title: Allicin protects against cardiac hypertrophy and fibrosis via attenuating reactive oxygen species-dependent signaling pathways.
abstract: Increased oxidative stress has been associated with the pathogenesis of chronic cardiac hypertrophy and heart failure. Since allicin suppresses oxidative stress in vitro and in vivo, we hypothesized that allicin would inhibit cardiac hypertrophy through blocking oxidative stress-dependent signaling. We examined this hypothesis using primary cultured cardiac myocytes and fibroblasts and one well-established animal model of cardiac hypertrophy. Our results showed that allicin markedly inhibited hypertrophic responses induced by Ang II or pressure overload. The increased reactive oxygen species (ROS) generation and NADPH oxidase activity were significantly suppressed by allicin. Our further investigation revealed this inhibitory effect on cardiac hypertrophy was mediated by blocking the activation of ROS-dependent ERK1/2, JNK1/2 and AKT signaling pathways. Additional experiments demonstrated allicin abrogated inflammation and fibrosis by blocking the activation of nuclear factor-κB and Smad 2/3 signaling, respectively. The combination of these effects resulted in preserved cardiac function in response to cardiac stimuli. Consequently, these findings indicated that allicin protected cardiac function and prevented the development of cardiac hypertrophy through ROS-dependent mechanism involving multiple intracellular signaling.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Sun Yat-Sen University, 510080 Guangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
authors.forename: Qi-Zhu
authors.initials: QZ
authors.lastname: Tang
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Dong
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhu
authors.forename: Lang
authors.initials: L
authors.lastname: Wang
authors.forename: Zhou-Yan
authors.initials: ZY
authors.lastname: Bian
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D006332:Cardiomegaly / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004220:Disulfides; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013441:Sulfinic Acids / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004220:Disulfides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013441:Sulfinic Acids; C006452:allicin