Background: Crohn's disease (CD) is a chronic inflammatory disease with increasing incidence in children. Current medications have potentially serious side effects, hence increasing interest in alternative therapies. We previously developed an herbal formula, FAHF-2, based on a classical traditional Chinese herbal formula Wu Mei Wan that has long been used in China to treat colitis. We investigated FAHF-2's potential anti-inflammatory effects.
Methods: FAHF-2 efficacy was tested in vivo in the CD45RbhiRAG1−/− transfer colitis model. Weight loss, colonic histology, and cytokine production from mesenteric lymph nodes were assessed. Human peripheral blood mononuclear cells (PBMCs) and colonic biopsies were obtained from children newly diagnosed with CD and controls and cultured with or without FAHF-2. Cytokine levels were measured by multiplex immunoassay. The effect of FAHF-2 on TNF-α–producing cells was determined by flow cytometry. NF-κB signaling was investigated in human lamina propria mononuclear cells upon FAHF-2 treatment by In-Cell Western.
Results: FAHF-2–treated mice had decreased weight loss, improved histology, and reduced TNF-α, IL-17, IL-6, and IFN-γ production. In vitro treated PBMCs produced less TNF-α, IFN-γ, and IL-12. FAHF-2 reduced the TNF-α–producing monocytes and T cells. Inflamed CD biopsies produced less TNF-α, IL-17, IL-6, and IL-1β. These effects are because of decreased NF-κB activation.
Conclusions: FAHF-2 inhibited both adaptive and innate immune proinflammatory cytokine responses in PBMCs and inflamed CD mucosa due in part to blockage of NF-κB activation. FAHF-2 was effective in halting progression of colitis in a murine model. This study shows that FAHF-2 has potential as a novel treatment of CD.
Article first published online 21 November 2013
*Division of Allergy and Immunology, Department of Pediatrics, Jaffe Food Allergy Institute;
†Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics; and
‡Division of Clinical Immunology, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York; and
§Department of Pathology, Columbia University Medical School, New York, New York.
Reprints: Xiu-Min Li, MD, MS, Division of Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029-6574 (e-mail: firstname.lastname@example.org).
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Supported by Crohn's and Colitis Foundation of America Career Development Award and Molly's Research Fund (D.D) and the National Institutes of Health/National Center for Complementary and Alternative Medicine grants 1R01AT001495-01A1 and 2R01AT001495-05A1 (X.-M.L.).
Y. Song, and D. Dunkin contributed equally to this study.
X.-M. Li is a consultant for the FAI and has shares of US Patent PCT/US 05/08600 on FAHF-2 and Herbal Springs, LLC. The other authors have no conflicts of interest to disclose.
Received July 27, 2013
Accepted September 26, 2013