Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) is a disease with complex pathological mechanisms. We explored the potential molecular mechanisms behind the therapeutic functions of Qingzi Zhitong decoction (QZZTD) in the treatment of UC by network pharmacology and molecular docking. QZZTD is a formula of Chinese traditional medicine consisting of 10 herbs. The potential active ingredients of QZZTD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and UC-related target genes were obtained from GeneCards and OMIM databases. A total of 138 co-identified target genes were obtained by plotting the intersection target Venn diagram, and then the STRING database and Cytoscape software were used to establish protein-protein interaction networks and herb-ingredient-target networks. Four key active compounds and nine key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the biological functions of potential target genes were associated with DNA transcription, signaling receptor and ligand activity, cytokine activity, cellular autophagy, and antioxidant pathways, with related pathways involving the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, advanced glycosylation end product (AGE)-RAGE signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in QZZTD were further validated by molecular docking. This demonstrated that quercetin, luteolin, hyndarin, and beta-sitosterol had good binding to eight key proteins, and Akt1 was the target protein with the best binding activity, suggesting that Akt1 could be the essential mediator responsible for signaling transduction after QZZTD administration. The rat experiment verified that QZZTD inhibited PI3K-Akt pathway activation and reduced inflammation in UC. In conclusion, our study suggested four potential key active components, including quercetin, were identified in QZZTD, which could interact with Akt1 and modulate the activation of the PI3K-Akt pathway. The other three pathways may also be involved in the signaling transduction induced by QZZTD in the treatment of UC.

Coronary Heart Disease and Depression or Anxiety: A Bibliometric Analysis.

This study aimed to conduct a bibliometric analysis of published studies on the association between coronary heart disease (CHD) and depression or anxiety. The study also aimed to identify leading authors, institutions, and countries to determine research hotspots and obtain some hints from the speculated future frontiers. Publications about CHD and depression or anxiety between 2004 and 2020 were collected from the Web of Science Core Collection (WOSCC) database. Bibliographic information, such as authorship, country, citation frequency, and interactive visualization, was generated using VOSviewer1.6.16 and CiteSpace5.6.R5. In total, 8,073 articles were identified in the WOSCC database. The United States (2,953 publications), Duke University and Harvard University (214 publications), Psychosomatic Medicine (297 publications), and Denollet Johan. (99 publications) were the most productive country, institutions, journal, and author, respectively. The three hotspots of the research were "The relationship between depression and CHD," "depression and myocardial infarction," and "The characteristic of women suffering depression after MI." The four future research frontiers are predicted to be "treating depression in CHD patients with multimorbidity," "psychometric properties of instruments for assessing depression and anxiety in CHD patients," "depression or anxiety in post-PCI patients," and "other mental diseases in CHD patients." Bibliometric analysis of the association between CHD and depressive disorders might identify new directions for future research.

Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia.

Rapid increases in metabolic disorders, such as type 2 diabetes mellitus (T2DM) and hyperlipidemia, are becoming a substantial challenge to worldwide public health. Traditional Chinese medicine has a long history and abundant experience in the treatment of diabetes and hyperlipidemia, and Puerariae lobatae Radix (known as Gegen in Chinese) is one of the most prevalent Chinese herbs applied to treat these diseases. The underlying mechanism by which Gegen simultaneously treats diabetes and hyperlipidemia, however, has not been clearly elucidated to date. Therefore, we systematically explored the potential mechanism of Gegen in the treatment of T2DM complicated with hyperlipidemia based on network pharmacology. We screened the potential targets of Gegen, T2DM, and hyperlipidemia in several online databases. Then, the hub targets were analyzed by performing protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays, and finally, the complicated connections among compounds, targets, and pathways were visualized in Cytoscape. We found that isoflavones, including daidzein, genistein, and puerarin, as well as ß-sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways, such as the PI3K-Akt signaling pathway; the AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis; the PPAR signaling pathway; insulin resistance; the HIF-1 signaling pathway; the TNF signaling pathway; and others. These active ingredients also target multiple biological processes, including the regulation of glucose and lipid metabolism, the maintenance of metabolic homeostasis, and anti-inflammatory and antioxidant pathways. In conclusion, Gegen is a promising therapeutic phytomedicine for T2DM with hyperlipidemia that targets multiple proteins, biological processes, and pathways.

Efficacy and safety of ShenSongYangXin Capsule combined with antiarrhythmic drugs for atrial fibrillation: A protocol for systematic review and network meta-analysis.

