P-204 Anti-inflammatory Effects of the Chinese Herbal Formula FAHF-2 in Experimental and Human IBD

Abstract

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. TNF-α and other pro-inflammatory cytokines play important roles in the pathogenesis of CD. FAHF-2 is derived from Wu-Mei-Wan used in China to treat colitis. We investigated its potential anti-inflammatory effects. FAHF-2 efficacy was tested in vivo in the CD45Rbhi RAG1-/- transfer colitis model. Weight loss, colonic histology and cytokine production were assessed. 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 ELISA and immunoassay. The effect of FAHF-2 on TNF-α producing cells was determined by flow cytometry. NFκB signaling was investigated in human lamina propria mononuclear cells upon FAHF-2 treatment by In-Cell Western. FAHF-2 treated mice had decreased weight loss (P < 0.05), improved histology (P < 0.05) and reduced TNF-α (P < 0.01), IL-17 (P < 0.05), IL-6 (P < 0.01), and IFN-γ (P < 0.05) production from MLNs. Treated human PBMCs produced less TNF-α (P < 0.001), IFN-γ (P < 0.05) and IL-12 (P < 0.01). FAHF-2 reduced the TNF-α producing monocytes (P < 0.05) and T-cells (P < 0.05) in PBMCs. Inflamed CD biopsies produced less TNF-α (P < 0.01), IL-1β (P < 0.05), IL-6 (P < 0.001), and IL-17 (P < 0.001). These effects are due to decreased NFκB activation. FAHF-2 was effective in halting progression of colitis in a murine model. In human samples, FAHF-2 inhibited both adaptive and innate immune pro-inflammatory cytokine responses in PBMCs and inflamed CD mucosa due in part to blockage of NFκB activation. This study shows that FAHF-2 has potential as a novel treatment for CD.