Effect of Simiao Yongan Decoction on atherosclerotic carotid plaque in ApoE-/-mice via antagonizing Ox-LDL lipid metabolism pathway

Objective:To explore the intervention effects and mechanism of Simiao Yongan(SMYA)Decoction on carotid atherosclerotic plaque in ApoE knockout mice by antagonizing lipid metabolism of oxidation low density lipoprotein(Ox-LDL).Methods:ApoE-/-mice were fed high-fat feeding for 2 weeks,combined with perivascular collar placement(PCCP)and high fat feeding for 8 weeks to establish carotid AS plaque model.All the mouses were divided into 5 groups,after successful AS model preparation.The sham operation as well as model group intragastrically administered with deionized water.The rest mouses were intragastrically administered with SMYA decoction or Pioglitazone,or treated with Atorvastatin for 8 weeks.Then adopting automatic biochemical analyzer to test total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)content.The content of ox-LDL in serum,which was tested by enzyme-linked immunosorbent assay(ELISA).The pathological changes of carotid artery were observed by hematoxylin-eosin(HE)staining and the vascular parameters were measured.Immunohistochemical method and Western blot assay was used to detect the manifestations of protein include fatty acid binding protein 4(FABP4)and peroxisome proliferator-activated receptorγ(PPARγ)as well as matrix metalloproteinase 2(MMP 2).Results:Compared with the sham operation group,the serum ox-LDL content of the model group was increased,and the intima thickness(IT),intima-media thickness(IT/MT),plaque area(PA)as well as lumen area ratio of plaque vessels(PA/LA)were enlarged(P<0.05).Immunohistochemistry and Western blot results showed that the relative expression of FABP4 and MMP2 in the model group increased markedly,while the relative expression of PPARγsignificantly decreased.Compared SMYA decoction group and Atorvastatin group as well as Pioglitazone with model group,the serum ox-LDL content was decreased(P<0.05).In the mean time,the IT,PA,IT/MT and PA/LA in carotid artery were reduced(P<0.05).Immunohistochemistry and Western blot results showed that the expression of FABP4 and MMP2 was reduced,while PPARγprotein expression increased of mouses in each administration group.Conclusion:SMYA decoction is able to antagonize Ox-LDL,increase the expression of PPARγ,decrease the level of FABP4,reduce MMP2 in carotid arteries of ApoE-/-atherosclerotic mice,and increase the stability of plaque.

Study on mechanism of Simiao Yong'an Decoction in treatment of deep venous thrombosis based on network pharmacology

Objective:To explore the mechanism of Simiao Yong'an Decoction in treating deep venous thrombosis based on the method of network pharmacology.Methods:Through TCMSP database,the effective components of each traditional Chinese medicine in Simiao Yong'an Decoction were obtained and their targets were predicted.The targets of deep venous thrombosis were collected by CTD database,and the key targets were obtained by intersection of the component targets and the disease targets;Protein-Protein Interaction(PPI)network was constructed by String database.The drugs-components-targets-disease network map was constructed by using the software of Cytoscape 3.7.2.GO function and KEGG pathway enrichment of Simiao Yong'an Decoction in the treatment of deep venous thrombosis were analyzed by using the plug-in of ClueGo.Results:121 effective components and 137 potential targets of Simiao Yong'an Decoction were obtained.There were 1172 targets of deep venous thrombosis.There were 214 biological processes analyzed by GO Biological Process and 72 pathways analyzed by KEGG analysis.Conclusion:Simiao Yong'an Decoction may act on ESR1,AR,PTGS2 and other key targets,as well as AGE-RAGE signaling pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,RLX signaling pathway and other pathways to treat deep venous thrombosis.

Meta-analysis on clinical efficacy of Simiao Yong'an decoction in treatment of peripheral arterial occlusive diseases

Objective:To systematically evaluate the clinical efficacy and safety of Simiao Yong'an Decoction in the treatment of peripheral occlusive disease(PAOD).Methods:Eight randomized controlled clinical trials(RCT)of Simiao Yong'an Decoction in the treatment of PAOD were searched and screened from domestic and foreign databases(all from database construction to March 2020).The quality of the retrieved original studies was evaluated according to the evaluation criteria of Cochrane Handbook 5.1.0,and the included studies were meta-analyzed by RevMan5.3 software.Results:A total of 350 articles were retrieved,among which 14 studies met the inclusion criteria,with a total sample size of 1254 cases.The results of meta-analysis showed that:compared with conventional western Med,combined with Simiao Yong'an Decoction on the basis of western Med treatment can significantly improve the total clinical response rate of patients[RR=1.20,95%CI(1.14,1.27),P<0.00001],improve ankle brachial index(ABI)level[MD=0.79,95%CI(0.66,0.92),P<0.00001]and toe brachial index(TBI)level[RR=0.13,95%CI(0.10,0.16),P<0.00001],decreased c-reactive protein levels[MD=-8.55,95%CI(-8.99,-8.11),P<0.00001]and LDL levels[MD=-0.41,95%CI(-0.62,-0.19),P=0.0002],and increased HDL levels[MD=0.32(0.22,0.43),P<0.00001].There was no statistically significant difference in the incidence of adverse reactions[RR=0.50,95%CI(1.15,1.64),P=0.25].Conclusion:Simiao Yong'an Decoction combined with conventional western Med is more effective than conventional western Med in the treatment of PAOD.However,in view of the limitations of the quality of the analyzed literature,the positive results obtained in this study still need to be further verified by a large sample and multi-center clinical trial with a reliable research program.

Mechanism of Simiao Yongan decoction in the treatment of arteriosclerosis obliterans of lower extremity through JAK/STAT signaling pathway

Objective:To predict the effective components,potential targets and pathways of Simiao Yong’an Decoction in the treatment of lower extremity arteriosclerosis obliterans(ASO)based on the method of network pharmacology,and to explore the mechanism of Simiao Yong’an Decoction in treating ASO combined with cell experiment.Methods:TCMSP database was used to screen the active components and targets of Simiao Yong’an decoction,and Genecards and OMIM databases were used to obtain ASO related proteins;PPI network of drug disease target proteins was constructed by string platform;go function and KEGG pathway enrichment of Simiao Yong’an Decoction ASO target were analyzed by David database.The drug target pathway with high correlation with ASO was selected.The model of vascular smooth muscle cell injury(VSMCs)induced by ox LDL was used,and Simiao Yong’an decoction containing pharmaceutical Qing was given to verify the therapeutic effect of Simiao Yong’an Decoction on ox LDL induced VSMCs and its regulation on highly correlated target pathway.Results:A total of 126 active components of Simiao Yong'an Decoction were screened,40 targets of Simiao Yong’an Decoction ASO were selected,99 go biological processes and 48 related signal pathways were related to ASO;the experimental results showed that with the passage of time,Simiao Yongan decoction could significantly inhibit the proliferation of VSMCs(P<0.05);compared with the model group,the percentage of BrdU positive cells in each dose group of Simiao Yong’an decoction was significantly higher than that in the model group In addition,Simiao Yong’an decoction could significantly inhibit the proliferation of VSMCs(P<0.05);in addition,Simiao Yongan decoction could inhibit the levels of IL-6 and IL-1β(P<0.05);significantly inhibit the expression of PCNA,JAK2 and STAT3 mRNA(P<0.05);Conclusions:Simiao Yong’an decoction has the effect of"multi-component,multi-target and multi-channel"in the treatment of ASO.It can inhibit the activation of JAK/STAT signaling pathway,play an anti-inflammatory role and inhibit the proliferation of vascular smooth muscle cells.