Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure

Zhu, Min; Zhang, Fugeng; Zhang, Shaoqiang; Du, Wei; Xiao, Xuefeng

doi:10.3389/fphar.2019.01046

Cited by 19 publications

(11 citation statements)

References 70 publications

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“…Modern pharmacological studies have shown that the core active ingredients of QQC, ginsenoside-Rb2, palmitic acid, astragaloside IV, salvianolic acid A, salvianolic acid B, aconitine, hypoaconitine ( Zhang et al, 2019 ), and so forth can treat HF by the following mechanisms. First, QQC can inhibit oxidative stress-induced cardiomyocyte apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Qili Qiangxin Capsule Combined With Sacubitril/Valsartan for HFrEF: A Systematic Review and Meta-Analysis

et al. 2022

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Background: Heart failure with reduced ejection fraction (HFrEF) is a complex, chronic disease and is among the top causes of morbidity and mortality. Angiotensin receptor-neprilysin inhibitor drugs represented by sacubitril/valsartan are the key drugs for the treatment of HFrEF in western medicine, and Qili Qiangxin Capsule (QQC) is a vital drug for the treatment of HFrEF in Chinese medicine. In recent years, there have been many relevant clinical studies on the combination of the two in the treatment of HFrEF. There are no systematic reviews or meta-analyses specific to sacubitril/valsartan combined with QQC for the treatment of HFrEF, so there is an urgent need to evaluate the effectiveness and safety of these two drugs.Objective: To systematically assess the safety and effectiveness of QQC combined with sacubitril/valsartan in the treatment of HFrEF through a meta-analysis.Methods: Searching studies on the combination of QQC and sacubitril/valsartan in the treatment of HFrEF, from databases such as PubMed, Cochrane Library, Web of Science, Wanfang Databases, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure, prior to 31 October 2021. Two reviewers regulated research selection, data extraction, and risk of bias assessment. Review Manager Software 5.4 was used for meta-analysis.Results: There were 26 studies with 2,427 patients included in total. The meta-analysis showed the combination therapy has significant advantages in improving the clinical efficacy, 6-MWT (RR = 1.18, 95% CI: 1.11–1.26, MD = 70.65, 95% CI: 23.92–117.39), superior in ameliorating LVEF, LVEDD, LVESD, and SV (LVEF: MD = 5.41, 95% CI: 4.74–6.08; LVEDD: MD = −4.41, 95% CI: −6.19 to −2.64; LVESD: MD = −3.56, 95% CI: −4.58 to −2.54; and SV: MD = 5.04, 95% CI: 3.67–6.40), and in improving BNP, NT-proBNP, AngII, and ALD (BNP: MD = −97.55, 95% CI: −112.79 to −82.31; NT-proBNP: MD = −277.22, 95% CI: −348.44 to −206.01; AngII: MD = −11.48, 95% CI: −15.21 to −7.76; and ALD: MD = −26.03, 95% CI: −38.91 to −13.15), and all the differences have statistical advantages (p < 0.05). There are no advantages in improving CO and adverse events (MD = 0.66, 95% CI: −0.12 to 1.43 and RR = 0.62, 95% CI: 0.37–1.04, respectively), and the differences have no statistical advantages.Conclusion: Compared with the control group, QQC combined with sacubitril/valsartan may be effective in the treatment of HFrEF. However, the conclusion of this study must be interpreted carefully due to the high risk and ambiguity of bias in the included trials.

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Section: Discussionmentioning

confidence: 99%

Qili Qiangxin Capsule Combined With Sacubitril/Valsartan for HFrEF: A Systematic Review and Meta-Analysis

et al. 2022

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“…Subsequently, network pharmacology analysis of YYH, DZ, BGZ, and TSZ was done to determine the possible functional chemical compounds and potential targets. Considering that certain chemical compounds lacking appropriate pharmacokinetics properties cannot bind effectively to the target or produce pharmacological effects, refer to the previous study ( Guo et al, 2019 ; Liu et al, 2020 ; Zhang et al, 2019 ), OB ≥ 30% and DL ≥ 0.18 were viewed as pharmacokinetically effective to be absorbed and utilized by oral administration in this study.…”

Section: Discussionmentioning

confidence: 99%

“…The characteristic of network pharmacology is following the holistic theory of TCM(S. He et al, 2019b ). The basic opinion of network pharmacology is well suited for exploring the mechanisms of multi-components and multi-targets drugs, so it is an ideal approach in investigating and identifying the mechanism of the TCM formula ( Guo et al, 2019 ; Huang et al, 2020 ; Liu et al, 2020 ; Zhang et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Integrated Strategy of Network Pharmacological Prediction and Experimental Validation Elucidate Possible Mechanism of Bu-Yang Herbs in Treating Postmenopausal Osteoporosis via ESR1

