ORIGINAL PAPER
Calming the inflammatory storm: 4-methylcatechol ameliorates DSS-induced colitis by suppressing the NLRP3 inflammasome signaling pathway
1
Department of General Surgery, The First People’s Hospital of Hangzhou Lin’an District (Hangzhou Medical College Affiliated Lin’an People’s Hospital), Hangzhou, China
2
Department of General Stomatology, The First People’s Hospital of Hangzhou Lin’an District (Hangzhou Medical College Affiliated Lin’an People’s Hospital), Hangzhou, China
Submission date: 2025-11-06
Final revision date: 2026-03-20
Acceptance date: 2026-05-24
Online publication date: 2026-09-24
Corresponding author
Mouchun Gong
Department of General Surgery, The First People’s Hospital of Hangzhou Lin’an District (Hangzhou Medical College Affiliated Lin’an People’s Hospital), Hangzhou, China
Department of General Surgery, The First People’s Hospital of Hangzhou Lin’an District (Hangzhou Medical College Affiliated Lin’an People’s Hospital), Hangzhou, China
KEYWORDS
ABSTRACT
Introduction:
The natural polyphenol metabolite 4-methylcatechol (4-MC) has demonstrated anti-inflammatory and antioxidant properties. However, its effectiveness in ulcerative colitis (UC) and the molecular mechanisms involved are still poorly understood. This study aimed to evaluate the protective effects of 4-MC in a dextran sulfate sodium (DSS)-induced murine colitis model, with a particular focus on its potential role in modulating the NLRP3 inflammasome pathway.
Material and Methods:
Colitis was induced in mice by administering 5% DSS in drinking water. Mice were divided into the Control, Model (DSS), Model + sulfasalazine (SASP), and Model + 4-MC groups. Disease severity was monitored through body weight changes, disease activity index (DAI) scoring, and colon length measurement. Histological injury was evaluated by H&E and TUNEL staining. Intestinal barrier integrity was examined via immunofluorescence staining of occludin and E-cadherin. Inflammatory markers (TNF-, IL-6), myeloperoxidase (MPO) activity, oxidative stress markers (SOD, MDA, GSH), and key proteins in the NF-B and NLRP3 pathways were measured by ELISA, biochemical kits, Western blot and immunofluorescence.
Results:
4-MC treatment significantly ameliorated the disease manifestations of DSS-induced colitis, including weight loss, increased DAI, and colon shortening. It attenuated colonic histopathological damage, reduced apoptosis, and increased the levels of the tight junction proteins occludin and E-cadherin. Furthermore, 4-MC suppressed the inflammatory response by decreasing TNF-, IL-6, and MPO levels. Mechanistically, 4-MC inhibited the activation of the NF-B pathway, alleviated oxidative stress, and suppressed the NLRP3 inflammasome pathway.
Conclusions:
4-MC may protect against DSS-induced colitis by enhancing intestinal barrier function, attenuating inflammatory and oxidative stress responses, and suppressing NLRP3 inflammasome activation.
The natural polyphenol metabolite 4-methylcatechol (4-MC) has demonstrated anti-inflammatory and antioxidant properties. However, its effectiveness in ulcerative colitis (UC) and the molecular mechanisms involved are still poorly understood. This study aimed to evaluate the protective effects of 4-MC in a dextran sulfate sodium (DSS)-induced murine colitis model, with a particular focus on its potential role in modulating the NLRP3 inflammasome pathway.
Material and Methods:
Colitis was induced in mice by administering 5% DSS in drinking water. Mice were divided into the Control, Model (DSS), Model + sulfasalazine (SASP), and Model + 4-MC groups. Disease severity was monitored through body weight changes, disease activity index (DAI) scoring, and colon length measurement. Histological injury was evaluated by H&E and TUNEL staining. Intestinal barrier integrity was examined via immunofluorescence staining of occludin and E-cadherin. Inflammatory markers (TNF-, IL-6), myeloperoxidase (MPO) activity, oxidative stress markers (SOD, MDA, GSH), and key proteins in the NF-B and NLRP3 pathways were measured by ELISA, biochemical kits, Western blot and immunofluorescence.
Results:
4-MC treatment significantly ameliorated the disease manifestations of DSS-induced colitis, including weight loss, increased DAI, and colon shortening. It attenuated colonic histopathological damage, reduced apoptosis, and increased the levels of the tight junction proteins occludin and E-cadherin. Furthermore, 4-MC suppressed the inflammatory response by decreasing TNF-, IL-6, and MPO levels. Mechanistically, 4-MC inhibited the activation of the NF-B pathway, alleviated oxidative stress, and suppressed the NLRP3 inflammasome pathway.
Conclusions:
4-MC may protect against DSS-induced colitis by enhancing intestinal barrier function, attenuating inflammatory and oxidative stress responses, and suppressing NLRP3 inflammasome activation.
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