Dendrobium crepidatum was one of the sources of Herba Dendrobii, a famous and precious traditional Chinese medicine. Indolizine-type alkaloids are the main characteristic ingredients of D. crepidatum, which possesses a variety of changeable skeletons. In the present study, we found that the total alkaloids of D. crepidatum (TAD) can inhibit the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated macrophages and showed protective effects against LPS-induced acute lung injury (ALI) in mice through downregulating the TLR4-mediated MyD88/MAPK signaling pathway. Further phytochemical study showed that six previously undescribed indolizine-type compounds, including a racemic mixture (dendrocrepidine A-E) were isolated from TAD. Meanwhile, dendrocrepidine F was separated into a pair of enantiomers by a chiral chromatography, and their absolute configurations were assigned by single-crystal X-ray diffraction analysis. The isomer (-)-dendrocrepidine F showed higher anti-inflammatory effects by inhibiting NO production in LPS-treated macrophages with an IC50 value of 13.3 μM. Taken together, indolizine-type alkaloids are the active components of D. crepidatum through downregulating the TLR4-mediated pathway, indicating some kind of therapy of TAD for ALI treatment.

中文翻译：

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铁皮石斛总生物碱对LPS致小鼠急性肺损伤及其化学成分的保护作用

铁皮石斛是名贵中药石斛的来源之一。茚蒿的主要特征成分是茚茚类生物碱，具有多种多变的骨架。在本研究中，我们发现 D. creppidatum (TAD) 的总生物碱可以抑制脂多糖 (LPS) 激活的巨噬细胞中一氧化氮 (NO) 的产生，并显示出对 LPS 诱导的急性肺损伤 (ALI) 的保护作用在小鼠中通过下调 TLR4 介导的 MyD88/MAPK 信号通路。进一步的植物化学研究表明，从 TAD 中分离出了六种以前未描述的茚茚型化合物，包括外消旋混合物（dendrocrepidine AE）。同时，通过手性色谱法将dendrocrepidine F分离成一对对映异构体，并通过单晶 X 射线衍射分析确定它们的绝对构型。异构体 (-)-dendrocrepidine F 通过抑制 LPS 处理的巨噬细胞中 NO 的产生，显示出更高的抗炎作用，IC50 值为 13.3 μM。综上所述，茚茚型生物碱通过下调 TLR4 介导的通路，是 D. crepidatum 的活性成分，表明某种 TAD 治疗 ALI 的方法。