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.

Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1

Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs,specifically the paired use of Huangqi and Danggui.Methods:Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs.Using the MTT assay and a transplanted tumor mice model,the anti-tumor effects of combination TCMs were investigated in vitro and in vivo.High content analysis and flow cytometry were then used to evaluate cellular immunity,followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms.Finally,the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments.Results:There is an optimal combination of Huangqi and Danggui that,administered as an aqueous extract,can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo.Based on network pharmacology analysis,PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui.Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract(quercetin,jaranol,isorhamnetin,kaempferol,calycosin,and suchilactone)that bind to PIK3R1.Jaranol is the most important component against breast cancer.The suchilactone/jaranol combination and,especially,the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract.Conclusions:The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.