Although there have been significant advances in the treatment of heart failure in recent years,chronic heart failure remains a leading cause of cardiovascular disease-related death.Many studies have found that target...Although there have been significant advances in the treatment of heart failure in recent years,chronic heart failure remains a leading cause of cardiovascular disease-related death.Many studies have found that targeted cardiac metabolic remodeling has good potential for the treatment of heart failure.However,most of the drugs that increase cardiac energy are still in the theoretical or testing stage.Some research has found that botanical drugs not only increase myocardial energy metabolism through multiple targets but also have the potential to restore the balance of myocardial substrate metabolism.In this review,we summarized the mechanisms by which botanical drugs(the active ingredients/formulas/Chinese patent medicines)improve substrate utilization and promote myocardial energy metabolism by activating AMP-activated protein kinase(AMPK),peroxisome proliferator-activated receptors(PPARs)and other related targets.At the same time,some potential protective effects of botanical drugs on myocardium,such as alleviating oxidative stress and dysbiosis signaling,caused by metabolic disorders,were briefly discussed.展开更多
Objective To investigate the different effects of an angiotensin Ⅱ type 1 (AT 1) receptor antagonist, losartan, and an angiotensin converting enzyme (ACE) inhibitor, fosinopril, on cardiomyocyte apoptosis, myocardi...Objective To investigate the different effects of an angiotensin Ⅱ type 1 (AT 1) receptor antagonist, losartan, and an angiotensin converting enzyme (ACE) inhibitor, fosinopril, on cardiomyocyte apoptosis, myocardial fibrosis, and angiotensin Ⅱ (AngⅡ) in the left ventricle of spontaneously hypertensive rats (SHRs) Methods SHRs of 16 week old were randomly divided into 3 groups: SHR L (treated with losartan, 30 mg·kg 1 ·d 1 ), SHR F (treated with fosinopril, 10 mg·kg 1 ·d 1 ), and SHR C (treated with placebo) Each group consisted of 10 rats Five rats, randomly selected from each group, were killed at the 8th and 16th week after treatment Cardiomyocyte apoptosis, collagen volume fraction (CVF), perivascular collagen area (PVCA) and AngⅡ concentrations of plasma and myocardium were examined Results Compared with the controls at the 8th and 16th week, systolic blood pressures were similarly decreased in both treatment groups Left ventricular weight and left ventricular mass indexes were significantly lower in both treatment groups However, the latter parameter at the 16th week was reduced to a less extent in the fosinopril group than that in the losartan group Compared with the controls, cardiomycyte apoptotic index was significantly reduced at the 8th week only in the fosinopril group, and at the 16th week in both treatment groups The index of the fosinopril group was lower than that of the losartan group at the latter endpoint examined Compared with the controls, the left ventricular collagen volume fraction and perivascular collagen area at the 8th and 16th weeks were significantly reduced in the SHRs treated with either fosinopril or losartan However, the collagen volume fraction at the latter endpoint in the fosinopril group was lower than that in the losartan group Compared with the controls at endpoints, plasma and myocardium Ang Ⅱ levels were significantly increased in the losartan group However, plasma Ang Ⅱ concentrations were not altered, and myocardium AngⅡ concentrations at the 8th and 16th weeks were significantly reduced in the fosinopril group Conclusions Both losartan and fosinopril could effectively inhibit cardiomyocyte apoptosis and myocardial fibrosis and reverse heart hypertrophy Fosinopril may be more effective in these cardioprotective effects, suggesting that the effects of both drugs are related to the inhibition of myocardium renin angiotension aldsterone system展开更多
目的基于网络药理学和分子对接方法探究“麦冬-五味子”药对治疗心肌纤维化的作用机制。方法运用TCMSP数据库及HERB数据库筛选“麦冬-五味子”药对药物成分和靶点,运用GeneCards数据库、Disgenet数据库、OMIM数据库筛选疾病靶点,获取共...目的基于网络药理学和分子对接方法探究“麦冬-五味子”药对治疗心肌纤维化的作用机制。方法运用TCMSP数据库及HERB数据库筛选“麦冬-五味子”药对药物成分和靶点,运用GeneCards数据库、Disgenet数据库、OMIM数据库筛选疾病靶点,获取共同靶点;通过Cytoscape软件构建“药物活性成分-疾病-靶点”网络模型;利用微生信平台进行基因本体论功能富集分析(gene ontology,GO)和京都基因与基因组百科全书富集分析(kyoto encyclopedia of genes and genomes,KEGG);利用STRING数据库构建蛋白互作网络;通过Auto Dock Tools1.5.6软件进行分子对接验证。结果“麦冬-五味子”药对中共筛选得到戈米辛M2、五味子酚乙、麦冬二氢高异黄酮B等85个活性成分,主要作用于HSP90AA1、AKT1、SRC等163个心肌纤维化靶点上,主要富集在脂质与动脉粥样硬化信号通路、糖尿病并发症中的age-rage信号通路、癌症发病途径信号通路等相关通路上。结论“麦冬-五味子”药对主要通过调控炎性反应、氧化应激、脂质沉积、细胞增殖凋亡等多种生物过程来抑制心肌纤维化。展开更多
基金Supported by the National Key Research&Development Program (No.2019YFC1708602)。
文摘Although there have been significant advances in the treatment of heart failure in recent years,chronic heart failure remains a leading cause of cardiovascular disease-related death.Many studies have found that targeted cardiac metabolic remodeling has good potential for the treatment of heart failure.However,most of the drugs that increase cardiac energy are still in the theoretical or testing stage.Some research has found that botanical drugs not only increase myocardial energy metabolism through multiple targets but also have the potential to restore the balance of myocardial substrate metabolism.In this review,we summarized the mechanisms by which botanical drugs(the active ingredients/formulas/Chinese patent medicines)improve substrate utilization and promote myocardial energy metabolism by activating AMP-activated protein kinase(AMPK),peroxisome proliferator-activated receptors(PPARs)and other related targets.At the same time,some potential protective effects of botanical drugs on myocardium,such as alleviating oxidative stress and dysbiosis signaling,caused by metabolic disorders,were briefly discussed.
