Objective To explore the targets and mechanism of Buyang Huanwu Decoction in preventing and treating atherosclerosis through network pharmacology,molecular docking and animal experiment.Methods The main active components and related targets of Buyang Huanwu Decoction were obtained and screened through databases such as TCMSP,HERB,UniProt,PubChem,SwissADME and SwissTargetPrediction.Six disease databases such as DrugBank,GeneCards,DisGeNET,OMIM,PharmGKB and TTD were used to obtain AS related targets.R language was used to obtain common targets for the drug and disease.STRING 11.5 database was used for protein interaction network analysis,and Cytoscape 3.9.1 software was used to conduct network topology parameters and obtain core targets.GO and KEGG enrichment analysis were performed on the common targets using DAVID platform.Molecular docking of core genes with the main active components of Buyang Huanwu Decoction was conducted using AutoDock Vina 1.5.6 software.An AS mouse model was established and intervened with Buyang Huanwu Decoction.The lipid content of the mouse aortic sinus was observed using Oil Red O staining.Western blot was used to detect the expression of PI3K/AKT/p38 signaling pathway,and ELISA was used to detect the contents of TNF-α and IL-17 in mouse serum.Results A total of 104 main active components and 283 action targets of Buyang Huanwu Decoction were obtained,as well as 5 347 AS related targets and 218 common targets for drugs and disease.Buyang Huanwu Decoction may use key active components such as quercetin,kaempferol and baicalin as core targets for TP53,MAPK1,AKT1,and exert its therapeutic effect on AS through PI3K-Akt signaling pathway,TNF signaling pathway and IL-17 signaling pathway,etc.Molecular docking indicated that quercetin,luteolin,kaempferol and baicalin had good affinity with TP53,HSP90AA1,MAPK1,AKT1 and RELA targets.MAPK1 had strong binding activity with baicalin and luteolin.The experimental results showed that Buyang Huanwu Decoction could reduce the lipid content in aortic sinus of AS mice,reduce the contents of TNF-α and IL-17 in serum(P<0.01)and significantly down-regulate the expression levels of PI3K,p-AKT and p-p38 proteins(P<0.05,P<0.01).Conclusion The mechanism of Buyang Huanwu Decoction for preventing and treating AS may be related to regulating the expression of the PI3K/AKT/p38 signaling pathway,thereby reducing inflammatory response.

Objective To explore the targets and mechanism of Buyang Huanwu Decoction in preventing and treating atherosclerosis through network pharmacology,molecular docking and animal experiment.Methods The main active components and related targets of Buyang Huanwu Decoction were obtained and screened through databases such as TCMSP,HERB,UniProt,PubChem,SwissADME and SwissTargetPrediction.Six disease databases such as DrugBank,GeneCards,DisGeNET,OMIM,PharmGKB and TTD were used to obtain AS related targets.R language was used to obtain common targets for the drug and disease.STRING 11.5 database was used for protein interaction network analysis,and Cytoscape 3.9.1 software was used to conduct network topology parameters and obtain core targets.GO and KEGG enrichment analysis were performed on the common targets using DAVID platform.Molecular docking of core genes with the main active components of Buyang Huanwu Decoction was conducted using AutoDock Vina 1.5.6 software.An AS mouse model was established and intervened with Buyang Huanwu Decoction.The lipid content of the mouse aortic sinus was observed using Oil Red O staining.Western blot was used to detect the expression of PI3K/AKT/p38 signaling pathway,and ELISA was used to detect the contents of TNF-α and IL-17 in mouse serum.Results A total of 104 main active components and 283 action targets of Buyang Huanwu Decoction were obtained,as well as 5 347 AS related targets and 218 common targets for drugs and disease.Buyang Huanwu Decoction may use key active components such as quercetin,kaempferol and baicalin as core targets for TP53,MAPK1,AKT1,and exert its therapeutic effect on AS through PI3K-Akt signaling pathway,TNF signaling pathway and IL-17 signaling pathway,etc.Molecular docking indicated that quercetin,luteolin,kaempferol and baicalin had good affinity with TP53,HSP90AA1,MAPK1,AKT1 and RELA targets.MAPK1 had strong binding activity with baicalin and luteolin.The experimental results showed that Buyang Huanwu Decoction could reduce the lipid content in aortic sinus of AS mice,reduce the contents of TNF-α and IL-17 in serum(P<0.01)and significantly down-regulate the expression levels of PI3K,p-AKT and p-p38 proteins(P<0.05,P<0.01).Conclusion The mechanism of Buyang Huanwu Decoction for preventing and treating AS may be related to regulating the expression of the PI3K/AKT/p38 signaling pathway,thereby reducing inflammatory response.

Aim To explore the effect of Buyang Huanwu decoction on anti-atherosclerosis by regulating the phe-notypic transformation of vascular smooth muscle cells and serum inflammatory response based on Wnt/β-catenin signaling pathway.Methods 50 ApoE-/-mice were randomly divided into model group,Buyang Huanwu decoction modified(low,medium and high dose)groups,and atorvastatin group,with 10 mice in each group;10 C57BL/6J mice with the same genetic background were set as the control group.The mice of control group were fed with regular forages,while the mice of other five groups were fed with high-fat forages for 8 weeks for model replication.From the 9th week,they were continuously gavaged for 4 weeks.After 12 weeks,the mouse aortic roots were isolated and paraffin sections were pre-pared.Oil red O staining was used to observe the lipid content of aortic sinus.Immunohistochemical method was used to detect the expression level of bone bridge protein(OPN).Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-ot),interleukin-1β(IL-1β)and monocyte che-moattractant protein-1(MCP-1)in serum.Western blot was used to detect the protein expressions of Wnt1,β-catenin and c-myc in mice aorta.RT-PCR was used to detect the expressions of Wnt1 and β-catenin gene.Results Buyang Huanwu decoction modified(low,medium and high dose)could reduce the lipid content and OPN expression in the aortic sinus of As model mice,reduce serum levels of IL-6 and TNF-α,IL-1β and MCP-1 in mice,and downregulate the expres-sion of Wnt1 and β-catenin protein and gene.Conclusion Buyang Huanwu decoction modified exerts an anti-athero-sclerosis effect by regulating inflammatory response,and some of the mechanisms may be related to inhibiting the activation of the Wnt/β-catenin signaling pathway.

OBJECTIVE:To prepare gelatin drug carrier with biocompatible sugars as crosslinking agents and study its drug release characteristics.METHODS:Gelatin discs and microspheres cross-linked by glucose,dextran,oxidized glucose,and oxidized dextran were prepared and their swelling kinetics were determined as well.The encapsulation efficiency and drug loading rate were determined by UV spectrophotometry with aspirin and bovine serum albumin(BSA)as drug models respectively.The release rates of gelatin microspheres in simulated body were determined.RESULTS:The swelling degrees of gelatins cross-linked by glucose,oxidized glucose,dextran,and oxidized dextran were 204%,246%,166%,and 233%,respectively.The average drug-loading rate of aspirin gelatins was 8.73% as compared with 4.05% of BSA gelatin microspheres,with the average encapsulation rate of 62.55% vs.31.40%.The accumulate release rates in 2 h were 30%,14%,76%and 73% for aspirin gelatin microspheres as compared with 97.2%,86.6%,60.8% and 50.1% for BSA.CONCLUSION:All of 4 kinds of sugars can replace chemical crosslinkers for the preparation of gelatin microspheres.The natural sugar gelatin microspheres were superior to oxidized sugar in sustained release effect.