scholarly journals Understanding the Multitarget Pharmacological Mechanism of the Traditional Mongolian Common Herb Pair GuangZao-RouDouKou Acting on Coronary Heart Disease Based on a Bioinformatics Approach

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jingkun Lu ◽  
Yuchong Hu ◽  
Lechun Wang ◽  
Yuewu Wang ◽  
Shengsang Na ◽  
...  

GuangZao and RouDouKou (Fructus Choerospondiatis and Nutmeg, FCN) are one of the most common herb pairs in traditional Mongolian medicine for the treatment of coronary heart disease (CHD). However, evidence for the protective effect of FCN is limited, and its underlying mechanism of action remains unclear. The present study employed a network pharmacology approach to identify the potentially active ingredients and synergistic effects of the herb pair FCN as traditional Mongolian medicine. We predicted the targets of all available FCN ingredients with PharmMapper, SWISS, and SuperPred Server and clustered CHD-related targets from the DrugBank and the OMIM database. We also evaluated the links between herbal ingredients and pharmacological actions to explore the potential mechanism of action of FCN. We found that FCN targets a network of CHD-related key processes, including stress responses, cell adhesion and connections, angiogenesis, cell apoptosis and necrosis, the endocrine system, inflammatory and immune responses, and other biological processes. To confirm the predicted results, we investigated the protective effect of FCN on isoproterenol- (ISO-) induced myocardial ischemia in rats. Pathological assessment indicated that FCN inhibits apoptosis and inflammatory responses involving the myocardium. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analyses demonstrated the therapeutic effects of FCN on ISO-induced myocardial ischemia rats, possibly via regulating stress and inflammatory responses and inhibiting cardiomyocyte apoptosis. The findings of the present study indicate that bioinformatics combined with experimental verification provide a credible and objective method to elucidate the complex multitarget mechanism of action of FCN.

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Bailu Duan ◽  
Lintao Han ◽  
Shuping Ming ◽  
JingJing Li ◽  
Qiong Wang ◽  
...  

The Fuling (Poria cocos)-Guizhi (Cinnamomi ramulus) herb pair (FGHP) is a commonly used traditional Chinese herbal formula with coronary heart disease (CHD) treatment potential. However, the mechanism of FGHP in the treatment of CHD was still unclear. In this study, the action targets and underlying mechanism of FGHP against CHD were successfully achieved by combined network pharmacology prediction with experimental verification. 76 common targets were screened out by overlapping the chemical-protein data of FGHP and CHD-related targets. Then, two key targets were further selected for verification by using western blot analysis after analyzing PPI, GO function, and KEGG pathway. Results indicated FGHP could alleviate CHD syndromes and regulate inflammatory responses in acute myocardial ischemia rats, and the reduction of expression of TNF-α and IL-6 in myocardial tissue would be one of its possible underlying mechanisms. Our work demonstrated that network pharmacology combined with experimental verification provides a credible method to elucidate the pharmacological mechanism of FGHP against CHD.


2016 ◽  
Vol 39 (5) ◽  
pp. 1955-1963 ◽  
Author(s):  
Jianchun Huang ◽  
Xiaojun Tang ◽  
Fangxing Ye ◽  
Junhui He ◽  
Xiaolong Kong

