Integrating network analysis and experimental validation to reveal the mitophagy-associated mechanism of Yiqi Huoxue (YQHX) prescription in the treatment of myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion (I/R) injury is the main cause of increasing postischemic heart failure and currently there is no definite treatment for myocardial I/R injury. It has been suggested that oxidative stress-induced mitochondrial dysfunction plays an important role in the pathological development of myocardial I/R. In this study, Yiqi Huoxue (YQHX) prescription, as a kind of Chinese herbal formula, was developed and shown to alleviate I/R injury. Network analysis combined with ultrahigh-performance liquid chromatography-high resolution mass spectrometry expounded the active components of YQHX and revealed the mitophagy-regulation mechanism of YQHX treating I/R injury. In vivo experiments confirmed YQHX significantly alleviated I/R myocardial injury and relieved oxidative stress. In vitro experiments validated that YQHX could relieve hypoxia/reoxygenation injury and attenuate oxidative stress via improving the structure and function of mitochondria, which was strongly related to regulating mitophagy. In summary, this study demonstrated that YQHX, which could alleviate I/R injury via targeting mitophagy, might be a potential therapeutic strategy for myocardial I/R injury.

Effects of Xinkeshu tablets on coronary heart disease patients combined with anxiety and depression symptoms after percutaneous coronary intervention: A meta-analysis.

BACKGROUND: Xinkeshu tablets (XKS), a well-known Chinese patent drug, have been administered to coronary heart disease (CHD) patients with anxiety and depression after percutaneous coronary intervention (PCI). PURPOSE: This meta-analysis aimed to systematically evaluate the clinical effects of XKS for treating CHD patients with anxiety and depression after PCI. METHODS: Randomized controlled trials (RCTs) about XKS alone or combined with conventional drugs for the treatment of CHD patients with anxiety and depression after PCI were retrieved from 7 databases (MEDLINE, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP) Database, Chinese Biomedical Database (CBM) and Wanfang Database) through November 2021. First, the studies were reviewed and screened by two independent assessors according to the eligibility criteria. Second, the methodological quality of the eligible studies was evaluated based on the Cochrane Collaboration's tool for assessing the risk of bias. Subsequently, meta-analysis was performed by using RevMan 5.4 software, and publication bias was evaluated by Stata 12.0 software. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the quality of the evidence. RESULTS: In total, 11 clinical RCTs involving 1000 patients were included in this study. This meta-analysis found that compared with conventional treatment alone, XKS combined with conventional treatment significantly improved the anxiety scale scores (SMD = -1.97, 95% CI -3.13 to -0.82; p = 0.0008; I2 = 98%), the depression scores (SMD = -2.80, 95% CI -4.49 to -1.10; p = 0.001; I2 = 98%), the scores on the Medical Outcomes Study 36 Item Short Form Health Survey (SF36) (MD = 11.22, 95% CI 4.19 to 18.26; p =0.002; I2 = 95%) and the blood lipid levels of total cholesterol (TC) (MD = -0.38, 95% CI -0.62 to -0.13; p = 0.003; I2 = 0%) and triglyceride (TG) (MD = -0.31, 95% CI -0.46 to -0.17; p < 0.0001; I2 =  0%). CONCLUSION: The current evidence suggests that XKS might benefit CHD patients experiencing anxiety and depression after PCI by helping to improve their depression symptoms, TC and TG blood lipid levels. However, due to insufficient methodological quality of the studies, several risks of bias and inadequate reporting of the clinical data, more rigorous, multicenter, sufficient-sample and double-blind randomized clinical trials are warranted.

Effectiveness and safety of Shugan Jianpi (SGJP) formula in the treatment of nonalcoholic steatohepatitis (NASH): A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: It is known that nonalcoholic steatohepatitis (NASH) has been more and more popular in clinical practice. Apart from lifestyle modification, pharmacological therapy treating NASH has still been limited and insufficient. A growing number of studies demonstrated that Shugan Jianpi (SGJP) formula, as a kind of Chinese herbal medicine prescription, could improve blood lipid indexes, liver function, and other clinical measures in NASH patients. Nevertheless, there still has been a lack of study to systematically assess the efficacy and safety of SGJP formula treating NASH. Therefore, it is necessary to conduct this systematic review and meta-analysis. METHODS: A systematic literature search for articles up to December 2021 will be performed in following electronic databases: MEDLINE, Embase, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database Database, Chinese Biomedical Database, Chinese Biomedical Literature Service System, and Wanfang Database. Inclusion criteria are randomized controlled trials of SGJP formula applied on NASH patients. The primary outcome measures will be liver function, blood lipid indexes, ultrasound, or radiological imaging examination. The safety outcome measures will be adverse events and kidney function. RevMan 5.3 software will be used for data synthesis, sensitivity analysis, subgroup analysis, and risk of bias assessment. A funnel plot will be developed to evaluate reporting bias. Stata 12.0 will be used for meta-regression and Egger tests. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence.Discussion: This study will provide a high-quality synthesis of the efficacy and safety of SGJP for NASH patients. ETHICS AND DISSEMINATION: This systematic review does not require ethics approval and will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: PROSPERO CRD42021259097.

