Effects and Potential Mechanism of Zhuyu Pill Against Atherosclerosis: Network Pharmacology and Experimental Validation.

Background: Atherosclerosis (AS) is an immunoinflammatory disease associated with dyslipidemia. Zhuyu Pill (ZYP) is a classic Chinese herbal compound that has been shown to exhibit anti-inflammatory and lipid-lowering effects on AS in our previous studies. However, the underlying mechanisms by which ZYP ameliorates atherosclerosis have not yet been fully investigated. In this study, network pharmacology and in vivo experiments were conducted to explore the underlying pharmacological mechanisms of ZYP on ameliorating AS. Methods: The active ingredients of ZYP were acquired from our previous study. The putative targets of ZYP relevant to AS were obtained from TCMSP, SwissTargetPrediction, STITCH, DisGeNET, and GeneCards databases. Protein-protein interactions (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted using the Cytoscape software. Furthermore, in vivo experiments were carried out for target validation in apolipoprotein E (ApoE) -/- mice. Results: Animal experiments revealed that ZYP ameliorated AS mainly through lowering blood lipids, alleviating vascular inflammation, and decreasing the levels of vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), monocyte chemotactic protein-1 (MCP-1), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Additionally, the results of Real-Time quantitative PCR revealed that ZYP inhibited the gene expressions of mitogen-activated protein kinase (MAPK) p38, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) p65. The Immunohistochemistry and Western blot assays showed the inhibitory effect of ZYP on the proteins level of p38, p-p38, p65, and p-p65. Conclusion: This study has provided valuable evidence on the pharmacological mechanisms of action of ZYP in ameliorating AS that will be useful for forming the rationale of future research studying the cardio-protection and anti-inflammation effects of ZYP.

Adjuvant Treatment with Xiaoqinglong Formula for Bronchial Asthma in Acute Attack: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: XQLF (Xiaoqinglong formula) is the most commonly used prescription of traditional Chinese medicine in the treatment of asthma. XQLF combined with western medicine has been used to treat bronchial asthma in more and more cases, and good results have been achieved. Therefore, this meta-analysis aimed to evaluate the adjuvant treatment of traditional Chinese medicine classic herbal formula XQLF with bronchial asthma in acute attack. METHODS: The following electronic databases were systematically searched from inception to April 2019: PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang, VIP Database for Chinese Technical Periodicals, and China Biology Medicine (CBM). Two reviewers searched these databases and independently evaluated all the eligible articles for inclusion. Stata 14.0 was used for data synthesis and analysis. RESULTS: A total of 33 RCTs (randomized controlled trials) including 2176 patients were enrolled. All of the patients in these studies were in the acute attack stage of asthma. We conducted subgroup analysis according to the duration of treatment, which was 14 days, 10 days, and 7 days, respectively. The overall results show that adjuvant treatment with XQLF significantly improve CER (clinical efficacy rate) (RR = 1.17; 95% CI, 1.14 to 1.21; P < 0.0001) and promote pulmonary function including FEV1 (WMD = 0.35; 95% CI, 0.27 to 0.43; P < 0.0001), PEF (SMD = 1.02; 95% CI, 0.49 to 1.55; P < 0.0001), and FVC (WMD = 0.51; 95% CI, 0.35 to 0.66; P < 0.0001). The adjuvant treatment of XQLF can also reduce serum IgE concentration (SMD = -1.39; 95% CI, 1.92 to -0.85; P < 0.0001) and serum EOS concentration at 14 days (WMD = -39.85; 95% CI, -56.20 to -23.49; P < 0.0001). CONCLUSION: This study finally showed that XQLF has the auxiliary effect of improving the efficiency, promoting the lung function, and reducing the serum IgE in the treatment of acute attack asthma. This trial is registered with CRD42019133549.

Nucleoside analogs assisted with Chinese compound prescription in treating hepatic fibrosis of chronic hepatitis B patients: A protocol of systematic review and meta-analysis.

