hyperoside and Chemical-and-Drug-Induced-Liver-Injury

To evaluate the effect of hyperin in cisplatin-induced liver injury in mice.. Mice were pretreated with hyperin at doses of 25 mg/kg and 50 mg/kg, respectively, for six days, and intraperitoneal injection of cisplatin (40 mg/kg) was administrated one hour after the final intragastrication of hyperin. Twenty-four hours later, blood and liver were collected for further research.. A single injection of cisplatin (40 mg/kg) for 24 h significantly increased serum alanine and aspartate aminotransferases (ALT/AST) and gamma glutamyl transferase (GGT) activities, whileas hyperin reversed cisplatin-induced such increases. Liver histopathological examination further demonstrated the protection of hyperin against cisplatin-induced liver injury. Further results showed hyperin reversed cisplatin-induced the increase in content of malondialdehyde (MDA) and the decrease in level of total antioxidant capacity (T-AOC) in liver. Moreover, hyperin increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione-s transferase (GST) in cisplatin-induced liver.. Hyperin inhibits cisplatin-induced hepatic oxidative stress, which contributes greatly to the amelioration of cisplatin-induced liver injury in mice.

Topics: Alanine Transaminase; Animals; Antineoplastic Agents; Antioxidants; Aspartate Aminotransferases; Catalase; Chemical and Drug Induced Liver Injury; Cisplatin; gamma-Glutamyltransferase; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Lipid Peroxidation; Liver; Male; Malondialdehyde; Mice, Inbred ICR; Oxidative Stress; Quercetin; Random Allocation; Reference Values; Reproducibility of Results; Superoxide Dismutase; Treatment Outcome

Acetaminphen (APAP) overdose leads to severe hepatotoxicity. Apocynum venetum L. (A. venetum) possess potent hepatoprotective effect. Hyperoside is one of the major compounds exist in Apocynum venetum L. and might be a potential agent to protect against APAP-induce liver injury. In this study, we investigated the effect of hyperoside on APAP hepatotoxicity in mice. Mice were treated intragastrically with hyperoside (10, 50 or 100 mg/kg) for 3 days before APAP (300 mg/kg) injection. APAP alone caused severe liver injury characterized by significantly increased serum aminotransferase levels, hepatic malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) formation, as well as liver superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) depletions. Hyperoside significantly attenuated APAP-induced liver damages in a dose dependent manner, and 100 mg/kg was the most effective dose. Further study confirmed that hyperoside was able to increase activities and mRNA expressions of uridine diphoshate glucuronosyltransferases (UGTs) and sulfotransferases (SULTs), as well as to inhibit CYP2E1 activities, and thereby suppressed toxic intermediate formation and promoted APAP hepatic detoxification. Nrf-2 activation might be involved in hyperoside induced up-regulation of phase II enzymes. Collectively, our data provide evidence that hyperoside protected the liver against APAP induced injury mainly by accelerating APAP harmless metabolism, implying that hyperoside can be considered as a potential natural hepatoprotective agent.

Topics: Acetaminophen; Animals; Chemical and Drug Induced Liver Injury; Cytochrome P-450 CYP2E1; Drug Overdose; Gene Expression Regulation, Enzymologic; Glucuronosyltransferase; Liver; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress; Quercetin; RNA, Messenger; Sulfotransferases; Tyrosine

Hyperin (HP) is a flavonoid compound found in various plants like Ericaceae, Guttifera and Celastraceae. The present study has revealed that HP has a variety of pharmacological effects including anti-oxidant, anticancer, and anti-coagulant, especially anti-inflammatory. However, the potential molecular mechanism of anti-inflammatory is still unrevealed. In this study, HP not only significantly attenuated inflammation in C57BL/6J mice with acute liver injury (ALI), but also reduced the expression of TNF-α and IL-6 in lipopolysaccharide (LPS)-induced RAW264.7 cells. Furthermore, our findings showed that HP remarkably induced the expression of PPAR-γ in vivo and in vitro. Interestingly, compared with the HP treatment group, a specific blocking agent of PPAR-γ T0070907 and PPAR-γ small interfering (si)-RNA-mediated silencing in RAW264.7 cells were used to evaluate the involvement of HP in alleviating LPS-induced inflammation. More importantly, over-expression of PPAR-γ had an opposite effect on the expression of TNF-α and IL-6 in LPS-induced RAW264.7 cells after treatment with HP. In addition, HP remarkably inhibited the expression of P-ERK1/2 and P-P38 MAPK. Taken together, all the above results indicate that HP may serve as an effective modulator of PPAR-γ, further down-regulating ERK1/2 and p38 MAPK during the pathogenesis of inflammation.

Topics: Animals; Anti-Inflammatory Agents; Chemical and Drug Induced Liver Injury; Interleukin-6; Lipopolysaccharides; Macrophages; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases; PPAR gamma; Quercetin; RAW 264.7 Cells; Tumor Necrosis Factor-alpha

In this study, the hepatoprotective effects of hyperoside (1), a flavonoid glycoside isolated from Artemisia capillaris, have been examined against carbon tetrachloride (CCl4)-induced liver injury. Mice were treated intraperitoneally with vehicle or 1 (50, 100, and 200 mg·kg(-1)) 30 min before and 2 h after CCl4 (20 μL·kg(-1)) injection. Levels of serum aminotransferases were increased 24 h after CCl4 injection, and these increases were attenuated by 1. Histological analysis showed that 1 prevented portal inflammation, centrizonal necrosis, and Kupffer cell hyperplasia. Lipid peroxidation was increased and hepatic glutathione content was decreased significantly after CCl4 treatment, and these changes were reduced by administration of 1. Protein and mRNA expression of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) and nuclear protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) significantly increased after CCl4 injection. Compound 1 suppressed TNF-α, iNOS, and COX-2 protein and mRNA expression and augmented HO-1 protein and mRNA expression and Nrf2 nuclear protein expression. These results suggest that 1 has protective effects against CCl4-induced acute liver injury, and this protection is likely due to enhancement of the antioxidative defense system and suppression of the inflammatory response.

Topics: Animals; Artemisia; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cyclooxygenase 2; Heme Oxygenase-1; Lipid Peroxidation; Mice; Molecular Structure; NF-E2-Related Factor 2; Nitric Oxide Synthase Type II; Quercetin; Tumor Necrosis Factor-alpha

Successive purification of the extract from Canarium album and Euphorbia nematocypha, guided by antihepatotoxic activity in primary cultured rat hepatocytes, led to the isolation of brevifolin (1), hyperin (2), ellagic acid (3) and 3,3'-di-O-methylellagic acid (4) as hepatoprotective compounds. Compounds 1,3 and 4 also reduced carbon tetrachloride (CCl4)-induced liver damage in mice. The hepatoprotective activities of 1, 2, 3 and 4 in vitro and in vivo are apparently due to their antioxidative effects, which were exhibited by further studies using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and CCl4-induced lipid peroxidation systems.

Topics: Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Ellagic Acid; Lipid Peroxidation; Medicine, Chinese Traditional; Mice; Plants, Medicinal; Quercetin; Rats