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Abstract Background During the last few decades, patients worldwide have been interested in using alternative medicine in treating diseases to avoid the increased side effects of chemical medications. Green coffee is unroasted coffee seeds that have higher amounts of chlorogenic acid compared to roasted coffee. Green coffee was successfully used to protect against obesity, Alzheimer disease, high blood pressure and bacterial infection. Methods This study aimed to investigate the probable protective activity of the green coffee methanolic extract, silymarin and their combination on CCl4-induced liver toxicity in male rats. Thirty Sprague – Dawley male albino rats were divided into 5 groups; control negative (G1) just got the vehicle (olive oil) and the other four groups received CCl4 dissolved in olive oil through an intraperitoneal injection and were divided into untreated control positive group (G2), the third group (G3) was treated with green coffee methanolic extract, the fourth group (G4) was treated with silymarin, and the fifth group (G5) was treated with a combination of green coffee methanolic extract and silymarin. Results In the positive control group treated with CCl4 (G2), the CCl4-induced toxicity increased lipid peroxidation, IL-6, kidney function parameters, liver function enzymes, total cholesterol, triglycerides and low-density lipoproteins, and decreased irisin, antioxidants, CYP450 and high-density lipoprotein levels. Hepatic tissues were also injured. However, treating the injured rats in G3, G4 and G5 significantly improved the altered parameters and hepatic tissues. Conclusions Green coffee methanolic extract, silymarin, and their combination succeeded in protecting the male rats against CCl4 hepatotoxicity due to their antioxidant activity. Effect of green coffee methanolic extract mixed with silymarin in G5 was more efficient than that of green coffee methanolic extract in G3 or silymarin in G4.

In the current study, the hepatoprotective activity of vanillic acid, silymarin, and vanillic acid-loaded silver nanoparticles (AgNPs) against CCl4-induced hepatotoxicity was tested in male rats for four weeks. Thirty male rats were divided into five groups (n = 6). The 1st group was a negative control, the 2nd group was a positive control, the 3rd group was treated with 100 mg/kg b.w. of vanillic acid, the 4th group was treated with 100 mg/kg b.w. of vanillic acid–AgNPs, and the 5th group was treated with 50 mg/kg b.w. of silymarin. The CCl4-induced hepatic toxicity in the 2nd group was revealed by the liver function and all other biochemical tests. Liver enzymes, bilirubin, lipid peroxidation, lactate dehydrogenase, and interleukin-6 were elevated, whereas, total protein, antioxidant enzymes, and irisin were decreased compared to the negative control. The hepatic tissues were also injured as a result of the CCl4-induced hepatotoxicity. Treating the hepatotoxic rats with vanillic acid moderately protected the rats of the 3rd group, whereas treatment with vanillic AgNPs and silymarin in G4 and G5, respectively, greatly protected the rats against the CCl4 hepatotoxicity, approaching the normal biochemical levels and liver tissue appearance. The biochemical tests were confirmed by the histological investigations of liver tissue.