| Summary: | This study investigated the druggability, pharmacokinetics and ethyl acetate extract of <i>Teucrium polium</i> (EA <i>T. polium</i>), from Ha'il, and the protective effect against carbon tetrachloride (CCl<sub>4</sub>) induced liver cirrhosis in rats. The total antioxidant capacity (TAC) and scavenging activity of the extract were examined. The in vivo protective study was based on the use of an animal model of CCl<sub>4</sub>-induced liver cirrhosis. Four groups of rats have been used: Group I: control rats; Group II: received CCl<sub>4</sub> in olive oil (0.5 mL/kg); Group III: received the EA <i>T. polium</i> (25 mg/kg) of pretreatment for seven days by gavage then CCl<sub>4</sub> in olive oil by gavage for 15 days. Group IV: received the EA of <i>T. polium</i> for seven days (25 mg/kg). EA <i>T. polium</i> was found to possess significant antioxidant capacity. CCl<sub>4</sub> caused a hepatotoxicity associated increase in both levels of AST and ALT, which were reduced back to normal values following EA <i>T. polium</i> pretreatment. Hepatotoxicity associated structural modifications of liver tissues and increase in thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and carbonyl proteins (CP), associated decreases in several assessed antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). The in vivo findings on the protective effect of <i>T. polium</i> were supported by its druggability, its pharmacokinetic properties and molecular docking assays. These results confirm the modulatory antioxidant and hepatoprotective potential of <i>T. polium</i> in this experimental liver cirrhosis model. <i>T. polium</i> phytochemicals are good candidates for further pharmaceutical explorations and drug design.
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