Chen Xin, Lai Joanne, Song Ying, Yang Nan, Gnjatic Sacha, Gillespie Virginia, Hahn William, Chefitz Ezra, Pittman Nanci, Jossen Jacqueline, Benkov Keith, Dubinsky Marla, Li Xiu-Min, Dunkin David
Division of Pediatric Gastroenterology, The Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, United States.
The Mindich Child Health and Development Institute (MCHDI), The Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, United States.
Front Med (Lausanne). 2021 Nov 29;8:782859. doi: 10.3389/fmed.2021.782859. eCollection 2021.
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. 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 the CD45Rb transfer model. 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. 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.
肿瘤坏死因子-α（TNF-α）在克罗恩病（CD）的发病机制中起主要作用。相比之下，粒细胞-巨噬细胞集落刺激因子（GM-CSF）可能因其在部分患有抗GM-CSF抗体的CD患者中的抗炎作用而有益，如先前GM-CSF试验所见，该试验使CD患者临床症状得到改善。我们通过提纯食物过敏草药配方-2（FAHF-2）研发出丁醇纯化的食物过敏草药配方-2（B-FAHF-2）。FAHF-2可抑制人外周血单核细胞（PBMCs）和结肠黏膜产生TNF-α，并在小鼠模型中消除结肠炎。我们试图研究B-FAHF-2及其所含草药对TNF-α和GM-CSF产生的影响，作为治疗CD的潜在草药疗法。使用高压液相色谱法（HPLC）对B-FAHF-2进行检测，并与原始配方FAHF-2进行比较。将患有CD的儿科患者的PBMCs与脂多糖和B-FAHF-2、单一草药或仅培养基一起培养。结肠活检标本在有或无B-FAHF-2的情况下进行培养。通过酶联免疫吸附测定（ELISA）法检测TNF-α和GM-CSF。在CD45Rb转移模型中测试B-FAHF-2的疗效。B-FAHF-2具有与FAHF-2相似的HPLC指纹图谱，但在FAHF-2剂量的20%时，可降低患有CD的儿科受试者的PBMCs和结肠黏膜产生的TNF-α。B-FAHF-2可增加患有CD的儿科受试者的PBMCs和结肠黏膜产生的GM-CSF，包括那些具有抗GM-CSF抗体的受试者。在B-FAHF-2的草药成分中，只有黄柏可抑制TNF-α并增加GM-CSF的产生。在小鼠模型中，B-FAHF-2治疗可减轻结肠炎。B-FAHF-2以低于FAHF-2的剂量降低患有CD的儿科受试者的PBMCs和结肠黏膜产生的TNF-α。B-FAHF-2还可独立于抗体增加PBMCs产生的GM-CSF。B-FAHF-2可能对CD患者有益。
