Open AccessMulberry Leaf Diet Protects Against Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy Via Modulation of Oxidative Stress and MAPK ‐Mediated Apoptosis
Author(s) -
Arumugam Somasundaram,
Mito Sayaka,
Thandavarayan Rajarajan A.,
Giridharan Vijayasree V.,
Pitchaimani Vigneshwaran,
Karuppagounder Vengadeshprabhu,
Harima Meilei,
Nomoto Mayumi,
Suzuki Kenji,
Watanabe Kenichi
Publication year - 2013
Publication title -
cardiovascular therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 46
eISSN - 1755-5922
pISSN - 1755-5914
DOI - 10.1111/1755-5922.12029
Subject(s) - medicine , endocrinology , diabetic cardiomyopathy , oxidative stress , endoplasmic reticulum , fibrosis , endothelin 1 , cardiac function curve , myocarditis , dilated cardiomyopathy , myocardial fibrosis , cardiomyopathy , histopathology , heart failure , pathology , receptor , biology , biochemistry
Summary Aim of the study 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. Materials and 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 W estern 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 A zan– M allory 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. Conclusion 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.