et al. 2021

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Postmenopausal osteoporosis (PMOP) is a type of bone metabolism disease-related to estrogen deficiency with an increasing incidence. Traditional Chinese (TCM) has always been used and showed effectiveness in treating PMOP. In the current study, Bu-Yang herbs were considered to be the most frequently used and efficient TCM herbs in PMOP treatment. However, chemical and pharmacological profiles were not elucidated. Network pharmacology was conducted on representative Bu-Yang herbs (Yin-Yang-Huo. Du-Zhong, Bu-Gu-Zhi, Tu-Si-Zi) to investigate the mechanism of Bu-Yang herbs on PMOP. Chemical compounds, potential targets, and disease related genes were available from the corresponding database. Results showed that Bu-Yang herbs could interact with ESR1 and estrogen signaling pathways. For further validation, the Bu-Yang decoction (BYD), formula consisted of the above-mentioned 4 Bu-Yang herbs was presented for experimental validation. In vivo, BYD significantly reversed ovariectomy (OVX)-induced osteoporosis progress in a dose-dependent manner by up-regulation of bone mineral density and amelioration of bone microarchitecture. In vitro, BYD dramatically improved the proliferation and mineral nodules formation of osteoblasts. Both in vitro and in vivo results illustrated that the phenotype change induced by BYD is correlated with up-regulated of ESR1 and activation of the β-catenin pathway. Meanwhile, inhibition of ESR1 by ICI182, 780 blocked the osteogenic phenotype and β-catenin pathway activation induced by BYD. In conclusion, the current study suggested that Bu-Yang herbs are the most useful TCM herbs in treating PMOP. Furthermore, the integrated strategy of network pharmacology prediction with experimental validation suggested that BYD exerted its anti-PMOP via ESR1 and the downstream mechanism might be activation of the β-catenin signaling pathway.

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“…QLQX has been proven to have a great potential as a promising metabolic modulator as it can regulate cardiac glucose and FA metabolism simultaneously by upregulating a large number of enzymes, including GLUT4, GLUT1, CD36, and so forth in different pathological models ( Shen et al, 2017 ; Wang et al, 2017 , 2018 ). This multi-targeting regulation might depend on the multiple components identified in QLQX, encompassing ginsenoside Rb1, astragaloside, salvianolic acid A, and so forth ( Zhang et al, 2019 ). Most of these components have demonstrated an ability to target energy metabolism ( Dong et al, 2017 ; Zheng et al, 2017 ; Cui et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Qiliqiangxin capsules (QLQX), a listed traditional Chinese medicine comprising 11 herbs, were approved by the China Food and Drug Administration in 2004. Its main components include Astragali Radix, Ginseng Radix et Rhizoma, Aconiti Lateralis Radix Preparata, Salvia Miltiorrhiza Radix et Rhizoma, Alismatis Rhizoma, Descuraunia Semen, Cinnamomi Ramulus, Carthami Flos, Periplocae Cortex, Polygonati Odorati Rhizoma, and Citri Reticulatae Pericarpium (Li et al, 2013;Zhang et al, 2019). The favorable efficacy of QLQX in HF therapy has been confirmed by a multicentral large-scale clinical trial (Li et al, 2013;Tang and Huang, 2013) and several lab experiments (Tao et al, 2015;Liang et al, 2016;Han et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Qiliqiangxin Capsules Optimize Cardiac Metabolism Flexibility in Rats With Heart Failure After Myocardial Infarction

et al. 2020

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Metabolic modulation is a promising therapy for ischemic heart disease and heart failure. This study aimed to clarify the regional modulatory effect of Qiliqiangxin capsules (QLQX), a traditional Chinese medicine, on cardiac metabolic phenotypes. Sprague-Dawley rats underwent left anterior descending coronary artery ligation and were treated with QLQX and enalapril. Striking global left ventricular dysfunction and left ventricular remodeling were significantly improved by QLQX. In addition to the posterior wall, QLQX also had a unique beneficial effect on the anterior wall subject to a severe oxygen deficit. Cardiac tissues in the border and remote areas were separated for detection. QLQX enhanced the cardiac 18 F-fluorodeoxyglucose uptake and the levels and translocation of glucose transport 4 (GLUT4) in the border area. Meanwhile, it also suppressed glucose transport 1 (GLUT1) in both areas, indicating that QLQX encouraged border myocytes to use more glucose in a GLUT4-dependent manner. It was inferred that QLQX promoted a shift from glucose oxidation to anaerobic glycolysis in the border area by the augmentation of phosphorylated pyruvate dehydrogenase, pyruvate dehydrogenase kinases 4, and lactic dehydrogenase A. QLQX also upregulated the protein expression of fatty acid translocase and carnitine palmitoyl transferase-1 in the remote area to possibly normalize fatty acid (FA) uptake and oxidation similar to that in healthy hearts. QLQX protected global viable cardiomyocytes and promoted metabolic flexibility by modulating metabolic proteins regionally, indicating its potential for driving the border myocardium into an anaerobic glycolytic pathway against hypoxia injuries and urging the remote myocardium to oxidize FA to maximize energy production.

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Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure

Cited by 19 publications

References 70 publications

Qili Qiangxin Capsule Combined With Sacubitril/Valsartan for HFrEF: A Systematic Review and Meta-Analysis

Qili Qiangxin Capsule Combined With Sacubitril/Valsartan for HFrEF: A Systematic Review and Meta-Analysis

Integrated Strategy of Network Pharmacological Prediction and Experimental Validation Elucidate Possible Mechanism of Bu-Yang Herbs in Treating Postmenopausal Osteoporosis via ESR1

Qiliqiangxin Capsules Optimize Cardiac Metabolism Flexibility in Rats With Heart Failure After Myocardial Infarction

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