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

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...

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Autores principales: Xin Chen, Joanne Lai, Ying Song, Nan Yang, Sacha Gnjatic, Virginia Gillespie, William Hahn, Ezra Chefitz, Nanci Pittman, Jacqueline Jossen, Keith Benkov, Marla Dubinsky, Xiu-Min Li, David Dunkin
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:521a66f5222847e49080b9430e771b592021-12-02T01:03:44ZButanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects2296-858X10.3389/fmed.2021.782859https://doaj.org/article/521a66f5222847e49080b9430e771b592021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.782859/fullhttps://doaj.org/toc/2296-858XBackground: 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.Xin ChenXin ChenJoanne LaiYing SongNan YangNan YangNan YangSacha GnjaticSacha GnjaticVirginia GillespieWilliam HahnEzra ChefitzNanci PittmanJacqueline JossenKeith BenkovMarla DubinskyXiu-Min LiXiu-Min LiDavid DunkinDavid DunkinFrontiers Media S.A.articleCrohn's diseaseherbal therapypre-clinical drug testingimmunomodulatorydrug developmentMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic Crohn's disease
herbal therapy
pre-clinical drug testing
immunomodulatory
drug development
Medicine (General)
R5-920
spellingShingle Crohn's disease
herbal therapy
pre-clinical drug testing
immunomodulatory
drug development
Medicine (General)
R5-920
Xin Chen
Xin Chen
Joanne Lai
Ying Song
Nan Yang
Nan Yang
Nan Yang
Sacha Gnjatic
Sacha Gnjatic
Virginia Gillespie
William Hahn
Ezra Chefitz
Nanci Pittman
Jacqueline Jossen
Keith Benkov
Marla Dubinsky
Xiu-Min Li
Xiu-Min Li
David Dunkin
David Dunkin
Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects
description 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.
format article
author Xin Chen
Xin Chen
Joanne Lai
Ying Song
Nan Yang
Nan Yang
Nan Yang
Sacha Gnjatic
Sacha Gnjatic
Virginia Gillespie
William Hahn
Ezra Chefitz
Nanci Pittman
Jacqueline Jossen
Keith Benkov
Marla Dubinsky
Xiu-Min Li
Xiu-Min Li
David Dunkin
David Dunkin
author_facet Xin Chen
Xin Chen
Joanne Lai
Ying Song
Nan Yang
Nan Yang
Nan Yang
Sacha Gnjatic
Sacha Gnjatic
Virginia Gillespie
William Hahn
Ezra Chefitz
Nanci Pittman
Jacqueline Jossen
Keith Benkov
Marla Dubinsky
Xiu-Min Li
Xiu-Min Li
David Dunkin
David Dunkin
author_sort Xin Chen
title Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects
title_short Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects
title_full Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects
title_fullStr Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects
title_full_unstemmed Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects
title_sort butanol purified food allergy herbal formula-2 has an immunomodulating effect ex-vivo in pediatric crohn's disease subjects
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/521a66f5222847e49080b9430e771b59
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