Inhibition of JNK along with activation of ERK1/2 MAPK pathways improve steatohepatitis among the rats.
OBJECTIVE
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.


CONCLUSIONS
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.
Aghazadeh
Safiyeh
S
Institute of Biochemistry and Biophysics, P.O. Box 13145-1384, University of Tehran, Tehran, Iran.
Yazdanparast
Razieh
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D031367:Teucrium / Q000737:chemistry
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C040618:teucrium extract; D008315:Malondialdehyde; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3