Ganoderic acid C1 isolated from the anti-asthma formula, ASHMI™ suppresses TNF-α production by mouse macrophages and peripheral blood mononuclear cells from asthma patients.
Ganoderic acid C1 isolated from the anti-asthma formula, ASHMI™ suppresses TNF-α production by mouse macrophages and peripheral blood mononuclear cells from asthma patients.
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DOI：
10.1016/j.intimp.2015.05.018
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发表时间：
2015-08
影响因子：
5.6
通讯作者：
Li XM
中科院分区：
文献类型：
--
作者：
Liu C;Yang N;Song Y;Wang L;Zi J;Zhang S;Dunkin D;Busse P;Weir D;Tversky J;Miller RL;Goldfarb J;Zhan J;Li XM
哮喘是一种异质性气道炎症性疾病，与Th 2细胞介导的炎症和非Th 2细胞介导的炎症有关。与Th 2介导的炎症不同，TNF-α介导的哮喘炎症通常对吸入性皮质类固醇（ICS）不敏感。ASHMITM，三种草药-灵芝（Ganoderma lucidum）（G. lucidum）、苦参（Sophora flavescens Ait（S. flavescens）和甘草（G. uralensisFischer（G. uralensis），显示出高安全性，并且在哮喘患者中具有临床益处。它还抑制小鼠哮喘模型中的Th 2和TNF-α相关炎症。我们以前确定G. uralensisflavonoids是负责ASHMITM抑制Th 2介导的炎症的关键活性化合物。到目前为止，对ASHMITM中提出的抗TNF-α化合物的研究有限。本研究的目的是分离和鉴定ASHMITM中的TNF-α抑制化合物。在这里，我们报告说，G。lucidum，而不是其他两种草药提取物，S. FlavescensorG. uralensin抑制小鼠巨噬细胞的TNF-α产生;二氯甲烷（MC）-三萜类富集组分，而不是多糖富集组分，含有抑制化合物。在从MC组分中分离的15种三萜类化合物中，只有灵芝酸C1（GAC 1）显著降低了哮喘患者的小鼠巨噬细胞（RAW 264.7细胞）和外周血单核细胞（PBMC）产生的TNF-α。抑制作用与NF-κB表达下调、MAPK和AP-1信号通路部分抑制有关。灵芝酸C1可能具有治疗TNF-α介导的哮喘和其他炎性疾病炎症的潜力。
Asthma is a heterogeneous airway inflammatory disease, which is associated with Th2 cytokine-driven inflammation and non-Th2, TNF-α mediated inflammation. Unlike Th2 mediated inflammation, TNF-α mediated asthma inflammation is generally insensitive to inhaled corticosteroids (ICS). ASHMITM, aqueous extract of three medicinal herbs—Ganoderma lucidum (G. lucidum), Sophora flavescens Ait (S. flavescens) and Glycyrrhiza uralensis Fischer (G. uralensis), showed a high safety profile and was clinically beneficial in asthma patients. It also suppresses both Th2 and TNF-α associated inflammation in murine asthma models. We previously determined thatG. uralensisflavonoids are the key active compounds responsible for ASHMITM suppression of Th2 mediated inflammation. Until now, there are limited studies on anti-TNF-α compounds presented in ASHMITM. The objective of this study was to isolate and identify TNF-α inhibitory compounds in ASHMITM. Here we report thatG. lucidum, but not the other two herbal extracts,S. flavescensorG. uralensisinhibited TNF-α production by murine macrophages; and that the methylene chloride (MC)–triterpenoid-enriched fraction, but not the polysaccharide-enriched fraction, contained the inhibitory compounds. Of the 15 triterpenoids isolated from the MC fraction, only ganoderic acid C1 (GAC1) significantly reduced TNF-α production by murine macrophages (RAW 264.7 cells) and peripheral blood mononuclear cells (PBMCs) from asthma patients. Inhibition was associated with down-regulation of NF-κB expression, and partial suppression of MAPK and AP-1 signaling pathways. Ganoderic acid C1 may have potential for treating TNF-α mediated inflammation in asthma and other inflammatory diseases.