Juan Hu1, Pan Cheng1, Guang-Yao Huang1, Guo-Wei Cai1, Feng-Zhen Lian1, Xiao-Yun Wang1, Shan Gao2. 1. Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China. 2. Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China. Electronic address: gaoshan@ahmu.edu.cn.
Abstract
BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection on cardiovascular diseases like hypertension and myocarditis. PURPOSE: To elucidate the protective effects of XJEK on heart failure (HF) induced by myocardial infarction (MI) through the amelioration of inflammation, oxidative stress (OS) and endothelial dysfunction(ED). MATERIALS AND METHODS: Fifty-seven male KM mice were randomized into the following six groups (n = 9-10 for each): control group, model group, MI+XJEK low dose group(XJEKL) group, MI+XJEK middle dose group(XJEKM), MI+XJEK high dose group(XJEKH), and MI+fosinopril group (positive control group). After treatment for four weeks, electrocardiography (ECG) and haemodynamics were recorded. Serum and tissues were collected for further analysis. Endothelium-dependent relaxation induced by acetylcholine was assessed in isolated thoracic aorta ring experiment. Hematoxylin and eosin (HE) and Van Gieson (VG) staining were used to detect the pathological changes of heart and thoracic aorta. Colorimetric analysis was employed to determine serum nitric oxide level (NO), malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity. ELISA was used to detect serum B-type natriuretic peptide (BNP) and serum inflammatory cytokines, as well as endothelial NO synthetase (eNOS), angiotensinII (Ang II) and endothelin-1(ET-1) concentration in both serum and cardiac tissues. Immunohistochemistry and Western blotting (WB) were employed to detect eNOS and inflammatory cytokine expressions in cardiac tissues. RESULTS: XJEK administration markedly ameliorated cardiac dysfunction and abnormal ECG manifested by decreased weight/body weight (HW/BW) ratio, BNP and remedied hypertrophy of cardiomyocytes and deposition of collagen, which might be in part attributed to the increased SOD and decreased MDA in serum. Furthermore, XJEK administration improved ED with boosted eNOS activities in serum and cardiac tissues, as well as up-regulated NO levels in serum, down-regulated Ang II and ET-1 content in serum and cardiac tissues. Lastly, protein expression of pro-inflammation cytokines significantly decreased, and anti-inflammatory cytokine was significantly enhanced in serum and cardiac tissues compared to model group. CONCLUSION: XJEK may exert beneficial effects on HF induced by MI in mice, and the underlying mechanism may be attributable to the amelioration of ED, anti-OS and anti-inflammation effects.
BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection on cardiovascular diseases like hypertension and myocarditis. PURPOSE: To elucidate the protective effects of XJEK on heart failure (HF) induced by myocardial infarction (MI) through the amelioration of inflammation, oxidative stress (OS) and endothelial dysfunction(ED). MATERIALS AND METHODS: Fifty-seven male KM mice were randomized into the following six groups (n = 9-10 for each): control group, model group, MI+XJEK low dose group(XJEKL) group, MI+XJEK middle dose group(XJEKM), MI+XJEK high dose group(XJEKH), and MI+fosinopril group (positive control group). After treatment for four weeks, electrocardiography (ECG) and haemodynamics were recorded. Serum and tissues were collected for further analysis. Endothelium-dependent relaxation induced by acetylcholine was assessed in isolated thoracic aorta ring experiment. Hematoxylin and eosin (HE) and Van Gieson (VG) staining were used to detect the pathological changes of heart and thoracic aorta. Colorimetric analysis was employed to determine serum nitric oxide level (NO), malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity. ELISA was used to detect serum B-type natriuretic peptide (BNP) and serum inflammatory cytokines, as well as endothelial NO synthetase (eNOS), angiotensinII (Ang II) and endothelin-1(ET-1) concentration in both serum and cardiac tissues. Immunohistochemistry and Western blotting (WB) were employed to detect eNOS and inflammatory cytokine expressions in cardiac tissues. RESULTS: XJEK administration markedly ameliorated cardiac dysfunction and abnormal ECG manifested by decreased weight/body weight (HW/BW) ratio, BNP and remedied hypertrophy of cardiomyocytes and deposition of collagen, which might be in part attributed to the increased SOD and decreased MDA in serum. Furthermore, XJEK administration improved ED with boosted eNOS activities in serum and cardiac tissues, as well as up-regulated NO levels in serum, down-regulated Ang II and ET-1 content in serum and cardiac tissues. Lastly, protein expression of pro-inflammation cytokines significantly decreased, and anti-inflammatory cytokine was significantly enhanced in serum and cardiac tissues compared to model group. CONCLUSION: XJEK may exert beneficial effects on HF induced by MI in mice, and the underlying mechanism may be attributable to the amelioration of ED, anti-OS and anti-inflammation effects.
Authors: Jun Chen; Rui Xue; Li Li; Li Li Xiao; Jiahong Shangguan; Wenjing Zhang; Xueyang Bai; Gangqiong Liu; Ling Li Journal: Front Pharmacol Date: 2019-09-20 Impact factor: 5.810
Authors: Arthur José Pontes Oliveira de Almeida; Mathania Silva de Almeida Rezende; Sabine Helena Dantas; Sonaly de Lima Silva; Júlio César Pinheiro Lúcio de Oliveira; Fátima de Lourdes Assunção Araújo de Azevedo; Rayanne Maira Felix Ribeiro Alves; Geovânia Maria Sales de Menezes; Pablo Ferreira Dos Santos; Tays Amanda Felisberto Gonçalves; Valérie B Schini-Kerth; Isac Almeida de Medeiros Journal: Oxid Med Cell Longev Date: 2020-05-08 Impact factor: 6.543