Acute Toxicity and Hepatoprotective Influence of Hypericum perforatum Against Thioactamid-Induced Liver Fibrosis in Rats

Background:Hypericum perforatum (MEHP) is a broadly used therapeutic plant exhibiting numerous bioactivities. The present study evaluates acute toxicity and hepatoprotective effects of MEHP against thioacetamide (TAA)-induced liver injury in rats. Methods: The toxicity trial included a single oral administration of 2000 and 5000 mg/kg to rats. In the hepatoprotective experiment, 30 adult rats were arbitrarily clustered into 5 groups: Normal (A) and TAA control rats (B) treated with daily distilled water; reference rats received 3 oral doses/week of 50 mg/kg silymarin; D and E, rats received daily doses of 250 and 500 mg/kg MEHP, respectively. In addition, group B-E received 3 injections of 200 mg/kg TAA in a week for 60 days. Results: The results have shown a lack of any toxic signs in rats following oral administration of up to 5000 mg/kg. The hepatoprotective evaluations revealed a noticeably lower hepatic injury in MEHP-treated rats shown by reduced liver index and hepatocyte proliferation. Histopathological evaluation (H&E and Masson trichrome stains) showed a significant inhibitory potential of MEHP on the incidence rate of hepatic lesions represented by decreased liver necrosis and lower fibrous connective tissue proliferation initiated by TAA in rats. MEHP treatment meaningfully decreased proliferating cell nuclear antigen and alpha-SMA (myofibroblasts) in liver parenchymal tissues as well as improved redox (up-regulated SOD, CAT, GPx, and down-regulated MDA) and inflammatory state (decreased serum TNF-alpha and IL-6 cytokines) compared to fibrosis control rats. In addition, MEHP treatment caused significant restoration of serum liver biomarkers (enzymes and proteins) against TAA-induced hepatotoxicity. Conclusion: The present hepatoprotectives of MEHP could be attributed to its chemical contents (hypericin, hyperforin, quercitrin, and p-coumaric acid) that may validate it as a therapeutic additive for liver fibrosis after some pharmacological evaluations.