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

Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects.
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DOI:
10.3389/fmed.2021.782859
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发表时间:
2021
影响因子:
3.9
通讯作者:
Dunkin D
Dunkin D
中科院分区:
医学3区
文献类型:
--
作者:
Chen X;Lai J;Song Y;Yang N;Gnjatic S;Gillespie V;Hahn W;Chefitz E;Pittman N;Jossen J;Benkov K;Dubinsky M;Li XM;Dunkin D

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背景:肿瘤坏死因子-α在克罗恩病(CD)的发病机制中起重要作用。相反,GM-CSF在抗GM-CSF抗体阳性的CD患者中的抗炎作用可能是有益的,正如之前的GM-CSF试验所看到的那样,这些试验导致CD的临床改善。我们通过精制食品过敏草药配方-2(B-FAHF-2)开发了丁醇精制食品过敏草药配方-2(B-FAHF-2)。FHF-2抑制人外周血单核细胞和结肠粘膜产生肿瘤坏死因子-α,并在小鼠模型中消除结肠炎。我们试图研究B-FAHF-2及其组成的草药对肿瘤坏死因子-α和粒-巨噬细胞集落刺激因子产生的影响,作为治疗CD的潜在草药疗法。方法:采用高效液相色谱法测定B-FAHF-2的含量,并与原制剂FAHF-2进行比较。CD患儿PBMC分别与脂多糖、B-FAHF-2、单味药或单独培养液共同培养。结肠活检标本用或不加B-FAHF-2培养。采用双抗体夹心酶联免疫吸附试验检测肿瘤坏死因子-α和粒-巨噬细胞集落刺激因子。在CD45Rbhi转移模型中检测B-FAHF-2的体内效应。结果:B-FAHF-2具有与FAHF-2相似的高效液相指纹图谱,但当剂量为FAHF-2剂量的20%时,CD患儿外周血单个核细胞和结肠粘膜产生肿瘤坏死因子-α的量减少。B-FAHF-2可促进CD患儿PBMC和结肠粘膜产生GM-CSF,包括抗GM-CSF抗体的患儿。在B-FAHF-2‘S中草药成分中,只有黄柏能抑制肿瘤坏死因子-α和增加GM-CSF的产生。在小鼠模型中,B-FAHF-2治疗减轻了结肠炎。结论:与FAHF-2相比,B-FAHF-2在较低剂量下可减少儿童受试者外周血单个核细胞和结肠粘膜产生肿瘤坏死因子α。B-FAHF-2不依赖抗体也能增加PBMC产生GM-CSF。B-FAHF-2可能对CD患者有好处。
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.
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