en فارماکوگنوزی Pharmacognosy پژوهشي Original Research <strong>Background:</strong> Carbon tetrachloride (CCl4) as an organic solvent causes symptoms of acute and chronic liver injury, including necrosis, fat changes, liver cancer, and cirrhosis.&nbsp;Lepidium sativum contains flavonoids, alkaloids, and antioxidant components.<br> Objectives: This study aims to investigate the hepatic protection of&nbsp;L. Sativum Extract (LSE) on CCl4-induced hepatotoxicity in mice.<br> <strong>Methods: </strong>A total of 25 male mice were randomly divided into five groups (n=5): control (olive oil), CCl4, and 3 LSE groups. Except for the control group, all the mice received CCl4 (50%, 0.5 mL/kg) intraperitoneally twice a week for 4 weeks. The mice in the LSE groups were treated daily with LSE (200, 400, and 600 mg/kg) via IP injection. The animals were sacrificed 24 h after the last dose, and liver function parameters, such as Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Glutathione (GSH) were determined. Furthermore, 0.1 g of liver tissue was removed for histochemical analysis.<br> <strong>Results:</strong> Significant differences were observed in GSH, ALP, AST, and ALT levels between the CCI4 and the control groups. Compared to the CCl4 group, LSE treatment significantly decreased plasma ALT (P<0.05), AST in all doses (P<0.001), and ALP in 600 mg/kg (P<0.001). In addition, LSE treatment significantly increased GSH in 400 mg/kg (P<0.01) and 600 mg/kg (P<0.001).<br> <strong>Conclusion:</strong> LSE has hepatic protective activity against CCl4-induced injuries. The possible anti-hepatotoxic mechanisms may be related to&nbsp;the presence of flavonoids, triterpenes, alkaloids, tannin, and coumarins in the LSE by inhibiting the free radicals mediated damage. Alanine transaminase, Alkaline phosphatase, Aspartate aminotransferases, Glutathione, Toxic hepatitis 225 232 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-780-2&slc_lang=en&sid=1 Mohammad Shokrzadeh mslamuk@yahoo.com 100319475328460010212 100319475328460010212 No Department of Toxicology and Pharmacology, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Reza Khalvati 100319475328460010213 100319475328460010213 No Food and Drug Administration, Mazandaran University of Medical Sciences, Sari, Iran. Mohammad Hossein Hosseinzadeh iranmhhz@gmail.com 100319475328460010214 100319475328460010214 No Medicinal Plants Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Mona Ayatifard emrapharm@gmail.com 100319475328460010215 100319475328460010215 No Student Research Committee, School of Pharmacy, Ramsar International Campus, Mazandaran University of Medical Sciences, Ramsar, Iran. Emran Habibi emrapharm@yahoo.com 100319475328460010216 100319475328460010216 Yes Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.