmium and restraint stress produced liver injury perhaps due to its antioxidant and bioactive ingredients. Major Findings: The phenolics, flavonoids and polysaccharides included in AEEPP demonstrated excellent radicalscavenging activity. HEX-HEX exhibited favorable Keap1–Nrf2-related docking. AEEPP at 300 mg/kg increased antioxidant and liver-function measures and greatly conserved the hepatic architecture. Behaviors: No significant treatment-related changes in behavior were observed.