Background/Aims: Coronary heart disease is characterized by vascular stenosis or occlusion resulting in myocardial ischemia, hypoxia and necrosis. In China, the combination of aspirin and Fufang Danshen Diwan (FDD), a traditional Chinese medicine formula, has been suggested in the treatment of coronary heart disease. There have been several studies comparing the effectiveness of aspirin alone and in combination with FDD to treat coronary artery disease; however, it remains unclear whether combined aspirin therapy is superior. This study was thus designed to clarify this issue through a systematic review and meta-analysis. Methods: Databases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) database, Wanfang Data and VIP Information were searched. Papers were reviewed systematically by two researchers and analyzed using Cochrane software Revman 5.1. Results: Fourteen randomized controlled trials enrolling 1367 subjects were included. Meta-analyses revealed that aspirin in combination with FDD was significantly more effective at alleviating angina pectoris and improving electrocardiogram (ECG) results relative to aspirin therapy alone, reflected by the summary effects for the clinical markedly effective (OR = 2.45; 95% CI 1.95-3.08) and the total effective (OR = 3.92; 95% CI 2.87-5.36) rates. In addition, combined aspirin and FDD was significantly more efficacious than aspirin monotherapy at improving blood lipid levels, as indicated by the following outcomes: 1) reduction of TC level (SMD −1.12; 95% CI −1.49 to −0.76); 2) reduction of TG level (SMD −0.94; 95% CI −1.15 to -0.74); 3) reduction of LDL level (SMD -0.68; 95% CI -0.88 to -0.48); and 4) improvement of HDL level (SMD 0.52; 95% CI 0.04 to 0.99 ). No serious adverse events were reported in any of the included trials. Conclusion: The present meta-analysis demonstrated that aspirin in combination with FDD was more effective than aspirin alone for treating coronary heart disease. More full-scale randomized clinical trials with reliable designs are recommended to further evaluate the clinical benefits and long-term effectiveness of FDD for the treatment of coronary heart disease.


2020 ◽  
Author(s):  
Yue-hong Shen ◽  
Shu-lin Wang ◽  
Na Wu ◽  
Yu-chen Dai ◽  
Qian Zhou ◽  
...  

Abstract ObjectiveOur study aimed to investigate the potential mechanisms of the herb pair Zhizi-Danshen (ZD) for coronary heart disease (CHD) using network pharmacological data mining technology.MethodsThe Traditional Chinese Medicine System Pharmacology (TCMSP) database was used to collect the active ingredients of ZD and predict ZD-related target proteins. Afterwards, we identified CHD-related targets from DisGeNET database, NCBI gene database, and TTD database. The common targets both from ZD and CHD were screened by Venny2.1, which were then imported into the String database for protein-protein interaction (PPI) analysis. Finally, the GO and KEGG enrichment analysis were performed by R software, and the network construction was established using Cytoscape3.7.2.ResultsWe obtained 199 possible targets from 62 candidate ingredients of ZD and 1033 CHD-ralated targets, with 83 overlapping common target genes. Then, 11 core targets were acquired from PPI network analysis. Further, GO analysis showed that these common targets mainly influenced receptor ligand activity,cytokine activity,cytokine receptor binding,steroid hormone receptor activity, and peptide binding. KEGG pathway analysis indicated that ZD affected CHD through seven important pathways linked to vascular endothelial function regulation (fluid shear stress and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway), imflammatory effects (IL-17 signaling pathway, TNF signaling pathway,Toll-like receptor signaling pathway),and hormone regulation (relaxin signaling pathway). ConclusionsThis study revealed the potential pharmacological mechanisms of ZD against CHD, which were mainly associated with regulation of vascular endothelial function and inflammatory effects, promotion of vasodilatation, and prevention of cardiac fibrosis. Moreover, it provided a novel conception for the development of alternative therapies on CHD.


2017 ◽  
Author(s):  
Abhiram S. Rao ◽  
Daniel Lindholm ◽  
Manuel A. Rivas ◽  
Joshua W. Knowles ◽  
Stephen B. Montgomery ◽  
...  

