danhong injection
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2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Shuang He ◽  
Rongrong Chen ◽  
Li Peng ◽  
Zhenzuo Jiang ◽  
Haixin Liu ◽  
...  

Abstract Objective We investigate the chemical basis and mechanism of angiogenesis regulation by a multicomponent Chinese medicine Danhong injection (DHI). Methods DHI was fractionated and screened for angiogenesis activities by in vitro tube formation and migration assays. The composition of DHI components was determined by UPLC. The effects of the main active monomers on angiogenesis-related gene and protein expression in endothelial cells were determined by qPCR and Western blotting analyses. Mouse hind limb ischemia and tumor implant models were used to verify the angiogenesis effects in vivo by Laser Doppler and bioluminescent imaging, respectively. Results Two distinct chemical components, one promoting (pro-angiogenic, PAC) and the other inhibiting (anti-angiogenic, AAC) angiogenesis, were identified in DHI. PAC enhanced angiogenesis and improved recovery of ischemic limb perfusion while AAC reduced Lewis lung carcinoma growth in vivo in VEGFR-2-Luc mice. Among the PAC or AAC monomers, caffeic acid and rosmarinic acid upregulated TSP1 expression and downregulated KDR and PECAM expression. Caffeic acid and rosmarinic acid significantly decreased while protocatechuic aldehyde increased CXCR4 expression, which are consistent with their differential effects on EC migration. Conclusions DHI is capable of bi-directional regulation of angiogenesis in disease-specific manner. The pro-angiogenesis activity of DHI promotes the repair of ischemic vascular injury, whereas the anti-angiogenesis activity inhibits tumor growth. The active pro- and anti-angiogenesis activities are composed of unique chemical combinations that differentially regulate angiogenesis-related gene networks.


Medicine ◽  
2021 ◽  
Vol 100 (46) ◽  
pp. e27683
Author(s):  
Junfeng Gao ◽  
Xiangzhong Shao ◽  
YiXiang Guan ◽  
Juxiang Mei

2021 ◽  
Author(s):  
Shuang He ◽  
Rongrong Chen ◽  
Li Peng ◽  
Zhenzuo Jiang ◽  
Haixin Liu ◽  
...  

Abstract Objective: We aimed to investigate the chemical basis and mechanism of angiogenesis regulation by a multicomponent Chinese medicine Danhong injection (DHI). Methods: A chemical fraction library of DHI was screened and validated for angiogenesis activities by tube formation and migration assays. Mouse ischemic and tumor vascular models were used to verify the angiogenesis effects in vivo. Migration ability of the main monomers of proangiogenic component (PAC) and antiangiogenic component (AAC) in EA.hy926 cells were determined by migration assay. qPCR analyses were performed to access whether the main monomers of PAC or AAC could affect the expression of angiogenesis-related genes in ECs. Western blotting was used to verify the main monomers PAC and AAC effects on CXCR4 protein expression. Results: Two chemically-distinct fractions, including promotion and inhibition of angiogenesis, were identified in DHI. PAC enhanced angiogenesis and improved recovery of ischemic limb perfusion while AAC reduced Lewis lung tumor growth in vivo in VEGFR-2-Luc mice. CA and RA upregulated the expression of TSP1 and downregulated the expression of KDR and PECAM genes. CXCR4 expression was significantly decreased by CA and RA, but increased by PAI, consistent with their differential effects on EC migration. Conclusion: DHI is capable of bi-directional regulation of angiogenesis in a disease-specific manner. The proangiogenesis activity of DHI promotes ischemic vascular injury repair, whereas the anti-angiogenesis activity inhibits tumor growth. The best pro- and anti-angiogenesis activities are composed of unique chemical combinations that differentially regulate angiogenesis-related gene network.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Liu ◽  
Dan-Dan Li ◽  
Wei Dong ◽  
Yu-Qi Liu ◽  
Yang Wu ◽  
...  

AbstractIt’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).


2021 ◽  
Author(s):  
hairong cai ◽  
Luo Sicong ◽  
Gao Huanjia ◽  
Liu Shuling ◽  
Zhao Shuai ◽  
...  

Abstract Background: Acute coronary syndrome (ACS) is a group of clinical syndromes caused by thrombosis caused by rupture of coronary atherosclerotic plaque or erosion ulcer, resulting in complete or incomplete occlusion of blood vessels. ACS is the most common cardiovascular critical disease. Although with the development of coronary intervention technology, the incidence of major adverse cardiovascular events (MACE) is still high. In China, traditional Chinese medicine (TCM) has been widely used in the adjuvant treatment of ACS to improve the symptoms and prognosis. Danhong injection (DHI) and Naoxintong capsule (NXTC) may improve the prognosis of patients with ACS, but the evidence-based evidence is still insufficient. The main purpose of this study was to evaluate the efficacy and safety of DHI combined with NXTC in the treatment of ACS.Methods/design:This is a randomized, placebo-controlled clinical trial.1752 patients with ACS undergoing percutaneous coronary intervention (PCI) will be randomly assigned to receive DHI combined with NXTC or placebo at the ratio of 1:1. The course of treatment was 12 weeks. All participants received conventional treatment. The main outcome measure was the 12-months incidence of MACEs. Adverse events (AE) will also be evaluated.Discussion:This trial is a well designed study according to principles and regulations issued by the China food and Drug Administration (CFDA). The results will provide high-quality evidence for the efficacy and safety of DHI combined with NXTC in the treatment of ACS. The results of this study can provide clinicians with evidence-based recommendations for treatment of ACS.Trial registration:Chinese Clinical Trial Registry(http://www.chictr.org.cn/index.aspx), ChiCTR-IOR-14005693.Registered on November 12,2014.


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