Qingchang Wenzhong Decoction ameliorates intestinal inflammation and intestinal barrier dysfunction in ulcerative colitis via the GC-C signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa, accompanied with abdominal pain, and bloody diarrhea. Currently, clinical treatment options for UC are limited. Qingchang Wenzhong Decoction (QCWZD) is an effective prescription of traditional Chinese medicine for the treatment of UC. However, the mechanism of QCWZD in alleviating intestinal barrier dysfunction in UC has not been clearly explained. AIM OF THE STUDY: To determine the mechanism whereby QCWZD promotes the recovery of intestinal barrier dysfunction in UC. MATERIALS AND METHODS: A secondary analysis of colonic mucosa from UC patients acquired from a prior RCT clinical trial was performed. The effects of QCWZD on intestinal mucus and mechanical barriers in UC patients were evaluated using colon tissue paraffin-embedded sections from UC patients. The mechanism was further investigated by in vivo and in vitro experiments. UC mice were established in sterile water with 3.0% dextran sodium sulfate (DSS). Meanwhile, mice in the treatment group were dosed with QCWZD or mesalazine. In vitro, an intestinal barrier model was constructed using Caco-2 and HT29 cells in co-culture. GC-C plasmid was used to overexpress/knock down GC-C to clarify the target of QCWZD. HE, AB-PAS, ELISA, immunohistochemistry and immunofluorescence assays were used to assess the level of colonic inflammation and intestinal barrier integrity. Rt-qPCR, Western Blot were used to detect the expression of genes and proteins related to GC-C signaling pathway. Molecular docking was used to simulate the binding sites of major components of QCWZD to GC-C. RESULTS: In UC patients, QCWZD increased mucus secretion, goblet cell number, and promoted MUC2 and ZO-1 expression. QCWZD accelerated the recovery of UC mice from DSS-induced inflammation, including weight gain, reduced disease activity index (DAI) scores, colon length recovery, and histological healing. QCWZD promoted mucus secretion and increased ZO-1 expression in in vivo and in vitro experiments, thereby repairing mucus mechanical barrier damage. The effects of QCWZD are mediated through regulation of the GC-C signaling pathway, which in turn affects CFTR phosphorylation and MUC2 expression to promote mucus secretion, while inhibiting the over-activation of MLCK and repairing tight junctions to maintain the integrity of the mechanical barrier. Molecular docking results demonstrate the binding of the main components of QCWZD to GC-C. CONCLUSION: Our study demonstrated that QCWZD modulates the GC-C signaling pathway to promote remission of mucus-mechanical barrier damage in the UC. The clarification of the mechanism of QCWZD holds promise for the development of new therapies for UC.

Network Pharmacology Analysis of Hewei Jiangni Granule for Gastroesophageal Reflux Disease and Experimental Verification of Its Anti-Neurogenic Inflammation Mechanism.

Purpose: Proton pump inhibitors, as the first-line drugs for treating gastroesophageal reflux disease (GERD), are unable to completely relieve patients' symptoms and patients are prone to recurrence after prolonged drug withdrawal. Thus, it is crucial to find herbal medicines as a complementary and alternative treatment. Hewei Jiangni granule (HWJNG) is a classical Chinese medicinal formula with clinical therapeutic effects on GERD, but its pharmacological mechanism of action remains unclear. This study aimed to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. Methods: A network pharmacology approach was applied to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. The active ingredients of HWJNG, as well as therapeutic targets of GERD were acquired from specialized databases. The "herb-ingredient-gene-target" network for HWJNG in GERD treatment was built. The protein-protein interaction (PPI) network was constructed to screen the core coincident targets. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The core targets and signaling pathways associated with the anti-neurogenic inflammatory effect were partially verified via experiments in vivo at molecular level. Results: In total, 179 chemical ingredients in HWJNG and 298 intersection targets between GERD and HWJNG were selected from databases. A large proportion of core targets and top signaling pathways were involved in neurogenic inflammation. HWJNG significantly alleviated pathological injuries of esophagus and reversed dilated intracellular spaces. Additionally, HWJNG markedly inhibited the excessive release of inflammatory cytokines such as interleukin (IL)-1ß, IL-6, tumor necrosis factor receptor (TNF-a), as well as regulated stimulation sensors including transient receptor potential vanilloid type 1 (TRPV1) and its related neuroinflammatory mediators in GERD mice. Conclusion: HWJNG is a promising therapeutic strategy for GERD treatment via regulation of multiple targets and pathways, its effects in alleviating neurogenic inflammation are especially acknowledged.

Efficacy and safety of Qi and Blood Tonic Chinese Medicines in the treatment of COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease in 2019 (COVID-19) is a sudden public event affecting all human beings, with the rapid transmission, extensive groups affected, many complications, and high mortality. Traditional Chinese Medicine has a long history of preventing and treating infectious diseases, and numerous studies have shown that Traditional Chinese Medicine, especially herbal medicine, has a positive effect on the prevention, treatment, and post-healing recovery of this COVID-19, and herbal medicines to supplement qi and blood often occupy a certain proportion of it. However, there is no relevant meta-analysis to date. Therefore, this study aims to evaluate the efficacy and safety of qi and blood tonic herbal medicines in the treatment of COVID-19 through Systematic Review and meta-analysis to provide a reference basis for widespread clinical application. METHODS: We will search from the following databases for the period from the time of database construction to March 1st, 2023. The English databases include: PubMed, MEDLINE, EMBASE, Cochrane library, WOS, Google Scholar, and CENTRAL; The Chinese databases include: China National Knowledge Infrastructure, China Biomedical Literature Database, Technology Journal Database, and Wanfang. Randomized controlled trials in English or Chinese that include Chinese herbal medicines for tonifying Qi and Blood in the treatment of patients with COVID-19 will be included. Data were independently screened and collected by 2 investigators. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.3 software was used for the meta-analysis of the data. Primary outcome indicators included cure, mortality, and exacerbation rates (change in disease severity category, patient admission to ICU, etc.). Secondary outcome indicators included recovery rate or duration of major symptoms (e.g., fever, cough, fatigue, and weakness, etc.), rate or duration of nucleic acid conversion for severe acute respiratory syndrome coronavirus-2, improvement or recovery of chest CT performance, length of hospital stay, and other adverse events. RESULTS: This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-P guidelines to ensure clarity and completeness of reporting in all phases of the systematic review. CONCLUSION: This study will provide evidence regarding the efficacy and safety of Qi and Blood Tonic Chinese Medicines for the treatment of COVID-19. PROSPERO REGISTRATION NUMBER: CRD42022361822 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361822).

