Ginsenoside Rb1 Alleviates DSS-Induced Ulcerative Colitis by Protecting the Intestinal Barrier Through the Signal Network of VDR, PPARγ and NF-κB.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S481769

Yi Zhou, Xinyu Xiong, Zhe Cheng, Zekai Chen, Shizhen Wu, Yan Yu, Yujin Liu, Guang Chen, Lingli Li

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引用次数: 0

Abstract

Purpose: Ginseng (Panax ginseng Meyer) is an herbal medicine used in traditional Chinese medicine (TCM), has the effects of treating colitis and other diseases. Ginsenoside Rb1 (GRb1), a major component of ginseng, modulates autoimmunity and metabolism. However, the mechanism underlying GRb1 treatment of ulcerative colitis (UC) has not yet been elucidated. UC is a refractory inflammatory bowel disease (IBD) with a high recurrence rate, and researches on new drugs for UC have been in the spotlight for a long time.

Methods: Mice with DSS-induced UC were treated with GRb1 or 0.9% saline for 10 days. Colon tissue of UC mice was collected to detect the levels of intestinal inflammatory cytokines and integrity of the intestinal barrier. RNA-seq and network pharmacology were used to predict the therapeutic targets of GRb1 during UC treatment.

Results: GRb1 treatment alleviated intestinal inflammation and improved intestinal barrier dysfunction in UC mice. Specifically, GRb1 downregulated the levels of pro-inflammatory cytokines such as TNF-α and IL-6, while upregulating the level of the anti-inflammatory cytokine IL-10. Additionally, GRb1 treatment increased the levels of tight junction proteins including ZO-1, Occludin, and E-cadherin, which are crucial for maintaining intestinal barrier integrity. Further analyses using RNA-seq and network pharmacology suggested that these effects might involve the regulation of GRb1 in the signal transduction network of VDR, PPARγ, and NF-κB.

Conclusion: The study demonstrated that GRb1 effectively alleviated UC by modulating intestinal inflammation and protecting the integrity of the intestinal barrier through the signal transduction network of VDR, PPARγ, and NF-κB.

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人参皂苷 Rb1 通过 VDR、PPARγ 和 NF-κB 信号网络保护肠屏障，缓解 DSS 诱导的溃疡性结肠炎

目的：人参（Panax ginseng Meyer）是一种传统中药，具有治疗结肠炎和其他疾病的功效。人参的主要成分人参皂苷 Rb1（GRb1）可调节自身免疫和新陈代谢。然而，GRb1 治疗溃疡性结肠炎（UC）的机制尚未阐明。溃疡性结肠炎是一种复发率很高的难治性炎症性肠病（IBD），有关溃疡性结肠炎新药的研究一直是人们关注的焦点：方法：用 GRb1 或 0.9% 生理盐水治疗 DSS 诱导的 UC 小鼠 10 天。收集 UC 小鼠的结肠组织，检测肠道炎症细胞因子的水平和肠道屏障的完整性。RNA-seq和网络药理学被用来预测GRb1在UC治疗过程中的治疗靶点：结果：GRb1治疗缓解了UC小鼠的肠道炎症并改善了肠屏障功能障碍。具体而言，GRb1 下调了促炎细胞因子（如 TNF-α 和 IL-6）的水平，同时上调了抗炎细胞因子 IL-10 的水平。此外，GRb1还能提高紧密连接蛋白（包括ZO-1、Occludin和E-cadherin）的水平，这些蛋白对维持肠道屏障的完整性至关重要。利用 RNA-seq 和网络药理学进行的进一步分析表明，这些效应可能涉及 GRb1 在 VDR、PPARγ 和 NF-κB 信号转导网络中的调控：该研究表明，GRb1可通过VDR、PPARγ和NF-κB的信号转导网络调节肠道炎症并保护肠道屏障的完整性，从而有效缓解UC。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.