Protective effects of guggulsterone against colitis are associated with the suppression of trem-1 and modulation of macrophages

Xiumei Che, Ki Cheong Park, Soo Jung Park, You Hyun Kang, Hyun A. Jin, Joo Wan Kim, Dong Hyuk Seo, Dae Kyu Kim, Tae Il Kim, Won Ho Kim, Seung Won Kim, Jae Hee Cheon

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Triggering receptor expressed on myeloid cells 1 (TREM-1)-expressing intestinal macrophages are significantly increased in the colons of patients with inflammatory bowel disease (IBD). We focused here on the effects of guggulsterone on macrophage modulation in colitis as a potential therapeutic molecule in human IBD and explore the underlying mechanisms. Gene expression in macrophages was examined and wound-healing assay using HT-29 cells was performed. Colitis in wild-type and IL-10-, Toll-like receptor 4 (TLR4)-, and myeloid differentiation primary response 88 (MyD88)-deficient mice was induced via the administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the colon. In both in vitro and in vivo experiments, guggulsterone suppressed intestinal inflammation amplified by TREM-1 stimulation, in which the suppression of NF-_B, activating protein-1, and proteasome pathways was involved. In the TNBS-induced colitis model, guggulsterone reduced disease activity index scores and TREM-1 expression, stimulated IL-10 production, and improved survival in wild-type mice. These effects were not observed in IL-10-, TLR4-, and MyD88-deficient mice. Guggulsterone also suppressed M1 polarization, yet induced the M2 phenotype in macrophages from IBD patients as well as from mice. These findings indicate that guggulsterone blocks the hyperactivation of macrophages via TREM-1 suppression and induces M2 polarization via IL-10 mediated by the TLR4 signaling pathway. Furthermore, this study provides a new rationale for the therapeutic potential of guggulsterone in the treatment of IBD. NEW & NOTEWORTHY We found that guggulsterone attenuates triggering receptor expressed on myeloid cells 1 (TREM-1)-mediated hyperactivation of macrophages and polarizes macrophages toward the M2 phenotype. This was mediated by IL-10 and partly Toll-like receptor 4 signaling pathways. Overall, these data support that guggulsterone as a natural plant sterol modulates macrophage phenotypes in colitis, which may be of novel therapeutic importance in inflammatory bowel disease treatment.

Original languageEnglish
Pages (from-to)G128-G139
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number1
Publication statusPublished - 2018 Jul

Bibliographical note

Publisher Copyright:
© 2018 American Physiological Society. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


Dive into the research topics of 'Protective effects of guggulsterone against colitis are associated with the suppression of trem-1 and modulation of macrophages'. Together they form a unique fingerprint.

Cite this