Protective effects of total alkaloids from Dendrobium crepidatum against LPS-induced acute lung injury in mice and its chemical components
Abstract 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 IC 50 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. Highlights The total alkaloids of Dendrobium crepidatum (TAD) obviously attenuates experimental acute lung injury via a TLR4-mediated pathway. Six previously undescribed indolizine-type alkaloids were identified from TAD. Isomer (−)-dendrocrepidine F significantly inhibits NO release in LPS-stimulated macrophages. Graphical abstract Indolizine-type compounds are the main anti-inflammatory ingredient of the total alkaloids of Dendrobium crepidatum . [DISPLAY OMISSION]
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