title: Protective mechanisms of berberine against experimental autoimmune myocarditis in a rat model.
abstract: Berberine, an alkaloid derivative extracted from numerous plants of the general Berberis and Coptis, has been reported to have immunomodulatory effects against immune-mediated disorders in emerging studies. In this study, the effects of berberine and its underlying molecular mechanisms were investigated from the myosin-induced myocardial injury in rats. Lewis rats were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis (EAM), treated with berberine and specific JAK inhibitor AG490 as a positive control. Our data showed that both berberine and AG490 significantly reduced the impaired cardiac function and the pathophysiological severity, impeded high levels of anti-cardiac myosin antibody of EAM rats. Th17 and Th1 cells as well as their cytokines IL-17 and IFN-γ were up-regulated in EAM. However, the excessive increase of Th17/Th1 responses was restored by berberine and AG490. We also examined the expression level of phosphorylated proteins of JAK-STAT pathway which has a key role in the Th17 and Th1 lineage commitment. The phosphorylated (p)-STAT1,STAT3 and STAT4 increased significantly in EAM, while berberine notably attenuated their excessive expression. This effect of berberine was equivalent to that of AG490 blockade. Our current study demonstrated that berberine could ameliorate EAM and the underling mechanisms may be due to the fact that berberine differentially modulates the activities of p-STAT1, p-STAT3 and p-STAT4 to suppress Th17 and Th1 cell differentiation.
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, PR China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, PR China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, PR China. Electronic address: doctoryuanht@163.com.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005355:Fibrosis; D007249:Inflammation / Q000473:pathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009205:Myocarditis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011917:Rats, Inbred Lew; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D020011:Protective Agents; D050791:STAT Transcription Factors; D001599:Berberine; D009218:Myosins
keywords: Berberine; Experimental autoimmune myocarditis; JAK-STAT; Th1; Th17