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SIRT3 Activator Honokiol Inhibits Th17 Cell Differentiation and Alleviates Colitis.

Xiaotian Chen1,2, Mingming Zhang3, Fan Zhou4

  • 1Department of Clinical Nutrition, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, P.R. China.

Inflammatory Bowel Diseases
|June 19, 2023
PubMed
Summary
This summary is machine-generated.

Honokiol (HKL) extract from magnolia bark reduces T helper 17 cell differentiation, offering potential protection against colitis by activating SIRT3 and inhibiting the STAT3/RORγt pathway.

Keywords:
T helper 17 cellshonokiolmitochondrial deacetylase Sirt3signal transduction and activator of transcription 3ulcerative colitis

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Area of Science:

  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • T helper 17 (Th17) cells are implicated in the pathogenesis of inflammatory bowel diseases like ulcerative colitis (UC).
  • Honokiol (HKL), a natural magnolia bark extract, activates sirtuin-3 (SIRT3) and is proposed to have anti-inflammatory properties.

Purpose of the Study:

  • To investigate the inhibitory effects of Honokiol (HKL) on Th17 cell differentiation in the context of colitis.
  • To explore the underlying molecular mechanisms involving SIRT3 and the STAT3/RORγt signaling pathway.

Main Methods:

  • Analysis of serum cytokines, T cell subsets, SIRT3, and p-STAT3/RORγt in UC patients and healthy controls.
  • In vitro differentiation of T cells and polarization of Th17 cells from mouse and human samples, treated with HKL.
  • In vivo studies using dextran sulfate sodium (DSS)-induced colitis and IL-10-deficient mice treated with HKL.

Main Results:

  • UC patients exhibited higher IL-17 and Th17 proportions, with lower IL-10 and SIRT3 levels compared to controls.
  • HKL downregulated IL-17 and Th17 cell ratios in vitro, independent of STAT3 activation.
  • In vivo, HKL treatment improved colitis parameters, reduced Th17 cell populations, increased SIRT3 expression, and inhibited STAT3 phosphorylation and RORγt expression.

Conclusions:

  • Honokiol (HKL) demonstrates protective effects against colitis by modulating Th17 cell differentiation via SIRT3 activation.
  • Inhibition of the STAT3/RORγt signaling pathway is a key mechanism through which HKL exerts its anti-inflammatory effects.
  • HKL represents a potential therapeutic candidate for inflammatory bowel disease research.