BACKGROUND: Chronic hepatitis B is often complicated with different degrees of hepatic fibrosis, which affects the quality of life. Nucleoside analogs are recommended by almost all guidelines in the world for the treatment of chronic hepatitis B. At present, there is no specific and effective chemical and biological agents for hepatic fibrosis. In China, Chinese compound prescription combined with nucleoside analogs have been used to treat hepatic fibrosis of chronic hepatitis B patients in more and more cases, and good results have been achieved. Several Chinese compound prescriptions that have been made into proprietary Chinese medicine for the convenience of use. This article aims to systematically evaluate the efficacy and safety of Chinese medicine compounds assisting nucleoside analogs in the treatment of hepatic fibrosis in chronic hepatitis B patients. METHOD: The following databases will be searched from their inception to September 2019: PubMed, EMBASE, EBSCOhost, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), VIP Database, Wanfang Database. Languages are limited to Chinese and English. The study includes randomized controlled trials using Chinese compound prescription combined with entecavir and Chinese compound prescription combined with tenofovir disoproxil fumarate to treat hepatic fibrosis of chronic hepatitis B patients. The primary outcomes including effective rate and biochemical parameters (levels of hyaluronic acid, laminin, pre-type-III collagen and type IV collagen will be tested. Additional outcomes include liver function indexes (levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin) and levels of hepatitis B virus DNA. Stata14.0 software will be used for meta-analysis. RESULT: The efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs for hepatic fibrosis of chronic hepatitis B patients will be assessed from the effective rate, biochemical parameters, liver function indexes, and levels of hepatitis B virus DNA. CONCLUSION: The conclusion of this study will be used to evaluate the efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs in the treatment of hepatic fibrosis of chronic hepatitis B patients, as well as the adjuvant effectiveness of Chinese compound prescriptions in combined therapy. PROSPERO REGISTRATION NUMBER: CRD42020156859.

Meta-analysis of influences of Biejiajian Pill combined with entecavir on serum liver fibrosis markers of compensatory period of hepatitis b cirrhosis: Protocol of systematic review and meta-analysis.

BACKGROUND: Chronic viral hepatitis b and its related complications have caused serious harm to human health and become a worldwide public health problem. Hepatitis b cirrhosis is one of the most common complications in Asia. Traditional Chinese medicine combined with antiviral therapy has become the first choice for clinical treatment of hepatitis b Cirrhosis. Biejia Pill is an effective prescription of traditional Chinese medicine in treating Compensatory period of cirrhosis, and there are more and more clinical reports about its validity in treating Compensatory period of cirrhosis. Therefore, we designed this study protocol to evaluate the adjuvant role of Biejia Pill in the treatment of Compensatory period of cirrhosis. METHOD: Electronic Databases, PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc, (CBM), will be systematically searched from inception to July 2019. Randomized controlled trials (RCTs) on Biejiajian Pill combined with Entecavir and Entecavir alone against Compensatory period of hepatitis b cirrhosis will be included; inclusion and exclusion criteria will be used to screen the trials. liver fibrosis biomarkers including ECM or its metabolites (serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), and type IV collagen (IV-C)) will be measured as primary outcomes. Liver function, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms will be measured as secondary outcomes. RevMan5 software will be used for literature quality evaluation and data synthesis and analysis. RESULT: To evaluate the efficacy and safety of Biejiajian Pill in combination therapy by observing the outcomes of serum liver fibrosis markers, adverse reactions and liver function. CONCLUSION: This study protocol will be used to evaluate the efficacy and safety of Biejia Pill in combination with entecavir in the treatment of Compensatory period of hepatitis b cirrhosis, as well as the adjuvant treatment of Biejia Pill in combination.PROSPERO registration number: CRD42019135402.

Adjuvant treatment with Xiaoqinglong formula for bronchial asthma: Protocol of systematic review and meta-analysis.

BACKGROUND: Bronchial asthma is one of the most common chronic diseases in the world and has become a serious public health problem. Combination therapy has become the first choice for clinical treatment of bronchial asthma. In addition to the combined use of routine medication, traditional Chinese medicine as an adjuvant therapy is also considered. Xiaoqinglong Decoction (XQLD) is an effective prescription of traditional Chinese medicine in treating asthma, and there are more and more clinical reports about its combination with western medicine in treating asthma. Therefore, we designed this study protocol to evaluate the adjuvant role of XQLD in the treatment of bronchial asthma. METHOD: The following electronic databases will be systematically searched from inception to April 2019: PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Scientific Journals Database (VIP), and China Biology Medicine disc, (CBM). And the following primary outcomes will be tested, including effective rate (ER), pulmonary function (FEV1, PEF, FEV1/FVC), adverse reactions (AR). RevMan5 software will be used for literature quality evaluation and stata14.0 software will be used for data synthesis and analysis. RESULT: To evaluate the efficacy and safety of Xiaoqinglong decoction in combination therapy by observing the outcomes of efficacy, adverse reactions and pulmonary function. CONCLUSION: This study protocol will be used to evaluate the efficacy and safety of XQLD in combination with conventional drugs in the treatment of bronchial asthma, as well as the adjuvant role of XQLD in combination. PROSPERO REGISTRATION NUMBER: CRD42019133549.