cytochrome-c-t and linarin

As we all know, oxidative stress was one of the most important causes of ischemia-reperfusion injury. And it was reported that Nrf-2 as an important regulator for oxidative stress could be activated by Linarin. Thus it would be interesting to find whether Linarin could inhibit ischemia-reperfusion injury through activating Nrf-2.. In this study, cell activity was detected by MTT assay and caspase-3 activity detection kit. And the expressions or activities of some signal proteins were evaluated by western-blot or activity detection kits. At last, the effect and mechanism of Linarin on heart tissues were verified in the ischemia-reperfusion model of isolated hearts.. The proliferation activity of cell was inhibited while the apoptosis rate was increased after hypoxia-reoxygenation. However, Linarin could inhibit these two variations. It was found that these effects of Linarin were related with the activation of Nrf-2 through PI3K/Akt signaling pathway. Meanwhile, the anti-oxidative enzymes, regulated by Nrf-2, were enhanced to against the oxidative stress caused by hypoxia-reoxygenation. And with the inhibition of oxidative stress, some proliferation and apoptosis related proteins such as NF-kB and Cytochrome C were adjusted to support the viability of cells. At last, these results were verified in the ischemia reperfusion experiment of isolated hearts.. From this study, we assured that LIN could protect myocardial tissue from ischemia-reperfusion through activating Nrf-2.

Topics: Animals; Antioxidants; Apoptosis; Cell Line; Cytochromes c; Glycosides; Heart; Myocardial Reperfusion Injury; Myocardium; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinases; Protective Agents; Rats; Signal Transduction

Linarin was isolated from Chrysanthemum indicum L. Fulminant hepatic failure is a serious clinical syndrome that results in massive inflammation and hepatocyte death. Apoptosis is an important cellular pathological process in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury, and regulation of liver apoptosis might be an effective therapeutic method for fulminant hepatic failure. This study examined the cytoprotective mechanisms of linarin against GalN/LPS-induced hepatic failure. Mice were given an oral administration of linarin (12.5, 25 and 50mg/kg) 1h before receiving GalN (800 mg/kg)/LPS (40 μg/kg). Linarin treatment reversed the lethality induced by GalN/LPS. After 6h of GalN/LPS injection, the serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor (TNF)-α, interleukin-6 and interferon-γ were significantly elevated. GalN/LPS increased toll-like receptor 4 and interleukin-1 receptor-associated kinase protein expression. These increases were attenuated by linarin. Linarin attenuated the increased expression of Fas-associated death domain and caspase-8 induced by GalN/LPS, reduced the cytosolic release of cytochrome c and caspase-3 cleavage induced by GalN/LPS, and reduced the pro-apoptotic Bim phosphorylation induced by GalN/LPS. However, linarin increased the level of anti-apoptotic Bcl-xL and phosphorylation of STAT3. Our results suggest that linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways.

Topics: Alanine Transaminase; Animals; Apoptosis; Apoptosis Regulatory Proteins; Aspartate Aminotransferases; Bcl-2-Like Protein 11; bcl-X Protein; Caspase 3; Caspase 8; Cytochromes c; Cytoprotection; Cytosol; Fas-Associated Death Domain Protein; Galactosamine; Glycosides; Interferon-gamma; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; Membrane Proteins; Mice; Phosphorylation; Proteolysis; Proto-Oncogene Proteins; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha