Zhilong Huoxue Tongyu capsule inhibits rabbit model of hyperlipidemia and atherosclerosis through NF-κB/NLRP3 signaling pathway.

Objective: Zhilong Huoxue Tongyu capsule (ZL) is a Chinese patent medicine for treating cardio-cerebral diseases. However, the pharmacological mechanism by which it regulates blood lipids and treats atherosclerosis (AS) is unclear. Therefore, the purpose of this study is to explore the mechanism of ZL inhibiting hyperlipidemia and treating AS through NF-κB/NLRP3 signaling pathway. Methods: Fifty New Zealand white rabbits were divided into control, model, model + ZL (3.12 g/kg/d, i.g.), model + atorvastatin (0.51 mg/kg/d, i.g.), and model + ZL + atorvastatin groups. Except for the control group, all other groups underwent carotid intima air drying and received a high-fat diet for 28 days to establish hyperlipidemia AS model, and drug treatment was given for the same period of time after modeling. Pathological changes and blood lipids were detected, NF-κB/NLRP3-related protein or gene expression levels were analyzed in carotid tissue. Results: ZL significantly reduced blood lipids and delayed the progression of AS. TC, TG, and LDL-C were decreased while HDL-C was increased in blood, IMT thickening and plaque formation of carotid arteries were inhibited, VRI was alleviated, and pathological features were improved. NF-κB, NLRP3 and IL-1ß in the carotid artery were significantly down-regulated after intervention with ZL. RT-PCR and western blot analysis showed that NF-κB (p-NF-κB), NLRP3, caspase-1, IL-1ß and IL-18 were significantly downregulated by ZL. Conclusions: ZL can be used effectively as adjuvant therapy for hyperlipidemia and AS, combining it with atorvastatin yielded more optimized efficacy, but its anti-inflammatory and pharmacological mechanisms of inhibiting pyroptosis should be studied further.

A classical herbal formula alleviates high-fat diet induced nonalcoholic steatohepatitis (NASH) via targeting mitophagy to rehabilitate dysfunctional mitochondria, validated by UPLC-HRMS identification combined with in vivo experiment.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) has caused a significant burden on public health care systems, the economy and society. However, there has still been no officially approved pharmacotherapy for NASH. It has been suggested that oxidative stress and mitochondrial dysfunction play vital roles in NASH pathological progression. Shugan Xiaozhi (SG) formula, as a kind of classical herbal formula, was shown to attenuate NASH. PURPOSE: This study aimed to explore the potential mechanisms of SG formula treating NASH. STUDY DESIGN AND METHODS: Ultra-high-performance liquid chromatography-high resolution mass spectrometry combined with bioinformatics analysis was applied to explore the therapeutic targets and main components of SG formula. Moreover, in vivo NASH model was utilized to confirmed the therapeutic effects of SG formula. Molecular docking analysis and further validation experiments were conducted to verify the results of bioinformatics analysis. RESULTS: The in vivo experiments confirmed SG formula significantly attenuated hepatic pathological progression and relieved oxidative stress in high-fat diet (HFD) induced - NASH model. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) combined with bioinformatics analysis expounded the components of SG formula and revealed the mitochondrial regulation mechanism of SG formula treating NASH. Further in vivo experiments validated that SG formula could alleviate oxidative stress by rehabilitating the structure and function of mitochondria, which was strongly related to regulating mitophagy. CONCLUSION: In summary, this study demonstrated that SG formula, which could attenuate NASH by regulating mitochondria and might be a potential pharmacotherapy for NASH.

Iristectorigenin C suppresses LPS-induced macrophages activation by regulating mPGES-1 expression and p38/JNK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used clinically to treat inflammatory diseases clinically. However, the adverse effects of NSAIDs cannot be ignored. Therefore, it is critical for us to find alternative anti-inflammatory drugs that can reduce adverse reactions to herbal medicine, such as Iris tectorum Maxim., which has therapeutic effects and can treat inflammatory diseases and liver-related diseases. AIM OF THE STUDY: This study aimed to isolate active compounds from I. tectorum and investigate their anti-inflammatory effects and action mechanisms. MATERIALS AND METHODS: Fourteen compounds were isolated from I. tectorum using silica gel column chromatography, Sephadex LH-20, ODS and high performance liquid chromatography, and their structures were identified by examining physicochemical properties, ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Classical inflammatory cell models were established using lipopolysaccharide (LPS)-stimulated RAW264.7 cells and rat primary peritoneal macrophages to examine the effect of these compounds. To examine the action mechanisms, the nitric oxide (NO) levels were measured by Griess reagent and the levels of inflammatory cytokines in the supernatant were measured by ELISA; The expressions of major proteins in prostaglandin E2 (PGE2) synthesis and the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were examined by Western blotting, and the mRNA expression levels were measured by quantitative real-time polymerase chain reaction; and the nuclear translocation of p65 was examined by high content imaging. Molecular docking was used to predict the binding of active compound to target protein. RESULTS: Our findings revealed that Iristectorigenin C (IT24) significantly inhibited the levels of NO and PGE2 without affecting cyclooxygenase (COX)-1/COX-2 expression in LPS-induced RAW264.7 cells and rat peritoneal macrophages. Furthermore, IT24 was shown to decrease the expression of microsomal prostaglandin synthetase-1 (mPGES-1) in LPS-induced rat peritoneal macrophages. IT24 did not suppress the phosphorylation and nuclear translocation of proteins in the NF-κB pathway, but it inhibited the phosphorylation of p38/JNK in LPS-stimulated RAW264.7 cells. Additionally, molecular docking analysis indicated that IT24 may directly bind to the mPGES-1 protein. CONCLUSION: IT24 might inhibit mPGES-1 and the p38/JNK pathway to exert its anti-inflammatory effects and could be also developed as an inhibitor of mPGES-1 to prevent and treat mPGES-1-related diseases, such as inflammatory diseases, and holds promise for further research and drug development.

Clinical effect of Danshen decoction in patients with heart failure: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The incidence of heart failure (HF) is increasing year by year, posing a great threat to human health. Although pharmacotherapy has been able to significantly prolong patient survival, pharmacotherapy for HF still has limitations due to its complex pathogenesis and considerable individual variability, there is a great need to explore complementary and alternative therapies to slow down the progression of HF. Danshen decoction is used to treat several cardiovascular diseases including HF, but the efficacy of stabilization is uncertain. This meta-analysis evaluated the clinical efficacy of Danshen Decoction for the treatment of HF. METHODS: The registration number assigned to this meta-analysis on the PROSPERO platform is CRD42022351918. Four databases were searched, and randomized controlled trials (RCTs) of Danshen decoction combined with conventional treatment (CT) of HF were screened, CT included medical treatments other than Danshen Decoction to which the patient was treated (including but not limited to angiotensin converting enzyme inhibitor, angiotensin receptor blocker, angiotensin receptor neprilysin inhibitors, ß-blockers, diuretics, mineralcorticoid recept antagonist etc.). The clinical efficacy rate (CER), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), brain natriuretic peptide (BNP), N-terminal pro-B type natriuretic peptide (NT-proBNP) and hypersensitive C-reactive protein (hs-CRP) were included as outcome indicators. The GRADE grading scale was used to grade the above indicators. The Cochrane risk-of-bias tool and the Jadad quality scale were used to assess the methodological quality of RCTs. Finally, RevMan V.4.5 software was used for data synthesis, 95% confidence intervals (CI) for dichotomous data, risk ratios (RR), and mean differences (MD) for continuous variables were calculated, Chi-square and I2 were used for heterogeneity assessment. RESULTS: Nine RCTs with a total of 855 patients were included in this study, and all included RCTs had a low overall quality risk of bias and high quality of reported information. The results of the meta-analysis showed that compared with the use of CT, CER (%) was significantly improved due to Danshen decoction combined with CT (MD = 3.95, 95% CI [2.58, 6.04], P < 0.00001), LVEF (%) was significantly improved (MD = 5.46, 95% CI [5.32, 5.60], P < 0.00001), LVEDD (mm) was significantly reduced (MD = -5.27, 95% CI [-6.21, -4.32], P < 0.00001), LVESD (mm) was significantly reduced (MD = -4.60, 95% CI [-5.87, -3.32], P < 0.00001), BNP (pg/mL) was significantly reduced (MD = -88.61, 95% CI [-121.98, -55.24], P < 0.00001), NT-proBNP (pg/mL) was significantly decreased (SMD = -3.33, 95% CI [-5.92, -0.73], P = 0.01), hs-CRP (mg/L) was significantly decreased (MD = -2.73, 95% CI [-4.11, -1.34], P = 0.0001). The quality of the GRADE evidence for all outcomes was moderate to low and no RCTs reported adverse events. CONCLUSION: Our research demonstrates that Danshen decoction is an effective and safe treatment option for HF. Nevertheless, considering the limitations of methodological and the quality of RCTs, more rigorous, large-scale, multicenter randomized clinical trials are needed to further evaluate the efficacy and safety of Danshen decoction in the treatment of HF patients.

Chinese herbal formula ruangan granule enhances the efficacy of entecavir to reverse advanced liver fibrosis/early cirrhosis in patients with chronic HBV infection: A multicenter, randomized clinical trial.

BACKGROUND: Nucleotide analogs treatment can reverse liver fibrosis in chronic hepatitis B (CHB). However, it has limited effect on fibrosis resolution in patients with CHB, particularly in preventing progression to hepatocellular carcinoma (HCC). Ruangan granule (RG), a Chinese herbal formula, has proven to produce a therapeutic effect against liver fibrosis in animal experiment. Thus, we aimed to evaluate the effect of our Chinese herbal formula (RG) combined with entecavir (ETV) to reverse advanced liver fibrosis/early cirrhosis from CHB. METHODS: A total of 240 CHB patients with histologically confirmed advanced liver fibrosis/early cirrhosis from 12 centers were randomly and blindly allocated to consume either ETV (0.5 mg/day) plus RG (2 times/day) or control (ETV) for 48 weeks (wk) treatment. Changes in histopathology, serology and imageology were observed. Liver fibrosis reversion, defined as a reduction in the Knodell HAI score by ≥ 2 points and Ishak score by ≥ 1 grade, was assessed. RESULTS: The rate of fibrosis regression and inflammation remission after 48 wk of treatment in histopathology was significantly higher in the ETV + RG group (38.73% vs. 23.94%, P = 0.031). The ultrasonic semiquantitative scores decreased by ≥ 2 points and were 41 (28.87%) and 15 (21.13%) in the ETV+RG and ETV groups, respectively (P = 0.026). The ETV+RG group had a significantly lower Fibrosis-4 score (FIB-4) index (P = 0.028). There was a significant difference between the ETV+RG and ETV groups in the liver function normalization rate (P < 0.01). Moreover, ETV plus RG combination treatment further reduced the risk of HCC in median 55-month follow-up (P < 0.01). CONCLUSIONS: This study illustrates that the Chinese herbal formula RG with ETV can improve advanced liver fibrosis/early cirrhosis regression in patients with CHB, further reducing the risk of HCC.

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.

Material basis and integrative pharmacology of danshen decoction in the treatment of cardiovascular diseases.

BACKGROUND: Cardiovascular diseases (CVDs) are among the primary and predominant threats to human health with increasing incidence. Danshen Decoction (DSD) as an adjuvant therapy can benefit CVDs patients by improving clinical efficacy. PURPOSE: The purpose of this study was to identify the active components and potential pharmacological mechanisms of DSD by combining mass spectrometry with a network pharmacology strategy and to review the use of DSD in the treatment of CVDs. METHOD: First, the composition of DSD was analyzed by ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). Second, the network pharmacology method was used to elucidate the underlying material basis and possible pharmacological mechanism of DSD for the treatment of CVDs. Finally, clinical and experimental studies on DSD in the past ten years were retrieved from the PubMed and CNKI database, and the content of these studies was used to summarize the latest progress in DSD treatment of CVDs. OUTCOME: A total of 35 compounds were found in DSD by manual identification from the analysis of MS, which may be the material basis for the therapeutic effect of DSD. After taking the intersection of 2086 targets related to CVDs, these 35 compounds are considered to play a role in the treatment of CVDs through 210 targets including signal transducer and activator of transcription 3 (STAT3), sarcoma (SRC) and phosphoinositide-3-kinase regulatory subunit (PIK3R), and a total of 168 signaling pathways were involved in the regulation of CVDs by DSD, including PI3K-AKT signaling pathway, Alzheimer disease, and Rap1 signaling pathway. A total of 29 clinical studies using DSD in the treatment of CVDs were included in the literature review, and these studies showed the positive significance of DSD as adjuvant therapy, while 14 experimental studies included in the literature review also demonstrated the effectiveness of DSD in the treatment of CVDs. CONCLUSION: DSD plays a role in the treatment of CVDs through a variety of active ingredients. Large-scale clinical research and more in-depth experimental research will help to further reveal the mechanism of DSD in the treatment of CVDs.

Hypertensive heart disease and myocardial fibrosis: How traditional Chinese medicine can help addressing unmet therapeutical needs.

Long-term elevated blood pressure will increase the cardiac load and lead to myocardial fibrosis (MF). A variety of pathological mechanisms and signal transduction pathways are involved in the process of hypertensive MF, which is of great significance for the occurrence and development of ventricular dilatation and heart failure. MF is the pathological basis of hypertensive heart disease (HHD), and blood pressure control is the key to delaying MF and reducing the occurrence of cardiovascular events. Although a large number of experimental results suggest that anti-MF drug therapy has made great progress, the conclusions of relevant clinical trials are still not optimistic, and it is urgent to find new effective anti-MF medicine. The clinical efficacy of traditional Chinese medicine (TCM) in the treatment of MF in HHD is obvious, and some achievements have been made in the mechanism research. Studies have confirmed that a variety of TCM compound prescription and natural compounds play different degrees of inhibitory effect on MF. In this study, we reviewed the pathogenesis of MF in HHD and the current drug treatment strategies, summarized the latest research progress of TCM in the treatment of MF in HHD, and demonstrated the mechanism of its cardiac protective effect. Finally, we pointed out the limitations of the current study and prospected the future research of TCM.

The effects of Xuebijing injection combined with ulinastatin as adjunctive therapy on sepsis: An overview of systematic review and meta-analysis.

BACKGROUND: Xuebijing injection (XBJ) has increasingly been used for sepsis in China. We aimed to evaluate the methodological quality and summarize the evidence regarding the effectiveness of XBJ combined with ulinastatin (UTI) for sepsis from systematic reviews/meta-analyses (SRs/MAs). METHODS: From the inception to May 23, 2021, eight databases were searched to screen the SRs/MAs of XBJ combined with UTI in the treatment of sepsis. Methodology Quality of Systematic Reviews 2 (AMSTAR-2) was used to evaluate the quality of the methods. Grading of Recommendation,Assessment, Development, and Evaluation (GRADE) was used in the assessment of evidence quality. RESULTS: Seven SRs/MAs on XBJ combined with UTI treatment for sepsis were included. The AMSTAR-2 showed that the methodological quality of all included SRs/MAs was rated as critically low. According to the evaluation results of GRADE, 30% (13/44), 30% (13/44), and 40% (18/44) were rated to be of moderate, low, and critically low quality, respectively. Descriptive analysis results showed that XBJ combined with UTI was an effective treatment modality for sepsis. CONCLUSIONS: All included SRs/MAs showed that XBJ combined with UTI was more effective than UTI alone in the treatment of sepsis on the basis of conventional treatment, but the reliability of the results was limited due to the disadvantages of lower methodological quality and higher risk of bias in the included SRs/MAs. Further high-quality clinical studies and SRs/MAs are recommended to verify whether XBJ combined with UTI is more effective than UTI alone.

Therapeutic potential of traditional Chinese medicine against atherosclerosis: Targeting trimethylamine N-oxide.

BACKGROUND: Recent studies have shown that plasma trimethylamine-N-oxide (TMAO) level is highly correlated with the risk of atherosclerosis (AS), and the elevated level is significantly positively correlated with the incidence of AS. PURPOSE: The purpose of this article is to offer a useful summary of the correlation between TMAO and AS, and the effect of herbal monomers, herbal extracts, and formulas on anti-atherosclerosis mediated by TMAO. METHOD: The data contained in this article comes from PubMed, Web of Science, and China National Knowledge Infrastructure. RESULTS: This review discusses the main mechanism of AS induced by TMAO, including endothelial dysfunction, macrophage foaming, platelet reactivity, and cholesterol metabolism, and summarizes 6 herb monomers, 5 herb extracts, and 2 formulas that have been tested for their anti-TMAO activity. CONCLUSION: The current understanding of possible ways to reduce TMAO generation is discussed, with the effect and potential of herb monomers, herb extracts, and formulas highlighted.

Network Pharmacology Analysis and Experimental Verification Strategies Reveal the Action Mechanism of Danshen Decoction in Treating Ischemic Cardiomyopathy.

Background: Danshen Decoction comprises Salvia miltiorrhiza, Santalum album, and Amomum villosum. It can promote blood circulation and remove blood stasis, and is commonly used in the treatment of gastric and duodenal ulcers, coronary heart disease, angina pectoris, etc. This research is based on network pharmacology and is experimentally verified to explore the potential mechanism of Danshen Decoction in the treatment of ischemic cardiomyopathy (ICM). Methods: The effective components and targets of Danshen Decoction were firstly extracted from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, the drug-component-target-disease network was then constructed, the protein-protein interaction (PPI) network was constructed, the Gene Ontology (GO) enrichment analysis was carried out, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed in order to find the potential active components and therapeutic mechanisms. Finally, the in vitro hypoxia/reoxygenation model in H9c2 cells was established to verify the predicted active components and therapeutic mechanisms. Results: The results showed that Danshen Decoction has 67 potential active components and 109 therapeutic targets in treating ICM. These targets were rich in a variety of gene functions and different signaling pathways; the main gene targets include TP53, c-Jun, and Akt1. Go enrichment analysis showed that response to drug, membrane raft, and G protein-coupled amine receiver activity rank first in each process, and the main signaling pathways include PI3K-Akt signaling pathway. Through molecular docking and experimental verification of the major active components and core therapeutic targets, the active components of Danshen Decoction demonstrated an ability to reduce the cell damage caused by hypoxia/reoxygenation in H9c2 cells by regulating the core therapeutic target including Akt1, c-Jun, and TP53. Conclusion: Danshen Decoction has the effect of treating ICM in multiple ways, which is consistent with the results of network pharmacology. This laid a foundation for further study in exploring the active principles and pharmacological mechanism of Danshen Decoction.

