Revealing the material basis of MMP9-mediated activating blood and removing blood stasis drugs on Danshen-Ligusticum chuanxiong anti- vascular effect

Objective:Reveal the material basis and mechanism of angiogenesis effect of Danshen-chuanxiong herb-partners.Methods:The effective components of Danshen and chuanxiong were searched in the TCM System Pharmacology Database(TCMSP),and the drug targets were searched in the Swiss Target Prediction database;in the Disease-Gene Database(DisGeNET))Search for angiogenesis-promoting and inhibiting angiogenesis targets;use the protein interaction database(STRING)database and Cytoscape software to analyze the network core targets;use the DAVID database to enrich the drug-disease target intersection for GO and KEGG;RT-qPCR experiments verified the effect of luteolin on MMP9 gene expression;in vitro tube formation experiments analyzed the effect of luteolin on endothelial cell neovascularization.Results:After analysis,it is concluded that Danshen has 10 active ingredients and 50 angiogenesis targets;Chuanxiong has 2 active ingredients and 4 angiogenesis targets.The intersection of drug-taking targets yielded 9 targets,including AR,PARP1,MMP9,MMP2,MMP12,AKR1B10,ABCC1,CDK6,and STAT3.After analyzing the active ingredient-target network graph of Danshen/Chuanxiong,it was concluded that luteolin is the key chemical ingredient.After protein interaction(PPI)analysis,the results showed that MMP9 is the core target.The KEGG pathway is mainly enriched in 5 signaling pathways,the most important pathway is cancer-related pathways.There are 22 main biological processes of GO,which mainly involve collagen catabolism,protein extracellular matrix,metal endopeptidase activity,etc.The preliminary analysis of tubule formation experiment shows that luteolin inhibits angiogenesis and down-regulates the expression of MMP9 gene.Conclusion:Luteolin,the key chemical component of the Danshen-Ligusticum chuanxiong drug pair,inhibits angiogenesis by regulating the MMP9 target,and develops the reverse regulation of angiogenesis for the traditional Chinese medicine for promoting blood circulation and removing blood stasis on the basis of the known treatment of ischemic diseases.Provide a new perspective and theoretical basis for the use of Danshen and Chuanxiong medicine in clinical cancer patients.Reveal the material basis and mechanism of angiogenesis effect of Danshen-chuanxiong herb-partners.

Processing of Calamine with Modern Analytical Techniques:Processed with Huanglian Decoction(黄连汤)and Sanhuang Decoction(三黄汤)

Objective： To determine the pyrolysis characteristics of calcined and processed calamine, qualitatively and quantitatively compare the contents of related elements, morphology and functional groups of the pyrolysis products dried at different heating temperatures and explore the critical temperature and the optimal drying temperature for the process of calamine with Huanglian Decoction（HLD, 黄连汤） and San Huang Decoction（SHD, 三黄汤）. Methods： Pyrolysis products were prepared by programmable and constantly heating the calcined and processed calamine to or at different heating temperatures. Thermogravimetry（TG） was used to test their pyrolysis characteristics. Fourier transform infrared spectroscopy and scanning electron microscopeenergy dispersive spectrometer were used to determine their morphology, functional groups and element contents. Page model was used to investigate the constant drying kinetics of processed calamine. Results： The adding of HLD or SHD to calcined calamine（CC） can slow its weight loss in drying pyrolysis process. The temperature ranges where HLD and SHD can affect its weight loss were 65–150 ℃ and 74–180 ℃, respectively. The drying temperature was optimized as 90 ℃. The drying kinetic for the processed calamine fits Page model shows good linearity. Conclusions： The critical temperature and the optimal drying temperature where HLD and SHD can affect the weight loss rate in the process of calamine were explored using the theories and methods of both biophysical chemistry and processing of Chinese materia medica. This work provides a good example for the study of the process of other Chinese medicines using modern analytical techniques.