Effectiveness and safety of Xinkeshu on coronary artery disease patients combined with anxiety and depression symptoms after percutaneous coronary intervention: A protocol for systematic review and meta-analysis.

BACKGROUND: It's known that coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI) was significantly associated with anxiety and depression symptoms. Several studies have showed that Xinkeshu tablet (XKS), a kind of Chinese herbal medicine, could effectively improve post-PCI postoperative mood disorders in CHD patients. However, the intensity of evidence has been poor, limiting the further clinical application of XKS to patients above. This systematic review and meta-analysis will assess the effectiveness and safety of studies of XKS in CHD patients with anxiety and depression symptoms after PCI. METHODS: A systematic literature search for articles up to December 2021 will be performed in following electronic databases: PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database Database, Chinese Biomedical Database, Chinese Biomedical Literature Service System, and Wanfang Database. Inclusion criteria are randomized controlled trials of XKS applied on patients with CHD and depression. The primary outcome measures will be CHD-related clinical evaluation (frequency of acute attack angina, severity of angina pectoris, electrocardiographic changes, amount of nitroglycerin) and the scores or reducing fractions of depressive and anxiety measuring scales (the Hospital Anxiety/Depression Scale or other widely used anxiety/depression scale). The safety outcome measures will be adverse events, liver and kidney function. RevMan 5.3 software will be used for data synthesis, sensitivity analysis, subgroup analysis, and risk of bias assessment. A funnel plot will be developed to evaluate reporting bias. Stata 12.0 will be used for meta-regression and Egger tests. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence. DISCUSSION: This study will provide a high-quality synthesis of the effects and safety of XKS for CHD patients with anxiety and depression symptoms after PCI. ETHICS AND DISSEMINATION: This systematic review does not require ethics approval and will be submitted to a peer-reviewed journal.Trial registration number PROSPERO CRD42019131346.

Investigating the mechanisms of Modified Xiaoyaosan (tiaogan-liqi prescription) in suppressing the progression of atherosclerosis, by means of integrative pharmacology and experimental validation.

Atherosclerosis (AS)-related diseases remain among the leading causes of death worldwide. Modified Xiaoyaosan (also called Tiaogan-Liqi prescription, TGLQ), a traditional Chinese medical formulation, has been widely applied in the treatment of AS-related diseases. The aim of this study was to investigate the underlying pharmacological mechanisms of TGLQ in acting on AS. A total of 548 chemical compounds contained in TGLQ, and 969 putative targets, were collected from the Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine, while 1005 therapeutic targets for the treatment of AS were obtained from the DisGeNET, TTD and CTD databases. Moreover, the 63 key targets were screened by the intersection of the targets above, and by network topological analysis. Further functional enrichment analysis showed that the key targets were significantly associated with regulation of the immune system and inflammation, improvement of lipid and glucose metabolism, regulation of the neuroendocrine system and anti-thrombosis effect. The in vivo experiments confirmed that TGLQ could reduce plasma lipid profiles and plasma inflammatory cytokines, and also inhibit AS plaque formation, within the AS model ApoE-/- mice. The in vitro experiments validated the hypothesis that TGLQ could significantly reduce intracellular lipid accumulation, suppress the production of inflammatory cytokines of macrophages induced by oxidized-LDL, and inhibit the protein expression of heat shock protein 90 and toll-like receptor 4. This study identified a list of key targets of TGLQ in the treatment of AS by applying an integrative pharmacology approach, which was validated by in vivo and in vitro experimentation.

Xiaoyaosan (Tiaogan-Liqi therapy) protects peritoneal macrophages from corticosterone-induced stress by regulating the interaction between glucocorticoid receptor and ABCA1.

