Isorhamnetin-3-O-galactoside Protects against CCl₄-Induced Hepatic Injury in Mice

Abstract

This study was performed to examine the hepatoprotective effect of isorhamnetin-3-O-galactoside, a flavonoid glycoside isolated from Artemisia capillaris Thunberg (Compositae), against carbon tetrachloride (CCl4)-induced hepatic injury. Mice were treated intraperitoneally with vehicle or isorhamnetin-3-O-galactoside (50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20 μl/kg) injection. Serum aminotransferase activities and hepatic level of malondialdehyde were significantly higher after CCl4 treatment, and these increases were attenuated by isorhamnetin-3-O-galactoside. CCl4 markedly increased serum tumor necrosis factor-α level, which was reduced by isorhamnetin-3-O-galactoside. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase- 2 (COX-2), and heme oxygenase-1 (HO-1) protein and their mRNA expression levels were significantly increased after CCl4 injection. The levels of HO-1 protein and mRNA expression levels were augmented by isorhamnetin-3-O-galactoside, while isorhamnetin- 3-O-galactoside attenuated the increases in iNOS and COX-2 protein and mRNA expression levels. CCl4 increased the level of phosphorylated c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38, and isorhamnetin-3-O-galactoside reduced these increases. The nuclear translocation of nuclear factor kappa B (NF-κB), activating protein-1, and nuclear factor erythroid 2-related factor 2 (Nrf2) were signifi cantly increased after CCl4 administration. Isorhamnetin-3-O-galactoside attenuated the increases of NF-κB and c-Jun nuclear translocation, while it augmented the nuclear level of Nrf2. These results suggest that isorhamnetin-3-O-galactoside ameliorates CCl4-induced hepatic damage by enhancing the anti-oxidative defense system and reducing the inflammatory signaling pathways.

Grape-Leaf Extract Attenuates Alcohol-Induced Liver Injury via Interference with NF-κB Signaling Pathway

“…SOD activity was not changed by EtOH administration in the current study, which was in accordance with other results [38,39], which could be due to a defense mechanism initiated by the liver. The antioxidant effects observed for GLE (current study) could be partly attributed to the activation of nuclear factor erythroid 2 related factor 2 (Nrf2), a master transcription factor for antioxidant response, reported to be mediated by the secondary metabolites (e.g., apigenin derivative [5,40], epicatechin [41], quercetin derivatives [3,42], caffeic acid [43,44], rosmarinic acid derivatives [45,46], and isorhamnetin derivatives [4,47]) present in the extract. Future studies are needed to clearly address the effect of GLE on Nrf2 activation.…”

Molecular mechanism and therapeutic modulation of high mobility group box 1 release and action: an updated review

“…A number of other herbal components have been proven protective against lethal infection or injury by attenuating systemic HMGB1 release or action ( Table 2 ), raising further interest in future clinical studies. Importantly, these herbal components have also been proven beneficial in animal models of ischemia [148-155], trauma [156,157], crush injury [158], hemorrhage [159], radiation [160,161], chemical toxemia [162,163]. Nevertheless, it remains unknown whether the protective effects are associated with inhibition of HMGB1 release or chemokine/cytokine activities during injury.…”

Hepatoprotective activity of aqueous methanolic extract of <i>Morus nigra</i> against paracetamol-induced hepatotoxicity in mice

“…Qualitative determination of these flavonoids was conducted by HPLC analysis. (Kim et al, 2012) and quercetin (Janbaz et al, 2004), all are famous for its anti-oxidant and hepatoprotective potential. Due to its edible nature, easy accessibility and economical factor, M. nigra can be a good source of active continents having tolerable potential for liver health.…”