Masticadienonic acid from Chios mastic gum mitigates colitis in mice via modulating inflammatory response, gut barrier integrity and microbiota

Hao Cui; Xia Li; Xue-Rui An; Wei Liu; Tao Yuan

doi:10.1016/j.phymed.2022.154518

Masticadienonic acid from Chios mastic gum mitigates colitis in mice via modulating inflammatory response, gut barrier integrity and microbiota

Phytomedicine. 2023 Jan:108:154518. doi: 10.1016/j.phymed.2022.154518. Epub 2022 Nov 2.

Authors

Hao Cui¹, Xia Li¹, Xue-Rui An², Wei Liu³, Tao Yuan⁴

Affiliations

¹ College of Life Science, Jiangxi Normal University, Nanchang 330022, China.
² School of Chemistry and Environmental Science, University and College Key Lab of Natural Product Chemistry and Application in Xinjiang, Yili Normal University, Yining 835000, China.
³ School of Chemistry and Environmental Science, University and College Key Lab of Natural Product Chemistry and Application in Xinjiang, Yili Normal University, Yining 835000, China. Electronic address: ucasliuwei@126.com.
⁴ College of Life Science, Jiangxi Normal University, Nanchang 330022, China. Electronic address: tyuan@jxnu.edu.cn.

PMID: 36403513
DOI: 10.1016/j.phymed.2022.154518

Abstract

Background: Chios mastic gum (CMG) is a traditional Greek medicine used to treat a variety of gastrointestinal disorders, including inflammatory bowel disease (IBD). However, the bioactive compounds of CMG and the mechanisms of action for controlling of IBD remain unknown.

Purpose: Masticadienonic acid (MDA) is one of the most abundant constituents isolated from CMG. This study aims to investigate the potential effects and underlying mechanisms of MDA in the pathogenesis of colitis.

Methods: The effects of MDA were evaluated using a dextran sulphate sodium (DSS)-induced acute colitis mouse model. The body and spleen weight and colon length and weight were measured and the clinical symptoms were analysed. Blood samples were collected to analyse the level of serum inflammatory markers. Colon tissues were processed for histopathological examination, evaluation of the epithelial barrier function, and investigation of the probable mechanisms of action. The gut microbiota composition was also studied to determine the mechanism for the beneficial effects of MDA on IBD.

Results: MDA could ameliorate the severity of IBD by increasing the body weight and colon length, reducing spleen weight, disease activity index, and histological score. MDA treatments reduce the release of serum inflammatory cytokines tumour necrosis factor-alpha (TNFα), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) via inhibiting the MAPK and NF-κB signalling pathways. MDA supplementation could also improve the intestinal barrier function by activating the NF-E2-related factor-2 (Nrf2) signalling pathway and restoring the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. In addition, MDA administration modulates the gut microbiota composition in DSS-induced colitis mice.

Conclusion: The results indicate that MDA attenuated experimental colitis by restoring intestinal barrier integrity, reducing inflammation, and modulating the gut microbiota. The present study provides novel insights into CMG-mediated remission of IBD and may facilitate the development of preventive and therapeutic strategies for IBD.

Keywords: Chios mastic gum; Inflammatory bowel disease; Masticadienonic acid.

MeSH terms

Animals
Colitis* / chemically induced
Colitis* / drug therapy
Colitis* / metabolism
Dextran Sulfate
Gastrointestinal Microbiome*
Inflammatory Bowel Diseases*
Interleukin-6 / pharmacology
Mastic Resin / therapeutic use
Mice

Substances

Dextran Sulfate
Interleukin-6
Mastic Resin
masticadienonic acid