Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects.

Xin Chen,Ezra Chefitz,William Hahn,Jacqueline Jossen,David Dunkin,Ying Song,Sacha Gnjatic,Joanne Lai,Xiu-Min Li,Nanci Pittman,Virginia Gillespie,Nan Yang,Keith Benkov,Marla Dubinsky

doi:10.3389/fmed.2021.782859

Abstract

Background: TNF-α has a major role in the pathogenesis of Crohn's disease (CD). In contrast, GM-CSF may be beneficial for its anti-inflammatory role in a subset of patients with CD with antibodies against GM-CSF as seen in prior trials of GM-CSF which resulted in clinical improvement in CD. We developed butanol purified Food Allergy Herbal Formula-2 (B-FAHF-2) by refining FAHF-2. FAHF-2 suppressed TNF-α production by human peripheral blood mononuclear cells (PBMCs) and colonic mucosa, and abrogated colitis in a murine model. We sought to examine the effect of B-FAHF-2 and the herbs that comprise it on TNF-α and GM-CSF production as a potential herbal therapy for the treatment of CD.Methods: B-FAHF-2 was examined using high pressure liquid chromatography (HPLC) and compared to the original formulation, FAHF-2. PBMCs from pediatric patients with CD were cultured with lipopolysaccharide and B-FAHF-2, individual herbs or medium alone. Colonic biopsy specimens were cultured with or without B-FAHF-2. TNF-α and GM-CSF were measured by enzyme-linked immunosorbent assay (ELISA). B-FAHF-2 efficacy was tested in vivo in the CD45Rbhi transfer model.Results: B-FAHF-2 had a similar HPLC fingerprint as FAHF-2 but decreased TNF-α production by PBMCs and colonic mucosa from pediatric CD subjects at 20% of the FAHF-2 dose. B-FAHF-2 increased GM-CSF production by PBMCs and colonic mucosa from pediatric CD subjects including those with antibodies to GM-CSF. Of B-FAHF-2's herbal constituents, only Huang Bai suppressed TNF-α and increased GM-CSF production. In the murine model, B-FAHF-2 treatment alleviated colitis.Conclusions: B-FAHF-2 decreased TNF-α production by PBMCs and colonic mucosa from pediatric subjects at a lower dose than FAHF-2. B-FAHF-2 also increased GM-CSF production by PBMCs independent of antibodies. B-FAHF-2 may have a benefit in CD patients.

Highlights

Crohn’s disease (CD), a form of inflammatory bowel disease (IBD), is a life-long disease characterized by chronic and relapsing inflammation of the gastrointestinal tract
We found that the purified form, B-Food Allergy Herbal Formula-2 (FAHF-2), significantly suppressed the production of TNF-α by peripheral blood mononuclear cells (PBMCs) and intestinal mucosal from pediatric subjects with CD and abrogated colitis in a murine model at a much lower dose than FAHF-2
We first tested the effect of B-FAHF-2 (60 μg/ml) on TNF-α secretion by PBMCs from 29 CD subjects and 12 non-IBD controls (Table 2)

Summary

Introduction

Crohn’s disease (CD), a form of inflammatory bowel disease (IBD), is a life-long disease characterized by chronic and relapsing inflammation of the gastrointestinal tract. CD has multiple clinical phenotypes and disease severities that determine which therapy is utilized. There are numerous treatment options for children and adults with moderate-to-severe CD, but few that are approved to treat those with mild-to-moderate disease. The only FDA approved medication for treatment of mild-to-moderate CD in children 8 years and older is Entocort EC (budesonide). The indications allow for up to 10 weeks of use in active disease but not for use as a maintenance therapy in children. Other medications including immunomodulators and biologics are used off-label for mildto-moderate CD in children and have risks for significant adverse effects. TNF-α has a major role in the pathogenesis of Crohn’s disease (CD). We sought to examine the effect of B-FAHF-2 and the herbs that comprise it on TNF-α and GM-CSF production as a potential herbal therapy for the treatment of CD

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