euscaphic-acid and Chemical-and-Drug-Induced-Liver-Injury

An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues. Additionally, TA attenuated the APAP-induced production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6. Furthermore, the Western blot analysis showed that TA blocked the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation in APAP-injured liver tissues. TA also retained the superoxidase dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the liver. These results suggest that the hepatoprotective effects of TA may be related to its anti-inflammatory effect by decreasing thiobarbituric acid reactive substances (TBARS), iNOS, COX-2, TNF-α, IL-1β, and IL-6, and inhibiting NF-κB and MAPK activation. Antioxidative properties were also observed, as shown by heme oxygenase-1 (HO-1) induction in the liver, and decreases in lipid peroxides and ROS. Therefore, TA may be a potential therapeutic candidate for the prevention of APAP-induced liver injury by inhibiting oxidative stress and inflammation.

Topics: Acetaminophen; Alanine Transaminase; Animals; Aspartate Aminotransferases; Bilirubin; Catalase; Cells, Cultured; Chemical and Drug Induced Liver Injury; Cholesterol; Cyclooxygenase 2; Eriobotrya; Glutathione Peroxidase; Injections, Intraperitoneal; Interleukin-1beta; Interleukin-6; Liver; Male; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Protective Agents; Reactive Oxygen Species; Superoxide Dismutase; Triglycerides; Triterpenes; Tumor Necrosis Factor-alpha

The purpose of this study was to study the hepatoprotective effects of the most promising extract of the root from Rubus aleaefolius Poir. and to isolate and identify the active components. Various crude forms of Rubus aleaefolius have been evaluated for their effects on CCl(4)-induced acute liver injury in mice vivo experimental model. Treatment groups contained 5 sub-groups that were ethanol crude extract; the high/low dosage ethyl acetate or n-butanol fraction; extracted with ethyl acetate or n-butanol after the residues and major constituent; intragastrically administrated with 35 mg/kg; 35, 4.6 mg/kg; 35, 5.8 mg/kg; 35 mg/kg and 3.5 mg/kg for 7 days. The serum samples were collected for biological analysis and also carried out histopathological studies. The low-dosage ethyl acetate fraction was the most active when the fractions were compared. It was found to decrease AST, ALT; to prevent formation of hepatic MDA, NO and intensify the activity of SOD. The histopathological changes induced by CCl(4) were also significantly reduced. The separation revealed the presence of six constituents by a bioassay-guided fractionation, beta-Sitosterol (1), 1beta-Hydroxyeuscaphic acid (2), Oleanolic acid (3), Myrianthic acid (4), Euscaphic acid (5), and Tomentic acid (6). Among them, compounds 2, 4, 5 in Rubus aleaefolius root is reported here for the first time. 1beta-Hydroxyeuscaphic acid (major constituent) showed a tremendous activity and the results confirm the traditional uses of Rubus aleaefolius in treating hepatitis.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Liver; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Nitric Oxide; Oleanolic Acid; Phytotherapy; Plant Extracts; Plant Roots; Rosaceae; Sitosterols; Superoxide Dismutase; Triterpenes