BACKGROUND: Shen-Song-Yang-Xin Capsule (SSYX), a Chinese patent medicine, combined with antiarrhythmic drugs (AADs) in the treatment of atrial fibrillation (AF) has been widely applied in clinical practice, but the results are controversial. This study aims to conduct a network meta-analysis (NMA) based on data from the randomized controlled trials (RCTs) to evaluate the efficacy and safety of SSYX combined with ADDs in the treatment of AF. METHODS AND ANALYSIS: A comprehensive systematic literature search will be conducted in Cochrane Library, PubMed, Web of Science, EMBASE, Chinese Biomedical Literature Database (SinoMed), Chinese National Knowledge Infrastructure (CNKI), and WanFang database for RCTs about SSYX combined with ADDs. The primary outcomes will be the frequency of AF attack and P-wave dispersion, and the secondary outcomes will be the symptom improvements, left atrial diameter, and adverse events. Statistical analyses will be conducted by using WinBUGS software (version 1.4.3), Stata software (version 14.0) and RevMan software (version 5.3). RESULTS: The results of this NMA will provide a high-quality evidence for the efficacy of SSYX combined with ADDs in the treatment of AF, and a ranking of the therapeutic classes will also be presented. CONCLUSION: The protocol will provide updated evidence for the application of SSYX for AF. INTERNATIONAL PLATFORM OF REGISTERED SYSTEMATIC REVIEW AND META-ANALYSIS PROTOCOLS (INPLASY) REGISTRATION NUMBER:: The protocol of this systematic review and meta-analysis was registered on the INPLASY website (https://inplasy.com/inplasy-2020-8-0075/) and INPLASY registration number is INPLASY202080075.

Bao Yuan decoction and Tao Hong Si Wu decoction improve lung structural remodeling in a rat model of myocardial infarction: Possible involvement of suppression of inflammation and fibrosis and regulation of the TGF-ß1/Smad3 and NF-κB pathways.

Chronic heart failure (CHF) leads to pulmonary structural remodeling, which may be a key factor for poor clinical outcomes in patients with end-stage heart failure, and few effective therapeutic options are presently available. The aim of the current study was to explore the mechanism of action and pulmonary-protective effects of treatment with Bao Yuan decoction combined with Tao Hong Si Wu decoction (BYTH) on lung structural remodeling in rats with ischemic heart failure. In a model of myocardial infarction (MI) induced by ligation of the left anterior descending (LAD) artery, rats were treated with BYTH. Heart function and morphometry were measured followed by echocardiography, histological staining, and immunohistochemical analysis of lung sections. The levels of transforming growth factor-ß1 (TGF-ß1), type I collagen, phosphorylated-Smad3 (p-Smad3), tumor necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), active nuclear factor κB (NF-κB) and alpha smooth muscle actin (α-SMA) were detected using Western blotting. Lung weight increased after an infarct with no evidence of pulmonary edema and returned to normal as a result of BYTH. In addition, BYTH treatment reduced levels of type I collagen, TGF-ß1, and α-SMA expression and decreased the phosphorylation of Smad3 in the lungs of rats after MI. BYTH treatment also reduced the elevated levels of lung inflammatory mediators such as TNF-α, TLR4, and NF-κB. Results suggested that BYTH could effectively improve lung structural remodeling after MI because of its anti-inflammatory and anti-fibrotic action, which may be mediated by suppression of the TGF-ß1/Smad3 and NF-κB signaling pathways.

Transcutaneous electrical acupoint stimulation as an adjunct therapy for obsessive-compulsive disorder: A randomized controlled study.

BACKGROUND: Transcutaneous electrical acupoint stimulation (TEAS) is thought to have potential to treat obsessive-compulsive disorder (OCD). OBJECTIVE: The purpose of this study was to determine whether adding TEAS to cognitive behavioral therapy (CBT) and clomipramine would improve the efficacy of these conventional treatments in OCD. METHODS: In this randomized controlled trial, 360 OCD patients were assigned to receive TEAS combined with CBT plus clomipramine (Group A, n = 120), TEAS combined with CBT plus placebo (Group B, n = 120), and simulated (placebo) TEAS combined with CBT plus clomipramine (Group C, n = 120) for 12 weeks. The primary outcome was measured using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). RESULTS: OCD symptoms in all patients reduced over time, however Groups A and B had a significantly greater reduction in Y-BOCS total score and the subscale for obsession and compulsion between week 2 and week 12 compared to Group C. Groups A and B had similar scores on these measures. Both groups had significantly higher rates of clinical response than Group C (88.3% and 81.7% vs. 67.5%, respectively, p < 0.001); and higher rates of remission (30.0% and 22.5% vs. 9.2%, respectively, p < 0.001). Group B experienced fewer adverse events than the other two groups. CONCLUSIONS: TEAS enhances the efficacy of conventional OCD interventions and avoids the adverse effects associated with conventional pharmacological treatment. It can be considered as an effective adjunct intervention for OCD.