Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Integrated analysis of transcriptomics and network pharmacology reveals the therapeutic mechanism of cedrol in IBD.
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Diao Haiyang, Qin Tonghui, Zheng Yifei, Han Linlin, Zhao Yuqing
Аннотация
BACKGROUND: Previous studies have reported that ginger (Zingiber officinale) and its extracts (or components such as gingerols) can alleviate inflammatory bowel disease (IBD). Herein, we report the evaluation of Cedrol (CE), a bioactive compound from ginger, for its therapeutic potential in IBD-an application that, to our knowledge, has not been previously investigated.
PURPOSE: This study aims to investigate the therapeutic effects and underlying mechanisms of CE in the treatment of IBD.
METHODS: In vitro experiments were conducted using LPS-stimulated RAW264.7 macrophages, while in vivo studies employed a DSS-induced acute murine model of IBD. The intestinal protective effects of CE and its multi-target regulatory mechanisms were systematically elucidated by integrating network pharmacology prediction with transcriptomic analysis, and further validated using ELISA, Western blotting, qPCR, cellular thermal shift assay (CETSA), and immunofluorescence in both in vitro and in vivo models.
RESULT: CE significantly ameliorated DSS-induced colitis in mice, as demonstrated by a reduced disease activity index (DAI), attenuated colon shortening, and improved histopathological scores. In LPS-stimulated RAW264.7 macrophages, CE suppressed the production of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), decreased MDA levels, and enhanced antioxidant defenses, including superoxide dismutase (SOD), T-AOC, and the GSH/GSSG ratio. Integrated transcriptomic and network pharmacology analyses identified 15 overlapping targets between CE and IBD, with significant enrichment in the JAK/STAT and NF-κB signaling pathways. Molecular docking and cellular thermal shift assay (CETSA) confirmed direct binding of CE to COX-2 and HIF-1α. Furthermore, CE downregulated phosphorylation of JAK3/STAT3, reduced the expression of COX-2 and HIF-1α, and restored intestinal barrier integrity by upregulating the tight junction proteins ZO-1 and occludin, while downregulating claudin-2.
CONCLUSION: CE exerts significant protective effects against experimental colitis through a multi-target mechanism, involving suppression of the JAK3/STAT3 signaling pathway, modulation of NF-κB-mediated inflammation, and downregulation of COX-2 and HIF-1α expression. These actions collectively attenuate intestinal inflammation, reduce oxidative stress, and enhance gut barrier integrity by restoring tight junction proteins (ZO-1, occludin, claudin-2). Collectively, CE represents a promising natural agent for the management of IBD.
PURPOSE: This study aims to investigate the therapeutic effects and underlying mechanisms of CE in the treatment of IBD.
METHODS: In vitro experiments were conducted using LPS-stimulated RAW264.7 macrophages, while in vivo studies employed a DSS-induced acute murine model of IBD. The intestinal protective effects of CE and its multi-target regulatory mechanisms were systematically elucidated by integrating network pharmacology prediction with transcriptomic analysis, and further validated using ELISA, Western blotting, qPCR, cellular thermal shift assay (CETSA), and immunofluorescence in both in vitro and in vivo models.
RESULT: CE significantly ameliorated DSS-induced colitis in mice, as demonstrated by a reduced disease activity index (DAI), attenuated colon shortening, and improved histopathological scores. In LPS-stimulated RAW264.7 macrophages, CE suppressed the production of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), decreased MDA levels, and enhanced antioxidant defenses, including superoxide dismutase (SOD), T-AOC, and the GSH/GSSG ratio. Integrated transcriptomic and network pharmacology analyses identified 15 overlapping targets between CE and IBD, with significant enrichment in the JAK/STAT and NF-κB signaling pathways. Molecular docking and cellular thermal shift assay (CETSA) confirmed direct binding of CE to COX-2 and HIF-1α. Furthermore, CE downregulated phosphorylation of JAK3/STAT3, reduced the expression of COX-2 and HIF-1α, and restored intestinal barrier integrity by upregulating the tight junction proteins ZO-1 and occludin, while downregulating claudin-2.
CONCLUSION: CE exerts significant protective effects against experimental colitis through a multi-target mechanism, involving suppression of the JAK3/STAT3 signaling pathway, modulation of NF-κB-mediated inflammation, and downregulation of COX-2 and HIF-1α expression. These actions collectively attenuate intestinal inflammation, reduce oxidative stress, and enhance gut barrier integrity by restoring tight junction proteins (ZO-1, occludin, claudin-2). Collectively, CE represents a promising natural agent for the management of IBD.