Studies on the modulatory role of phytochemicals against cardiac hypertrophy and myocardial fibrosis

Abstract

quotCardiovascular disease (CVD) is an ever-growing problem and is the most common newlinecause of death worldwide. The diseases related to the heart are steadily increasing day newlineby day in developing countries due to the increased affluence of industrialized societies newlinedue to dense caloric food and alcohol intake, smoking, and sedentary lifestyle. newlineResearchers enthusiastically explore traditional medicinal herbs nowadays and newlinescientific validation of their preclinical and clinical efficacy is being worked out. Thus, newlineherbal medicines are greatly emerging as effective alternatives or adjuncts to modern newlinemedicine. Oxidative damage and accumulation of extracellular matrix (ECM) newlinecomponents play a crucial role in the adverse outcome of cardiac hypertrophy. Evidence newlinesuggests that nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) can newlinemodulate oxidative damage and adverse myocardial remodeling. In the present study, newlinewe explored the phytochemicals by targeting the Nrf2 signaling and the expression of newlineECM components in both in vitro and in vivo experimental models of cardiac newlinehypertrophy. Daphnetin (Daph) is a coumarin obtained from the plant genus Daphne newlinespecies that exerts anti-oxidative and anti-inflammatory properties. Herein, we newlineinvestigated the roles of Daph in transverse aortic constriction (TAC)-induced cardiac newlinehypertrophy and fibrosis in mice. TAC-induced alterations in cardiac hypertrophy newlinemarkers, histopathological changes, and cardiac function were markedly ameliorated by newlineoral administration of Daph in mice. We found that Daph significantly reduced the newlinereactive oxygen species (ROS) generation, increased the nuclear translocation of Nrf2, newlineand consequently, reinstated the protein levels of NAD(P)H quinone dehydrogenase 1 newline(NQO1), heme oxygenase-1 (HO-1), and other antioxidants in the heart. Besides, Daph newlinesignificantly inhibited the TAC-induced accumulation of ECM components, including newlineand#945;-smooth muscle actin (and#945;-SMA), collagen I, collagen III, and fibronectin, and interfered newlinewith the TGF-and#946;1/Smad