PMID- 19748164 OWN - NLM STAT- MEDLINE DCOM- 20100928 LR - 20220321 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 29 IP - 3 DP - 2010 Jun TI - Inhibition of JNK along with activation of ERK1/2 MAPK pathways improve steatohepatitis among the rats. PG - 381-5 LID - 10.1016/j.clnu.2009.08.014 [doi] AB - BACKGROUND & AIMS: Oxidative stress-induced hepatocyte apoptosis is implicated in the onset of non-alcoholic steatohepatitis (NASH). Regarding the pronounced roles of mitogen activated protein kinases (MAPKs) in oxidative stress-induced cellular damages and the development of NASH, we evaluated the effect of Teucrium polium ethyl acetate (EtoAc) extract on rats with NASH and on the modulation of MAPKs activities. METHODS: To induce NASH, a methionine choline deficient diet (MCD) was given to N-Mary rats. These animals were then compared to the control group receiving normal diet and/or MCD diet plus EtoAc extract (0.5g/kg/day). After 8 weeks, liver histopathology, malondialdehyde (MDA) and immunoblot analyses of caspase-3 cleavage, ERK/pERK and JNK/pJNK were examined. RESULTS: Simultaneous treatments with MCD diet and the EtoAc extract resulted in pronounced improvements in liver steatosis, ballooning degeneration and inflammation. Elevated MDA and caspase-3 levels among MCD-fed rats were also markedly decreased. In addition, the EtoAc extract treatments caused significant reduction in the phosphorylated form of JNK along with an increase in the phosphorylated level of ERK1/2. CONCLUSION: These results indicate that the anti-apoptotic effect of T. polium extract is mediated through inhibition of ROS generation. Moreover, the inhibitory effect of T. polium on the development and progression of NASH is apparently governed by the attenuation of JNK activation and augmentation of ERK1/2 activity through phosphorylation. CI - Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. FAU - Aghazadeh, Safiyeh AU - Aghazadeh S AD - Institute of Biochemistry and Biophysics, P.O. Box 13145-1384, University of Tehran, Tehran, Iran. FAU - Yazdanparast, Razieh AU - Yazdanparast R LA - eng PT - Journal Article DEP - 20090911 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Enzyme Activators) RN - 0 (Enzyme Inhibitors) RN - 0 (Plant Extracts) RN - 0 (teucrium extract) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 3.4.22.- (Casp3 protein, rat) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Anti-Inflammatory Agents/isolation & purification/pharmacology/therapeutic use MH - Antioxidants/isolation & purification/pharmacology/therapeutic use MH - Caspase 3/metabolism MH - Enzyme Activation/drug effects MH - Enzyme Activators/isolation & purification/pharmacology/*therapeutic use MH - Enzyme Inhibitors/isolation & purification/pharmacology/*therapeutic use MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Fatty Liver/drug therapy/metabolism/pathology/*prevention & control MH - JNK Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism MH - Liver/drug effects/metabolism/pathology MH - MAP Kinase Signaling System/*drug effects MH - Male MH - Malondialdehyde/metabolism MH - Oxidative Stress/drug effects MH - Phosphorylation/drug effects MH - *Phytotherapy MH - Plant Components, Aerial/chemistry MH - Plant Extracts/isolation & purification/pharmacology/therapeutic use MH - Rats MH - Teucrium/chemistry EDAT- 2009/09/15 06:00 MHDA- 2010/09/30 06:00 CRDT- 2009/09/15 06:00 PHST- 2009/03/03 00:00 [received] PHST- 2009/07/28 00:00 [revised] PHST- 2009/08/14 00:00 [accepted] PHST- 2009/09/15 06:00 [entrez] PHST- 2009/09/15 06:00 [pubmed] PHST- 2010/09/30 06:00 [medline] AID - S0261-5614(09)00172-1 [pii] AID - 10.1016/j.clnu.2009.08.014 [doi] PST - ppublish SO - Clin Nutr. 2010 Jun;29(3):381-5. doi: 10.1016/j.clnu.2009.08.014. Epub 2009 Sep 11.