文摘Objective To investigate the different effects of an angiotensin Ⅱ type 1 (AT 1) receptor antagonist, losartan, and an angiotensin converting enzyme (ACE) inhibitor, fosinopril, on cardiomyocyte apoptosis, myocardial fibrosis, and angiotensin Ⅱ (AngⅡ) in the left ventricle of spontaneously hypertensive rats (SHRs) Methods SHRs of 16 week old were randomly divided into 3 groups: SHR L (treated with losartan, 30 mg·kg 1 ·d 1 ), SHR F (treated with fosinopril, 10 mg·kg 1 ·d 1 ), and SHR C (treated with placebo) Each group consisted of 10 rats Five rats, randomly selected from each group, were killed at the 8th and 16th week after treatment Cardiomyocyte apoptosis, collagen volume fraction (CVF), perivascular collagen area (PVCA) and AngⅡ concentrations of plasma and myocardium were examined Results Compared with the controls at the 8th and 16th week, systolic blood pressures were similarly decreased in both treatment groups Left ventricular weight and left ventricular mass indexes were significantly lower in both treatment groups However, the latter parameter at the 16th week was reduced to a less extent in the fosinopril group than that in the losartan group Compared with the controls, cardiomycyte apoptotic index was significantly reduced at the 8th week only in the fosinopril group, and at the 16th week in both treatment groups The index of the fosinopril group was lower than that of the losartan group at the latter endpoint examined Compared with the controls, the left ventricular collagen volume fraction and perivascular collagen area at the 8th and 16th weeks were significantly reduced in the SHRs treated with either fosinopril or losartan However, the collagen volume fraction at the latter endpoint in the fosinopril group was lower than that in the losartan group Compared with the controls at endpoints, plasma and myocardium Ang Ⅱ levels were significantly increased in the losartan group However, plasma Ang Ⅱ concentrations were not altered, and myocardium AngⅡ concentrations at the 8th and 16th weeks were significantly reduced in the fosinopril group Conclusions Both losartan and fosinopril could effectively inhibit cardiomyocyte apoptosis and myocardial fibrosis and reverse heart hypertrophy Fosinopril may be more effective in these cardioprotective effects, suggesting that the effects of both drugs are related to the inhibition of myocardium renin angiotension aldsterone system
文摘目的基于网络药理学和分子对接方法探究“麦冬-五味子”药对治疗心肌纤维化的作用机制。方法运用TCMSP数据库及HERB数据库筛选“麦冬-五味子”药对药物成分和靶点,运用GeneCards数据库、Disgenet数据库、OMIM数据库筛选疾病靶点,获取共同靶点;通过Cytoscape软件构建“药物活性成分-疾病-靶点”网络模型;利用微生信平台进行基因本体论功能富集分析(gene ontology,GO)和京都基因与基因组百科全书富集分析(kyoto encyclopedia of genes and genomes,KEGG);利用STRING数据库构建蛋白互作网络;通过Auto Dock Tools1.5.6软件进行分子对接验证。结果“麦冬-五味子”药对中共筛选得到戈米辛M2、五味子酚乙、麦冬二氢高异黄酮B等85个活性成分,主要作用于HSP90AA1、AKT1、SRC等163个心肌纤维化靶点上,主要富集在脂质与动脉粥样硬化信号通路、糖尿病并发症中的age-rage信号通路、癌症发病途径信号通路等相关通路上。结论“麦冬-五味子”药对主要通过调控炎性反应、氧化应激、脂质沉积、细胞增殖凋亡等多种生物过程来抑制心肌纤维化。
