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Oleanolic acid ameliorates intestinal alterations associated with EAE.

Beatriz Gutierrez1, Isabel Gallardo1, Lorena Ruiz2,3

  • 1Instituto de Biología y Genética Molecular (IBGM-CSIC/UVa), Valladolid, Spain.

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Oleanolic acid (OA) treatment improved gut dysfunction in experimental autoimmune encephalomyelitis (EAE) mice, a model for multiple sclerosis (MS). OA normalized intestinal barrier markers and reduced inflammation, suggesting its potential for MS treatment.

Keywords:
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Area of Science:

  • Neuroimmunology
  • Gastroenterology
  • Pharmacology

Background:

  • Multiple sclerosis (MS) is a CNS autoimmune disease.
  • Intestinal dysfunction is increasingly recognized in MS pathogenesis.
  • Oleanolic acid (OA), an anti-inflammatory triterpene, shows promise in preclinical MS models.

Purpose of the Study:

  • To investigate gut intestinal dysfunction in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.
  • To evaluate the therapeutic effect of oleanolic acid (OA) on EAE-associated gut dysfunction.

Main Methods:

  • Mice with MOG35-55-induced EAE were treated with OA or vehicle.
  • Clinical deficits were monitored daily.
  • Molecular and histological analyses of serum and intestinal tissues assessed inflammatory and oxidative responses.
  • In vitro cell models (Caco-2, HT29-MTX-E12) were used to study OA effects.

Main Results:

  • OA treatment protected against increased intestinal permeability and preserved goblet cells in EAE mice.
  • OA reduced serum markers of intestinal barrier damage (iFABP) and monocyte activation (sCD14).
  • OA decreased pro-inflammatory mediators, prevented oxidative stress in the intestine, and normalized short-chain fatty acid profiles.
  • OA preserved levels of immunoregulatory cytokines, GDNF, and motilin.

Conclusions:

  • Oleanolic acid (OA) ameliorates gut dysfunction in EAE mice.
  • OA normalizes gut mucosal dysfunction markers and modulates the immune response in EAE.
  • OA shows potential as a therapeutic candidate for treating human multiple sclerosis (MS).