BACKGROUND: Previous studies have reported that Xiaoyaosan (XYS), Tiaogan-Liqi therapy, has a protective function in depressive disorder, and can regulate body weight and corticosterone (CORT) level. However, little is known about the effect of XYS in treating atherosclerosis. This study aimed to explore the influence XYS on macrophage foam cell formation and related mechanism. METHODS: Rat peritoneal macrophages (PMs) were separated and stimulated with CORT and oxidized low density lipoprotein (ox-LDL). The serum was obtained from rats treated with different doses of XYS and was added into the medium for macrophages. Then, the cell activity and lipid content of PMs were measured through Cell Counting Kit-8 (CCK-8) assay and oil red staining, respectively. The expressions of glucocorticoid receptor (GR), ATP binding cassette subfamily A member 1 (ABCA1), and heat shock protein 90 (HSP90) were detected. In addition, overexpression of GR and ABCA1 was performed and the effect on XYS treatment was subsequently assessed. RESULTS: The CCK-8 assay showed the serum increased cell activity of CORT-induced stress PMs in a XYS dose-dependent manner. Oil red staining and enzyme-linked immunosorbent assay (ELISA) showed that the serum decreased lipids of PMs. In the XYS treated groups, HSP90 protein was decreased and protein levels of ABCA1 and GR were increased in cytoplasm, while GR protein in nucleus was decreased. Co-immunoprecipitation (Co-IP) assay indicated GR might interact with HSP90 and be involved with the function of XYS. Furthermore, overexpression of GR attenuated the protective function of XYS on CORT-induced stress in PMs, while overexpression of ABCA1 enhanced that. CONCLUSIONS: This study denoted that XYS could protect PMs from CORT-induced stress by regulating the interaction of GR and ABCA1, which might contribute to the treatment of atherosclerosis.

Effectiveness and safety of Baduanjin exercise (BDJE) on heart failure with preserved left ventricular ejection fraction (HFpEF): A protocol for systematic review and meta-analysis.

BACKGROUND: Nearly half of the heart failure (HF) patients have been classified as HF with preserved left ventricular ejection fraction (HFpEF) and the prevalence has been increasing over time. The subject of this study is to assess the clinical effectiveness and safety of Baduanjin exercise (BDJE), as a kind of traditional Chinese exercises, for HFpEF patients. METHODS: A systematic literature search for articles up to September 2020 will be performed in following electronic databases: PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP) Database, Chinese Biomedical Database (CBM), Chinese Biomedical Literature Service System (SinoMed) and Wanfang Database. Inclusion criteria are randomized controlled trials of BDJE applied on HFpEF patients. The primary outcome measures will be exercise capacity (cardiopulmonary exercise test or 6-minute walking test) and quality of life. The secondary outcomes will be as the following: blood pressure, heart rate, echocardiography, endothelial function, arterial stiffness and hypersensitive C-reactive protein and N-Terminal pro-B-type natriuretic peptide. The safety outcome measures will be adverse events, liver and kidney function. RevMan 5.3 software will be used for data synthesis, sensitivity analysis, subgroup analysis and risk of bias assessment. A funnel plot will be developed to evaluate reporting bias. Stata 12.0 will be used for meta-regression and Egger tests. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of evidence. CONCLUSION: The study will give an explicit evidence to evaluate the effectiveness and safety of BDJE for HFpEF patients. ETHICS AND DISSEMINATION: This systematic review does not require ethics approval and will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: PROSPERO CRD42020200324.

Efficacy and safety of Zhibitai in treating coronary heart disease patients with hyperlipemia: A protocol for systematic review and meta-analysis.

OBJECTIVE: To assess the clinical efficacy and safety of Zhibitai, as a kind of natural lipid-lowering Chinese medicine, in treating coronary heart disease patients with hyperlipemia METHODS: : A systematic literature search for articles up to July 2020 will be performed in following electronic databases: PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database Database, Chinese Biomedical Database, Chinese Biomedical Literature Service System, and Wanfang Database. Inclusion criteria are randomized controlled trials of Zhibitai applied on coronary heart disease patients with hyperlipemia. The primary outcome measures will be serum lipid levels (including total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and acute cardiovascular events. The secondary outcome measures will be inflammatory factors (high sensitive C-reactive protein, interleukin-6, etc), safety index (liver function, renal function, etc), and adverse events. RevMan 5.3 software will be used for data synthesis, sensitivity analysis, meta-regression, subgroup analysis, and risk of bias assessment. A funnel plot will be developed to evaluate reporting bias and Egger tests will be used to assess funnel plot symmetries. We will use the grading of recommendations assessment, development, and evaluation system to assess the quality of evidence.Trial registration number PROSPERO CRD42018103341.