ag-490 and isoliquiritigenin

To examine whether isoliquiritigenin (ISL) can attenuate myocardial ischemiareperfusion (MI/R) injury in rats by inducing metallothionein (MT) through activation of janus kinase 2 (JAK 2)/signal transducers and activators of transcription 3 (STAT 3) pathway.. The experimental model of MI/R in rats was generated by 30 min of ischemia and reperfusion for 2 h. The mRNA expression of MT, COX-2, and iNOS were measured by RT-PCR. The protein expressions of MT, JAK/STAT, extracellular signal-regulated kinase (ERK), and Akt were determined by Western blotting in the absence or presence of a JAK kinase inhibitor, tyrphostin AG490 (1.0 mg/kg, iv, 1 h before ischemia).. Pretreatment with ISL markedly decreased the severity of reperfusion-induced arrhythmias and myocardial infarct size. In the ISL 20 mg/kg group, the activities of lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) were reduced by 38.4% and 51.3% when compared with the vehicle group. Increased JAK 2/STAT 3 phosphorylation was accompanied by increased synthesis of MT but not of COX-2 or iNOS in ISL-treated groups. AG490 can significantly weaken ISL-induced cardioprotection and prevent the increase of MT expression and JAK 2/STAT 3 phosphorylation.. ISL protected MI/R injury through activation of JAK 2/STAT 3 signal transduction pathway, which might be involved in mediating the upregulation of MT expression.

Topics: Animals; Chalcones; Creatine Kinase; Janus Kinase 2; L-Lactate Dehydrogenase; Male; Metallothionein; Myocardial Reperfusion Injury; Phosphorylation; Protective Agents; Protein-Tyrosine Kinases; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Tyrphostins