Non-Communicable Diseases Group, Translational Health Science and Technology Institute (THSTI), Faridabad, 121001, India.
APCER Life Sciences, US-PVG Department, New Delhi, India.
Biomed Pharmacother. 2021 Jun;138:111316. doi: 10.1016/j.biopha.2021.111316. Epub 2021 Mar 5.
Cardiovascular diseases are the leading cause of death globally, and they are causing enormous socio-economic burden to the developed and developing countries. Allyl Methyl Sulfide (AMS) is a novel cardioprotective metabolite identified in the serum of rats after raw garlic administration. The present study explored the cardioprotective effect of AMS on thoracic aortic constriction (TAC)-induced cardiac hypertrophy and heart failure model in rats.
Thoracic aortic constriction (TAC) by titanium ligating clips resulted in the development of pressure overload-induced cardiac hypertrophy and heart failure model. Four weeks prior to TAC and for 8 weeks after TAC, Sprague Dawley (SD) rats were administered with AMS (25 and 50 mg/kg/day) or Enalapril (10 mg/kg/day).
We have observed AMS (25 and 50 mg/kg/day) intervention significantly improved structural and functional parameters of the heart. mRNA expression of fetal genes i.e., atrial natriuretic peptide (ANP), alpha skeletal actin (α-SA) and beta myosin heavy chain (β-MHC) were reduced in AMS treated TAC hearts along with decrease in perivascular and interstitial fibrosis. AMS attenuated lipid peroxidation and improved protein expression of endogenous antioxidant enzymes i.e., catalase and manganese superoxide dismutase (MnSOD) along with electron transport chain (ETC) complex activity. AMS increased mitochondrial fusion proteins i.e., mitofusin 1 (MFN1), mitofusin 2 (MFN2) and optic atrophy protein (OPA1), and reduced fission protein i.e., dynamin-related protein 1 (DRP1). Preliminary study suggests that AMS intervention upregulated genes involved in mitochondrial bioenergetics in normal rats. Further, in-vitro studies suggest that AMS reduced mitochondrial reactive oxygen species (ROS), preserved mitochondrial membrane potential and oxygen consumption rate (OCR) in isoproterenol-treated cardiomyoblast.
This study demonstrated that AMS protected cardiac remodelling, LV dysfunction and fibrosis in pressure overload-induced cardiac hypertrophy and heart failure model by improving endogenous antioxidants and mitochondrial function.
心血管疾病是全球范围内的主要死因，给发达国家和发展中国家造成了巨大的社会经济负担。烯丙基甲基硫醚（AMS）是一种在给予生大蒜后大鼠血清中发现的新型心脏保护代谢物。本研究探讨了 AMS 对大鼠胸主动脉缩窄（TAC）诱导的心肌肥厚和心力衰竭模型的心脏保护作用。
通过钛结扎夹进行胸主动脉缩窄（TAC），导致压力超负荷诱导的心肌肥厚和心力衰竭模型的发展。在 TAC 前 4 周和 TAC 后 8 周，给予 Sprague Dawley（SD）大鼠 AMS（25 和 50mg/kg/天）或依那普利（10mg/kg/天）。
我们观察到 AMS（25 和 50mg/kg/天）干预显著改善了心脏的结构和功能参数。在 AMS 治疗的 TAC 心脏中，胎儿基因的 mRNA 表达，即心房利钠肽（ANP）、α 骨骼肌肌动蛋白（α-SA）和β肌球蛋白重链（β-MHC）降低，同时血管周围和间质纤维化减少。AMS 减轻了脂质过氧化，并改善了内源性抗氧化酶的蛋白质表达，即过氧化氢酶和锰超氧化物歧化酶（MnSOD）以及电子传递链（ETC）复合物活性。AMS 增加了线粒体融合蛋白，即线粒体融合蛋白 1（MFN1）、线粒体融合蛋白 2（MFN2）和视蛋白（OPA1），并减少了分裂蛋白，即动力相关蛋白 1（DRP1）。初步研究表明，AMS 干预上调了正常大鼠中线粒体生物发生相关基因。此外，体外研究表明，AMS 减少了异丙肾上腺素处理的心肌细胞中的线粒体活性氧（ROS），并维持了线粒体膜电位和耗氧量（OCR）。
本研究表明，AMS 通过改善内源性抗氧化剂和线粒体功能，保护压力超负荷诱导的心肌肥厚和心力衰竭模型中的心脏重塑、LV 功能障碍和纤维化。
Zotero 插件