Ruifeng Bai1, Xu Yin2, Xiao Feng3, Yuan Cao4, Yan Wu5, Zhixiang Zhu6, Chun Li7, Pengfei Tu8, Xingyun Chai9. 1. Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: raylawhite@163.com. 2. Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: xuyinvip@163.com. 3. Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: fengxiao931209@163.com. 4. Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: caoyuan0512@163.com. 5. Research Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: nayattmm@vip.sina.com. 6. Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: ahssfxgt@163.com. 7. Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: lichun19850204@163.com. 8. Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: pengfeitu@vip.163.com. 9. Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: xingyunchai@yeah.net.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis hendersonii Hemsl. (CH) with heat clearing and detoxifying effects are well described in Tibetan folk medicine. It has been used for centuries in China largely for the treatment of high altitude polycythemia, a pathophysiological condition referred to "plethora" in Tibetan medicine, hypertension, hepatitis, edema, gastritis, and other infectious diseases. AIM OF THE STUDY: To investigate the cardioprotective effects of Corydalis hendersonii extract in an ICR mouse model of myocardial ischemic injury. MATERIALS AND METHODS: Ethanol [85% (v/v)] extract of CH whole plant was prepared, and their chemical profile was analyzed with use of HPLC-DAD and IT-TOF-ESI-MS. A mouse model of AMI was established by ligation of the left ventricular dysfunction (LAD) coronary artery. Mice were randomly divided into six groups (n = 12 per group): sham group, model group, CH groups treated with three doses of CH (100, 200, and 400mg/kg, intragastric), and a positive control group (captopril, 16.67mg/kg, intragastric). Heart function was evaluated by measurement of ejection fraction (EF) and fractional shortening (FS) by echocardiography. Serum levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), plasma levels of angiotensin II (AngII), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the cardiac tissue homogenate, protein expressions of signal-transduction proteins, p65, IκBα, JAK2, and STAT3 in heart tissues were measured by ELISA and Western blot analyses. Inflammatory cell infiltration and changes in collagen deposition in the myocardial ischemic heart tissues were observed by histopathological examination. Platelet aggregation in vitro was also assessed. RESULTS: CH treatment showed a dose-dependent cardioprotective effect. It significantly reduced left ventricular end-diastolic diameter (LVEDd) and left ventricular end-diastolic diameter (LVEDs), improved EF and FS as compared to those in the model group; attenuated the increase levels of CK-MB and LDH in serum; reduced expressions of AngII, TNF-α, IL-6 and IL-1ß in plasma, MMP-2 and MMP-9 expressions in the cardiac tissue homogenate; and down-regulated myocardial expressions of p-p65, p-IκBα, p-JAK2, p-STAT3, MMP-2, and MMP-9 in AMI mice. Also, an obvious reduction in inflammatory cell infiltration in the myocardial infarct was found in all CH treated groups. Besides, CH also inhibited platelet aggregation induced by THR, ADP, and AA. CONCLUSION: CH extract exerted a protective effect against myocardial ischemic injury via inhibition of inflammation, myocardial fibrosis, and platelet aggregation. This study demonstrates such protection for the first time and provides a basis for development of CH-based drugs for treatment of ischemic heart disease in clinical settings.
ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis hendersonii Hemsl. (CH) with heat clearing and detoxifying effects are well described in Tibetan folk medicine. It has been used for centuries in China largely for the treatment of high altitude polycythemia, a pathophysiological condition referred to "plethora" in Tibetan medicine, hypertension, hepatitis, edema, gastritis, and other infectious diseases. AIM OF THE STUDY: To investigate the cardioprotective effects of Corydalis hendersonii extract in an ICR mouse model of myocardial ischemic injury. MATERIALS AND METHODS:Ethanol [85% (v/v)] extract of CH whole plant was prepared, and their chemical profile was analyzed with use of HPLC-DAD and IT-TOF-ESI-MS. A mouse model of AMI was established by ligation of the left ventricular dysfunction (LAD) coronary artery. Mice were randomly divided into six groups (n = 12 per group): sham group, model group, CH groups treated with three doses of CH (100, 200, and 400mg/kg, intragastric), and a positive control group (captopril, 16.67mg/kg, intragastric). Heart function was evaluated by measurement of ejection fraction (EF) and fractional shortening (FS) by echocardiography. Serum levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), plasma levels of angiotensin II (AngII), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the cardiac tissue homogenate, protein expressions of signal-transduction proteins, p65, IκBα, JAK2, and STAT3 in heart tissues were measured by ELISA and Western blot analyses. Inflammatory cell infiltration and changes in collagen deposition in the myocardial ischemic heart tissues were observed by histopathological examination. Platelet aggregation in vitro was also assessed. RESULTS: CH treatment showed a dose-dependent cardioprotective effect. It significantly reduced left ventricular end-diastolic diameter (LVEDd) and left ventricular end-diastolic diameter (LVEDs), improved EF and FS as compared to those in the model group; attenuated the increase levels of CK-MB and LDH in serum; reduced expressions of AngII, TNF-α, IL-6 and IL-1ß in plasma, MMP-2 and MMP-9 expressions in the cardiac tissue homogenate; and down-regulated myocardial expressions of p-p65, p-IκBα, p-JAK2, p-STAT3, MMP-2, and MMP-9 in AMI mice. Also, an obvious reduction in inflammatory cell infiltration in the myocardial infarct was found in all CH treated groups. Besides, CH also inhibited platelet aggregation induced by THR, ADP, and AA. CONCLUSION: CH extract exerted a protective effect against myocardial ischemic injury via inhibition of inflammation, myocardial fibrosis, and platelet aggregation. This study demonstrates such protection for the first time and provides a basis for development of CH-based drugs for treatment of ischemic heart disease in clinical settings.
Authors: Ji Hye Han; Jung Heun Ju; Yong Sun Lee; Ju Ho Park; In Jun Yeo; Mi Hee Park; Yoon Seok Roh; Sang Bae Han; Jin Tae Hong Journal: Sci Rep Date: 2018-09-20 Impact factor: 4.379