Mulberry Leaf Diet Protects Against Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy Via Modulation of Oxidative Stress and MAPK-Mediated Apoptosis

作者：Arumugam Somasundaram; Mito Sayaka; Thandavarayan Rajarajan A; Giridharan Vijayasree V; Pitchaimani Vigneshwaran; Karuppagounder Vengadeshprabhu; Harima Meilei; Nomoto Mayumi; Suzuki Kenji; Watanabe Kenichi^*

来源：Cardiovascular Therapeutics, 2013, 31(6): 352-362.

DOI：10.1111/1755-5922.12029

• Cardiac fibrosis
• Dilated cardiomyopathy
• Experimental autoimmune myocarditis
• Mulberry leaf diet

Aim of the studyTo 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. %26lt;br%26gt;Materials and methodsIn 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 4weeks of immunization, the rats were fed with 5% MLD for 4weeks. 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. %26lt;br%26gt;ResultsOur 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. %26lt;br%26gt;ConclusionCollectively, 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 postmyocarditisdilated cardiomyopathy.

• 出版日期2013-12