The Role and Mechanisms of Action of Natural Compounds in the Prevention and Treatment of Cancer and Cancer Metastasis.

Cancer has emerged as one of the world's most concerning health problems. The progression and metastasis mechanisms of cancer are complex, including metabolic disorders, oxidative stress, inflammation, apoptosis, and intestinal microflora disorders. These pose significant challenges to our efforts to prevent and treat cancer and its metastasis. Natural drugs have a long history of use in the prevention and treatment of cancer. Many effective anti-tumor drugs, such as Paclitaxel, Vincristine, and Camptothecin, have been widely prescribed for the prevention and treatment of cancer. In recent years, a trend in the field of antitumor drug development has been to screen the active antitumor ingredients from natural drugs and conduct in-depth studies on the mechanisms of their antitumor activity. In this review, high-frequency keywords included in the literature of several common Chinese and English databases were analyzed. The results showed that five Chinese herbal medicines (Radix Salviae, Panax Ginseng C. A. Mey, Hedysarum Multijugum Maxim, Ganoderma, and Curcumaelongae Rhizoma) and three natural compounds (quercetin, luteolin, and kaempferol) were most commonly used for the prevention and treatment of cancer and cancer metastasis. The main mechanisms of action of these active compounds in tumor-related research were summarized. Finally, we found that four natural compounds (dihydrotanshinone, sclareol, isoimperatorin, and girinimbin) have recently attracted the most attention in the field of anti-cancer research. Our findings provide some inspiration for future research on natural compounds against tumors and new insights into the role and mechanisms of natural compounds in the prevention and treatment of cancer and cancer metastasis.

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.

Efficacy and safety of Shengmai injection as an adjunctive therapy on sepsis: A protocol for systematic review and meta-analysis.

INTRODUCTION: Sepsis is a common life-threatening, acute and severe disease with high morbidity and mortality, which seriously endangers patient health. Shengmai injection (SMI) is typically used as an alternative treatment for sepsis patients. This investigation aimed at designing a comprehensive recollection and meta-analytical exercise for evaluating efficacy and safety-profile for employing SMI against sepsis. METHODS: Multiple research literature repositories, both localized and global, were examined for randomized controlled trials of sepsis treated by SMI - from repository inception to December 2021 as a timeframe. Primary outcome measures contained 28-day all-cause mortality, while secondary outcome measures consisted of Sequential Organ Failure Assessment scorings, acute Physiology and Chronic Health Evaluation II scorings, ICU-based hospitalization length, mechanical ventilation timespan, ICU mortality rate, and adverse effects/events. RevMan V.5.3 was employed for data analyses. Two reviewers evaluated bias risks/investigation quality through Cochrane Collaboration risk of bias tool / Grades of Recommendations Assessment Development and Evaluation, separately. RESULTS: Such a comprehensive reviewing protocol review protocol systematically and objectively analyzes the effectiveness and safety-profile of SMI for therapy against sepsis, together with providing scientific grounds for clinic-based employment for SMI. PROSPERO REGISTRATION NUMBER: CRD42021245247.

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.

Traditional Chinese medicine in the treatment of nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease in clinical practice. It has been considered that NASH is one of the main causes of chronic liver disease, cirrhosis and carcinoma. The mechanism of the NASH progression is complex, including lipid metabolism dysfunction, insulin resistance, oxidative stress, inflammation, apoptosis, fibrosis and gut microbiota dysbiosis. Except for lifestyle modification and bariatric surgery, there has been no pharmacological therapy that is being officially approved in NASH treatment. Traditional Chinese medicine (TCM), as a conventional and effective therapeutic strategy, has been proved to be beneficial in treating NASH in numbers of studies. In the light of this, TCM may provide a potential therapy for treating NASH. In this review, we summarized the associated mechanisms of action TCM treating NASH in preclinical studies and systematically analysis the effectiveness of TCM treating NASH in current clinical trials.

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.