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

Abstract

SUMMARYAim 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 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. 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.

Naringenin ameliorates daunorubicin induced nephrotoxicity by mitigating AT1R, ERK1/2-NFκB p65 mediated inflammation

“…The remaining excised kidneys were cut into 2 mm thick transverse slices and fixed in 10% formalin. Sections of 3-5 μm thickness were stained with hematoxylin and eosin (H&E) or Masson trichrome for histological examination [15]. A histomorphological evaluation of all the renal sections was carried out in a blinded fashion.…”

LTBP2 knockdown by siRNA reverses myocardial oxidative stress injury, fibrosis and remodelling during dilated cardiomyopathy

“…Moreover, approximately 20%‐50% of affected patients have a family history, suggesting that heredity is an important cause of this disease . Of crucial importance, increased oxidative stress has been implicated in the adverse cardiac remodelling associated with DCM, which may trigger myocardial inflammation, cardiomyocyte dysfunction and apoptosis . Similarly, it is suggested that in the development of DCM, oxidative stress promotes cellular senescence and death, and is concomitantly associated with the decreased cardiac function .…”

Impact of polyphenolic components from mulberry on apoptosis of vascular smooth muscle cells

“…10 Besides, a mulberry leaf diet was also reported to protect against the progression of experimental autoimmune myocarditis to dilated cardiomyopathy via modulation of oxidative stress and MAPK-mediated apoptosis. 11 However, the functional components that inhibited apoptosis in the above studies were not isolated. Transcription factor p53 has been reported to mediate apoptosis by increasing the expression of cell surface Fas on human VSMCs.…”

“…Mulberry fruit extract was also reported to protect pancreatic β cells against hydrogen peroxide‐induced oxidative stress and associated apoptotic cell death . Besides, a mulberry leaf diet was also reported to protect against the progression of experimental autoimmune myocarditis to dilated cardiomyopathy via modulation of oxidative stress and MAPK‐mediated apoptosis . However, the functional components that inhibited apoptosis in the above studies were not isolated.…”