title: Mulberry leaf diet protects against progression of experimental autoimmune myocarditis to dilated cardiomyopathy via modulation of oxidative stress and MAPK-mediated apoptosis.
abstract: OBJECTIVE
  To examine the protective effects of dietary administration of Mulberry leaves (ML) on postmyocarditis dilated cardiomyopathy (DCM) focusing on oxidative and endoplasmic reticulum stresses and adverse myocardial remodeling.
  
  
  METHODS
  In this study, we used a rat model of cardiac myosin-induced experimental autoimmune myocarditis to test the effects of ML diet (MLD) (5%) on various markers of cardiac remodeling and function. After 4 weeks of immunization, the rats were fed with 5% MLD for 4 weeks. By the end of the study, echocardiography was performed to assess the myocardial dimensions. The heart tissue was used for histopathology and Western blotting analyses.
  
  
  RESULTS
  Our study showed that the postmyocarditis rats exhibited increased oxidative stress when compared with the control rats. MLD supplementation suppressed this change, compared with vehicle treatment. In addition, postmyocarditis rats showed significant elevation of the endoplasmic reticulum stress markers, which were prevented by the MLD supplementation. Similarly the vehicle-treated rats suffered with the adverse myocardial remodeling in the form of fibrosis as evidenced by the Azan-Mallory staining and immunohistochemistry for collagen-III levels, compared with the control rats. However, MLD treatment not only markedly attenuated cardiac fibrosis, but also improved the left ventricular ejection fraction and fractional shortening. Interestingly, the myocardial levels of endothelin-1, activated members of mitogen-activated protein kinase (MAPK) pathway, and vascular endothelial growth factor (VEGF) were significantly attenuated by MLD, indicating that the antihypertrophic effects of MLD are partially mediated via endothelin-1, MAPK, and VEGF pathway.
  
  
  CONCLUSIONS
  Collectively, these results suggest that supplementation of rats with 5% MLD has the ability to regulate cardiac remodeling and improves cardiac function and hence contributes to prevent the development of postmyocarditis dilated cardiomyopathy.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
authors.forename: Somasundaram
authors.initials: S
authors.lastname: Arumugam
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mito
authors.forename: Rajarajan A
authors.initials: RA
authors.lastname: Thandavarayan
authors.forename: Vijayasree V
authors.initials: VV
authors.lastname: Giridharan
authors.forename: Vigneshwaran
authors.initials: V
authors.lastname: Pitchaimani
authors.forename: Vengadeshprabhu
authors.initials: V
authors.lastname: Karuppagounder
authors.forename: Meilei
authors.initials: M
authors.lastname: Harima
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nomoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000150:complications*; D002311:Cardiomyopathy, Dilated / Q000517:prevention & control*; D004032:Diet; D018450:Disease Progression; D059865:Endoplasmic Reticulum Stress; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D031625:Morus; D009205:Myocarditis / Q000150:complications*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000032:analysis; D018515:Plant Leaves; D051381:Rats; D011917:Rats, Inbred Lew; D013481:Superoxides / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D010750:Phosphoproteins; D042461:Vascular Endothelial Growth Factor A; C079789:neutrophil cytosol factor 67K; D013481:Superoxides; D020928:Mitogen-Activated Protein Kinases
keywords: Cardiac fibrosis; Dilated cardiomyopathy; Experimental autoimmune myocarditis; Mulberry leaf diet