AbstractPCSK9 inhibitors are a potent new therapy for hypercholesterolemia and have been shown to decrease risk of coronary heart disease. Although short-term clinical trial results have not demonstrated major adverse effects, long-term data will not be available for some time. Genetic studies in large well-phenotyped biobanks offer a unique opportunity to predict drug effects and provide context for the evaluation of future clinical trial outcomes. We tested association of the PCSK9 loss-of-function variant rsll591147 (R46L) in a hypothesis-driven 11 phenotype set and a hypothesis-generating 278 phenotype set in 337,536 individuals of British ancestry in the United Kingdom Biobank (UKB), with independent discovery (n = 225K) and replication (n = 112K). In addition to the known association with lipid levels (OR 0.63) and coronary heart disease (OR 0.73), the T allele of rs11591147 showed a protective effect on ischemic stroke (OR 0.61, p = 0.002) but not hemorrhagic stroke in the hypothesis-driven screen. We did not observe an association with type 2 diabetes, cataracts, heart failure, atrial fibrillation, and cognitive dysfunction. In the phenome-wide screen, the variant was associated with a reduction in metabolic disorders, ischemic heart disease, coronary artery bypass graft operations, percutaneous coronary interventions and history of angina. A single variant analysis of UKB data using TreeWAS, a Bayesian analysis framework to study genetic associations leveraging phenotype correlations, also showed evidence of association with cerebral infarction and vascular occlusion. This result represents the first genetic evidence in a large cohort for the protective effect of PCSK9 inhibition on ischemic stroke, and corroborates exploratory evidence from clinical trials. PCSK9 inhibition was not associated with variables other than those related to low density lipoprotein cholesterol and atherosclerosis, suggesting that other effects are either small or absent.


2019 ◽  
Vol 3 (6) ◽  
Author(s):  
Shuo Huang

Objective: To compare clinical efficacy of ticagrelor and clopidogrel for treatment of coronary heart disease with myocardial ischemia to provide references for later phase of clinical treatment. Methods: Ninety-six coronary heart disease patients with myocardial ischemia admitted to our hospital from July 20 to July 2019 were recruited as subjects. They were randomly divided into study group and control group according to parity of case number, with 48 patients in each group. Control group was given treatment with clopidogrel, while patients in study group were given treatment with ticagrelor. Clinical efficacy was compared between the both groups. Results: Comparison showed that total effective rate of clinical treatment was higher in study group when compared to control group (P<0.05). Frequency of ST segment depression, duration of ST segment depression, systolic blood pressure, diastolic blood pressure, heart rate and other clinical indicators in study group were superior to control group (P<0.05). Whole blood viscosity at low shear rate, whole blood viscosity at high shear rate, plasma viscosity shear rate, total cholesterol, triglyceride and other haemorheological parameters in study group were superior to control group (P<0.05). Conclusion: Application of ticagrelor has higher clinical efficacy than clopidogreal for coronary heart disease patients with myocardial ischemia. Clinical indicators and haemorheological parameters of myocardial ischemia patients were significantly improved. It should be promoted for application.


Circulation ◽  
1990 ◽  
Vol 81 (6) ◽  
pp. 1792-1802 ◽  
Author(s):  
B Trimarco ◽  
S Chierchia ◽  
G Lembo ◽  
N De Luca ◽  
B Ricciardelli ◽  
...  

2021 ◽  
Vol 14 ◽  
Author(s):  
Chunlai Zhao ◽  
Wenjia Wang ◽  
Kaijing Yan ◽  
He Sun ◽  
Jihong Han ◽  
...  

: The alterations in vascular homeostasis is deeply involved in the development of numerous diseases, such as coronary heart disease, stroke, and diabetic complications. Changes in blood flow and endothelial permeability caused by vascular dysfunction are the common mechanisms for these three types of diseases. The disorders of glucose and lipid metabolism can result in changes of the energy production patterns in endothelium and surrounding cells which may consequently cause local energy metabolic disorders, oxidative stress and inflammatory responses. Traditional Chinese medicine (TCM) follows the principle of the “treatment by the syndrome differentiation”. TCM considers of that coronary heart disease, stroke and diabetes complications all as the type of “Qi deficiency and Blood stasis” syndrome, which mainly happens to the vascular system. Therefore, the common pathogenesis of these three types of diseases suggests the treatment strategy by TCM should be in a close manner and named as “treating different diseases by the same treatment”. Qishen Yiqi dripping pills is a modern Chinese herbal medicine which has been widely used for treatment of patients with coronary heart disease characterized as “Qi deficiency and blood stasis” in China. Recently, many clinical reports have demonstrated the potent therapeutic effects of Qishen Yiqi dripping pills on ischemic stroke and diabetic nephropathy. Based on these reports, we will summarize the clinical applications of Qishen Yiqi dripping pills on coronary heart disease, ischemic stroke and diabetic nephropathy, including the involved mechanisms with basic researches.


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