Protective effects of hydroethanolic extract of Mentha longifolia L. leaves against hepato-renal toxicity induced by furan exposure: In vivo and In silico studies

Furan is a potential human carcinogen that forms in certain processed foods at trace levels, typically in the nanogram per gram range. The present study aimed to explore the antioxidant and hepatorenal protective effects of a chemically characterized extract from Mentha longifolia (ML-extract) against furan-induced hepatorenal damage in rats. To determine the phenolic profile of ML extract, HPLC-DAD analysis was performed, and its antioxidant capacity was evaluated using the DPPH, ABTS, TAC, and RP assays. Twenty-four normal Wistar rats were divided into four experimental groups: a control group that received distilled water orally (10 mL/kg BW), a group treated exclusively with ML-extract (200 mg/kg BW), a group exposed only to furan (40 mg/kg/day BW), and a group exposed to furan while simultaneously receiving ML-extract. Serum samples were collected to measure renal biomarkers (urea, creatinine, and total protein) and hepatic biochemical parameters (ASAT, ALAT, ALP, and total bilirubin). Lipid markers such as triglycerides and total cholesterol were also assessed. Additionally, fresh organ samples were collected for histopathological analysis. Furthermore, molecular docking was performed using the major compounds in ML-extract to investigate their interactions with target proteins. The in vitro analyses demonstrated that the tested extract exhibited strong antioxidant activity, which correlated with its rich composition of phenolic compounds, particularly caffeic acid, ferulic acid, naringin, and rutin. Likewise, in vivo studies revealed that treatment with ML-extract, either alone or in combination with furan, effectively alleviated biochemical parameters. These included a significant increase in kidney biomarkers (total bilirubin and urea levels), hepatic enzyme levels (ALT, AST, ALP, and total protein), and disruptions in lipid profile (triglycerides and total cholesterol) compared to the control group. Furthermore, the extract contributed to the preservation of hepatic and renal functions, reinforcing its potential protective effects against furan-induced toxicity. Molecular docking analysis further demonstrated that bioactive compounds, such as 4-Hydroxybenzoic acid, ferulic acid, caffeic acid, sinapinic acid, hesperidin, rutin, naringin, and cinnamic acid, exhibited strong binding affinity in complex with hepatoprotective protein (3ANS) and antioxidant (5IKQ) proteins, supporting the experimental findings. In summary, these results suggest that the hydroethanolic extract of M. longifolia may serve as a potential therapeutic agent for preventing liver and kidney damage resulting from xenobiotic exposure.