Mechanism of Datura metel on sinus bradycardia based on network pharmacology and molecular docking.

OBJECTIVE: To investigate the mechanism of action of Datura metel in the treatment of sinus bradycardia based on network pharmacology and molecular docking. METHODS: The active ingredients and targets of Datura metel were collected by TCMSP database, and the Cytoscape software was used to map to show the interrelationship. Use 5 databases: GeneCards, PharmGKB, OMIM, DisGeNET, and Drugbank to obtain targets related to sinus bradycardia; establish a protein-to-protein interaction network with the help of the STRING platform; GO and Kyoto Encyclopedia of Genes and Genomes analysis of the selected core targets using the Metascape platform; Finally, the AutoDock platform was used for molecular docking and the results were displayed through Pymol. RESULTS: 27 kinds of active ingredients of the drug were screened, including 10 kinds of main ingredients; 198 drug targets and 1059 disease targets. There are 54 targets of action in the treatment of sinus bradycardia, of which 19 targets such as AKT1, IL6, TNF, and VEGFA are the core targets of Datura metel in the treatment of sinus bradycardia. Kyoto Encyclopedia of Genes and Genomes obtained 18 results suggesting that AGE-RAGE, hepatitis C, relaxin, and JAK-STAT may be key signaling pathways. Molecular docking shows that most components of the drug have good docking ability with the core target, indicating that the prediction results have certain reliability. CONCLUSION: This study preliminarily explores the potential active ingredients and possible mechanisms of action of Datura metel in the treatment of sinus bradycardia and provides a basis for in-depth investigation of its medicinal material basis and mechanism of action.

Efficacy and safety of the Chinese herbal formula Hewei Jiangni recipe for NERD with cold-heat complex syndrome: study protocol for a double-blinded randomized controlled trial.

BACKGROUND: Proton pump inhibitor (PPI) is effective for the treatment of nonerosive gastroesophageal reflux (NERD), but long-term use of PPI is prone to have complications and recurrence after withdrawal. Traditional Chinese medicine (TCM) can relieve the symptoms of reflux and improve the quality of life. The purpose of this study is to evaluate the safety and efficacy of Hewei Jiangni recipe (HWJNR) in the treatment of NERD with cold-heat complex syndrome, and clarify the mechanism of HWJNR on NERD based on the correlation analysis of intestinal flora and metabolites. METHODS: This is a single-center, randomized controlled, double-blind, placebo-controlled clinical trial in which 72 eligible participants with NERD and TCM syndrome of intermingled heat and cold will be randomly allocated in the ratio of 1:1 to two groups: TCM group and western medicine group. The TCM group will receive HWJNR with omeprazole enteric-coated tablets placebo, while the western medicine group will receive omeprazole enteric-coated tablets with HWJNR placebo. Each group will be treated for 8 weeks. The primary outcome is the score of gastroesophageal reflux disease (GERD) health-related quality of life questionnaire (GERD-Q). Secondary outcomes include SF-36 quality of life scale (SF-36), patient-reported outcomes (PRO) self-rating scale score, syndrome score of TCM, and adverse events. Mechanistic outcome is the correlation analysis of intestinal flora and metabolites from healthy individuals and NERD participants before and after the treatment respectively. DISCUSSION: The goal of this trial is to investigate the efficacy and safety of HWJNR in the treatment of NERD with cold-heat complex syndrome, and to study the composition structure and metabolite expression profile of intestinal flora in patients with NERD through 16SrRNA sequencing and metabolomic correlation analysis of fecal flora, which makes us identify the dominant links of treatment and reveal the potential mechanism of HWJNR. ChiCTR2000041225 . Registered on 22 December 2020.

Effects of ginkgo biloba on testicle injury induced by diethylstilbestrol in mice.

To evaluate the effect of gingko biloba (EGb) on diethylstilbestrol (DES) induced testicle injury in mice. Fifty male mice were divided into a control group (A), DES group (B), and 3 EGb groups (C, D, E). The EGb-treated groups received peritoneal EGb at 8.75 (C), 17.5 (D), 35 mg/kg (E) BW daily for 7 days. The control group was given equivalent amount of normal saline. The mice in groups B, C, D and E were injected hypodermically with DES at 40 mg/kg BW daily 4 hours after the first herbal administration, while the control was given olive oil. Compared with DES group, the testis coefficients-relative testicular weight increased in the three EGb-treated groups. No significant difference was observed in epididymis coefficients. Lipid peroxidation status and antioxidant enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly elevated in testes of EGb-treated groups. Lactate dehydrogenase (LDH) activities and malonaldehyde (MDA) contents were significantly decreased in testes of the EGb groups. The results indicate that EGb protects the testis from diethylstilbestrol-induced injury.