Cedrol ameliorates ulcerative colitis via myeloid differentiation factor 2-mediated inflammation suppression, with barrier restoration and microbiota modulation

doi:10.3748/wjg.v32.i2.114057

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jan 14, 2026; 32(2): 114057
Published online Jan 14, 2026. doi: 10.3748/wjg.v32.i2.114057

Cedrol ameliorates ulcerative colitis via myeloid differentiation factor 2-mediated inflammation suppression, with barrier restoration and microbiota modulation

Yi-Qing Zhao, Yu Zhang, Yan Qin, Rui-Ya Zhang, Jun-Ping Wang

Yi-Qing Zhao, Yu Zhang, Yan Qin, Rui-Ya Zhang, Jun-Ping Wang, Department of Gastroenterology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University, Taiyuan 030012, Shanxi Province, China

Co-first authors: Yi-Qing Zhao and Yu Zhang.

Author contributions: Wang JP and Zhao YQ designed and coordinated the study; Zhao YQ, Zhang Y, and Qin Y performed the experiments and acquired and analyzed the data; Zhao YQ, Zhang Y, and Zhang RY interpreted the data; Zhao YQ wrote the manuscript; Wang JP revised the manuscript; all authors read and approved the final version of the article.

Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research, No. 2021SYS13; Shanxi Province’s “Si Ge Yi Pi” Science and Technology Driven Medical Innovation Project, No. 2021MX03; and Shanxi Provincial Basic Research Program, No. 202403021222423.

Institutional review board statement: This study was approved by the Ethics Committee of the Shanxi Provincial People’s Hospital [No. (2024) 569].

Institutional animal care and use committee statement: All animal experiments were conducted according to a protocol approved by Shanxi Provincial People’s Hospital Experimental Animal Center [No. SYXK(Jin)2024-0002].

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request at wangjp8396@sxmu.edu.cn.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Jun-Ping Wang, MD, Chief Physician, Department of Gastroenterology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University, No. 29 Shuangtasi Street, Taiyuan 030012, Shanxi Province, China. wangjp8396@sxmu.edu.cn

Received: September 11, 2025
Revised: November 3, 2025
Accepted: November 18, 2025
Published online: January 14, 2026
Processing time: 124 Days and 0.7 Hours

Abstract

BACKGROUND

Ulcerative colitis (UC) is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe. Cedrol (CE) is a bioactive natural product present in many traditional Chinese medicines. It is known for its suppression of inflammation and mitigation of oxidative stress. Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.

AIM

To investigate the therapeutic potential and mechanisms of CE in UC.

METHODS

The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model. Network pharmacology was employed to predict potential targets and pathways. Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. The anti-inflammatory mechanisms were further verified using in vitro assays. Additionally, the gut microbiota composition was analyzed via 16S rRNA gene sequencing.

RESULTS

CE significantly alleviated colitis symptoms, mitigated histopathological damage, and suppressed inflammation. Moreover, CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins (zonula occludens 1, occludin, claudin-1). Mechanistically, CE stably bound to MD2, inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells. This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways, downregulating the expression of tumor necrosis factor-alpha, interleukin-1β, and interleukin-6. Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.

CONCLUSION

CE acted on MD2 to suppress proinflammatory cascades, promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.

Keywords: Cedrol; Ulcerative colitis; Toll-like receptor 4; Myeloid differentiation factor 2; Signaling pathways; Gut microbiota

Core Tip: Therapeutics to treat ulcerative colitis (UC) must be effective and safe. The natural compound cedrol (CE) possesses anti-inflammatory and antioxidant properties. However, its therapeutic efficacy and mechanisms in UC remain unclear. We demonstrated that CE ameliorated dextran sulfate sodium-induced colitis in mice through multifaceted mechanisms: Attenuating inflammation; Promoting intestinal barrier repair; And restoring gut microbial homeostasis. Mechanistically, CE exerted its anti-inflammatory effects by functionally inhibiting the toll-like receptor 4/myeloid differentiation factor 2 complex, thereby inhibiting the activation of proinflammatory signaling pathways. These findings highlighted the potential of CE as a promising therapeutic agent for UC.