Integration of network pharmacology with experimental verification reveals the hypoglycemic mechanism of coptisine in Jinqi Jiangtang tablets:inhibition of the FoxO1 signaling pathway and hepatic gluconeogenesis

Background:Jinqi Jiangtang tablets(JQJT)have been approved for the treatment of type 2 diabetes mellitus(T2DM)in China for many years.Exploring the effective substances and mechanisms of JQJT is important for its clinical application and further drug research and development.This study aimed to explore the chemical basis and mechanisms of JQJT in the treatment of T2DM.Methods:With network pharmacology,we screened substances in JQJT and their possible targets,then constructed the action network and enriched the biological functions and pathways associated with the active components,and identified the potential targets and mechanisms of JQJT in the treatment of T2DM.Based on the network pharmacology data,we explored the hypoglycemic mechanisms of coptisine in JQJT through western blot and quantitative real-time polymerase chain reaction.Results:Forty-three compounds with good pharmacokinetic properties were identified in JQJT,together with 146 potential biological targets.Among these potential targets,74 were associated with treatment of T2DM.A compound-target network of the 43 compounds against T2DM was constructed.Biological process and signal pathway enrichment analysis of the network highlighted the FoxO signaling pathway.Western blot and quantitative real-time polymerase chain reaction results showed that coptisine,but not epiberberine,significantly inhibited expression of key genes involved in hepatocyte gluconeogenesis by regulating the FoxO1 signaling pathway.Conclusion:Network pharmacology analysis and cell experiments showed that coptisine regulated glucose homeostasis by inhibiting the FoxO1 signaling pathway and hepatic gluconeogenesis,which may be one of the mechanisms of JQJT in the treatment of T2DM.

Chemical profiling of Jinqi Jiangtang tablets by HPLC-ESI-Q-TOF/MS

AIM： To profile the chemical constituents in Jinqi Jiangtang tablets. METHOD： Based on the chromatographic retention behavior, fragmentation patterns of chemical components, and published lit- eratures, a high-performance liquid chromatography coupled with electrospray ionization quadrnpole time-of-flight tandem mass spectrometry （HPLC-ESI-Q-TOF/MS） method was established to characterize and identify components in Jinqi Jiangtang tablets. RESULTS： A total of 52 chemical compounds, including eight iridoid glycosides, seven phenolic acids, twelve alkaloids, six fla- vonoids, and nineteen saponins, were identified in Jinqi Jiangtang tablets. CONCLUSION： The established method could serve as a powerful tool for structural characterization and quality control of this Chinese herbal preparation.

Metabolomic profiling reveals hypoglycemic effect of Jinqi Jiangtang tablet on type 2 diabetic rats

Background:Si-Miao Sun wrote about the Jinqi Jiangtang tablet(JQJT)that is derived from the traditional Chinese herbal medicine Huanglian(Coptis Chinensis Franch)pills in the Essential Recipes for Emergent Use Worth A Thousand Gold in C.E.652.The tablet is used to treat diabetes in China owing to its powerful hypoglycemic properties.However,little is known about the metabolic mechanisms underlying these properties.Methods:Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry-based metabolomics approach was performed to explore the metabolic mechanism of JQJT in the treatment of type 2 diabetes mellitus(T2DM).Results:The metabolomic pathway analysis and the Kyoto Encyclopedia of Genes and Genomes database were used to screen out 25 potential biomarkers and construct pertinent metabolic pathways.Five metabolites,such as allantoic acid and taurine,were downregulated and 20 metabolites were upregulated in the urine of T2DM rats.The biomarkers in the JQJT group exhibited a good callback trend.It is speculated that JQJT can alleviate T2DM by regulating the disorders of taurine,hypotaurine,phenylalanine,ascorbate,and aldarate metabolism,as well as pentose and glucuronate interconversions.Conclusion:This study will be meaningful in the clinical application of JQJT and will be valuable for further exploration of the metabolic mechanisms underlying its properties.

Clinical metabolic analysis combined with traceability of biosynthetic pathway:a new approach to quality marker of Chinese materia medica

Quality marker(Q-marker)of Chinese materia medica(CMM)plays an important role in quality control of CMM products.However,its research strategy and technique remain unclear.Based on the fact that quality standard of CMM should be associated with clinical efficacy,taking Jinqi Jiangtang tablet treating type 2 diabetes as an example,the Q-marker related to activity via the reverse analysis of drug metabolism in clinic and traceability of botanic biosynthetic pathways is discovered and validated.Therefore,we proposed a new research strategy of Q-marker of CMM with"Discovery of clinical active constituents as guidance,Reverse analysis of metabolic transformations as link,and Traceability of biosynthesis pathways as key",to improve quality control of CMM products.