Background: The use of natural hepatoprotective remedies represents an important path in modern phytotherapy. Objectives: In this context, our research aims to evaluate the phytochemical composition and the hepatoprotective and oxidative stress reduction potential of an Arctium tomentosum Mill. root extract. Methods: The phenolic profile of the tested extract, prepared by the subcritical fluid-assisted method were qualitatively and quantitatively analyzed by spectrophotometrical and HPLC/DAD/ESI methods. In vitro antioxidant capacity was assessed using DPPH and FRAP assays. Hepatoprotective activity of the extract was assessed on a model of CCl4 experimentally induced hepatotoxicity in mice. Results: Phytochemical assays revealed the presence of important polyphenols, such as chlorogenic acid (17.20 ± 0.65 μg/mL) and acacetin 7-O-glucoside (56.80 ± 1.66 μg/mL). In vitro, the tested extract exhibited a significant oxidative stress reduction capacity, while in vivo it showed a dose-dependent hepatoprotective effect indicated by an improvement in plasma proteins profile and down-regulation of plasma transaminase activity (ALAT, ASAT, GGT). In liver tissue, the extract partially restored the activity of GPx, CAT, and SOD and attenuated lipid peroxidation. The protective effect of the A. tomentosum root extract was supported by the alleviation of histological injuries of the liver (centrilobular necrosis, granulocytic infiltrate, and fibrosis). Conclusions: The A. tomentosum subcritical fluid-assisted root extract proved to be able to provide a significant hepatoprotective effect mainly through an antioxidant mechanism.
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