Catechol-O-Methyltransferase Loss Drives Cell-Specific Nociceptive Signaling via the Enteric Catechol-O-Methyltransferase/microRNA-155/Tumor Necrosis Factor α Axis

Zhou, QiQi; Yang, Liuqing; Verne, Meghan L; Zhang, Benjamin B; Fields, Jeremy Z.; Verne, G. Nicholas

doi:10.1053/j.gastro.2022.12.041

Cited by 2 publications

(1 citation statement)

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“…Essential oil from Liquidambar formosana leaves has certain anti-in ammatory activity, which can ameliorates in ammatory response in lipopolysaccharideactivated mouse macrophages [31] .The remarkable clinical e cacy of CYN tablets may come from the comprehensive effect of multi-components and multi-targets of different herbs. Identi cation and analysis using liquid chromatography-tandem mass spectrometry (LC-MS) revealed that the main active components of CYN (a TCM formula) include quercetin, gallic acid, catechol, luteolin, kaempferol, etc., which possess various biological activities such as anti-in ammatory, visceral pain relief, antioxidant, alleviation of visceral hypersensitivity, and modulation of gut microbiota [32][33][34][35][36] .…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of Changyanning tablets in the treatment of diarrhea-predominant irritable bowel syndrome and its effect on gut microbiota：Study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

Ban,

Zhang,

Yan

et al. 2024

Preprint

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Background Irritable Bowel Syndrome (IBS) is a chronic gastrointestinal disorder characterized by functional abnormalities in the digestive system. It is a complex condition with multifaceted pathophysiological mechanisms, which are thought to involve disruptions in the balance of gut microbiota. Diarrhea-predominant irritable bowel syndrome (IBS-D) is the most common subtype, characterized by high prevalence, recurrent symptoms, and significant impact on patients' quality of life. Current conventional treatments mainly focus on symptomatic relief but have limited efficacy. Changyanning (CYN) tablets, a traditional Chinese medicine formulation developed based on classical clinical experience, have been widely used in clinical practice. However, it remains unclear whether their therapeutic effects are mediated through modulation of the gut microbiota. This study aims to confirm the efficacy and safety of CYN tablets in IBS-D and explore their microbiological mechanisms of action. Methods This study is a multicenter, double-blind, placebo-controlled, randomized clinical trial. A total of 240 IBS-D patients were recruited and randomly assigned in a 1:1 ratio to either the CYN tablets group or the placebo group. All participants underwent a 2-week screening period before enrollment, followed by an 8-week treatment period and a 4-week follow-up period. Fecal samples were collected from the participants at weeks 0, 4, 8, and 12 for high-throughput 16S rRNA sequencing and untargeted metabolomics analysis. The primary outcome was the weekly response rate of IBS-D patients at week 8. Secondary outcomes included the weekly response rate, diarrhea response rate, abdominal pain response rate, Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS), Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), and assessment of stool frequency at weeks 2, 4, 6, and 12. Safety outcomes, such as adverse events, were also assessed. Mechanistic research outcomes focused on changes in the gut microbiota and metabolites before and after intervention in IBS-D patients. Discussion The purpose of the study is to further clarify the efficacy and safety of CYN tablets in the treatment of IBS-D through high-quality evidence-based evidence, so as to provide more reliable and safer therapeutic drugs for the clinical treatment of IBS-D. In addition, through the combined application of high-throughput 16S rRNA sequencing technology and non-targeted metabolomics technology, the purpose is to explore the key flora and metabolites of the regulation of IBS-D by CYN tablets, and provide an in-depth and comprehensive perspective on the molecular mechanism of intestinal microbial regulation of IBS-D by CYN tablets. Trial registration The trial protocol (CYNP-IBS-2022, version1.2, June 1, 2023) was registered on January 13, 2023, in the ClinicalTrials. gov database with the identifier NCT05687435. https://clinicaltrials.gov/.

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