GuiLingJi(GLJ),a classic traditional Chinese medicine(TCM)formula,is composed of over 20 herbs,according to the Pharmacopeia of the People's Republic of China.Owing to its various activities,GLJ has been used in c...GuiLingJi(GLJ),a classic traditional Chinese medicine(TCM)formula,is composed of over 20 herbs,according to the Pharmacopeia of the People's Republic of China.Owing to its various activities,GLJ has been used in clinical settings for more than 400 years in China.However,the ambiguous chemical material basis limits the development of studies on the quality control and pharmacological mechanisms of GLJ.Therefore,comprehensive characterization of the multiple chemical components of GLJ is of great significance for the modernization of this formula.Given the great variety of herbs in GLJ,both UHPLCMS and ^(1)H NMR techniques were employed in this study.In addition,solvent extraction with different polarities was used to eliminate signal interference and the concentration of trace components.A variety of MS analytic methods were also used,including implementation of a self-built compound database,diagnostic ion filtering,mass defect filtering,and Compound Discoverer 3.0 analysis software.Based on the above strategies,a total of 150 compounds were identified,including 5 amino acids,13 phenolic acids and glycosides,11 coumarins,72 flavones,20 triterpenoid and triterpenoid saponins,23 fatty acids,and 6 other compounds.Moreover,13 compounds were identified by ^(1)H NMR spectroscopy.The UHPLC-MS and ^(1)H NMR results supported and complemented each other.This strategy provides a rapid approach to analyzing and identifying the chemical composition of Chinese herbal prescriptions.The current study provides basis for further research on the quality control and pharmacological mechanism of GLJ.展开更多
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
基金support from the Shanxi Provincial Science and Technology Key Research and Development Plan(Grant Nos.:201603D3113006 and 201903D311012)。
文摘GuiLingJi(GLJ),a classic traditional Chinese medicine(TCM)formula,is composed of over 20 herbs,according to the Pharmacopeia of the People's Republic of China.Owing to its various activities,GLJ has been used in clinical settings for more than 400 years in China.However,the ambiguous chemical material basis limits the development of studies on the quality control and pharmacological mechanisms of GLJ.Therefore,comprehensive characterization of the multiple chemical components of GLJ is of great significance for the modernization of this formula.Given the great variety of herbs in GLJ,both UHPLCMS and ^(1)H NMR techniques were employed in this study.In addition,solvent extraction with different polarities was used to eliminate signal interference and the concentration of trace components.A variety of MS analytic methods were also used,including implementation of a self-built compound database,diagnostic ion filtering,mass defect filtering,and Compound Discoverer 3.0 analysis software.Based on the above strategies,a total of 150 compounds were identified,including 5 amino acids,13 phenolic acids and glycosides,11 coumarins,72 flavones,20 triterpenoid and triterpenoid saponins,23 fatty acids,and 6 other compounds.Moreover,13 compounds were identified by ^(1)H NMR spectroscopy.The UHPLC-MS and ^(1)H NMR results supported and complemented each other.This strategy provides a rapid approach to analyzing and identifying the chemical composition of Chinese herbal prescriptions.The current study provides basis for further research on the quality control and pharmacological mechanism of GLJ.
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
