Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell e...Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.展开更多
Objective:To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis(AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction(MLCD) on skin damage and inflammation fact...Objective:To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis(AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction(MLCD) on skin damage and inflammation factors in an AD-like mouse model.Methods:Ninety-six male BALB/c mice were divided into normal,model,positive control(mometasone furoate),and traditional Chinese medicine treatment(MLCD) groups by a random number table.2,4-dinitrofluorobenzene was used to induce AD-like mice in all groups except the normal group.The treatment or intervention was administered for seven consecutive days on days 4,18,32,and 39.The mRNA relative expressions of interleukin-4(IL-4),IL-10,interferon-γ(IFN-γ),thymic stromal lymphopoietin(TSLP),and the TSLP receptor(TSLPR) were measured using quantitative real-time polymerase chain reaction,and the serum immunoglobulin E,IL-4,IL-10,and IFN-γ levels were detected using enzyme-linked immunosorbent assay.Results:Compared with the normal group,the hematoxylin-eosin staining of the skin lesions of the mice in the model group was significantly thickened on days 11,25,and 39.Compared with the model group,the epidermal thickness of the positive control group was significantly alleviated on day 39(P <.001),and that of the MLCD group was significantly improved on days 25 and 39(P <.001).Compared with the four observation time points,MLCD had the best treatment effect on day 39 of the experiment and significantly improved the skin damage performance and relieved pathological lesions.On day 39,compared with the model group,MLCD downregulated the skin mRNA relative expressions of IL-4(P=.009),TSLP(P=.030),and TSLPR(P <.001),and reduced the mouse serum levels of IL-4(P=.003).For other serum indicators,no significant difference was observed between the model and MLCD groups.Conclusion:MLCD improved AD-like mice skin damage by regulating the Th1/Th2 immune imbalance.展开更多
基金supported by the National Natural Science Foundation of China(82074036).
文摘Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.
基金This study was supported by the Beijing Natural Science Foundation(7192114).
文摘Objective:To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis(AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction(MLCD) on skin damage and inflammation factors in an AD-like mouse model.Methods:Ninety-six male BALB/c mice were divided into normal,model,positive control(mometasone furoate),and traditional Chinese medicine treatment(MLCD) groups by a random number table.2,4-dinitrofluorobenzene was used to induce AD-like mice in all groups except the normal group.The treatment or intervention was administered for seven consecutive days on days 4,18,32,and 39.The mRNA relative expressions of interleukin-4(IL-4),IL-10,interferon-γ(IFN-γ),thymic stromal lymphopoietin(TSLP),and the TSLP receptor(TSLPR) were measured using quantitative real-time polymerase chain reaction,and the serum immunoglobulin E,IL-4,IL-10,and IFN-γ levels were detected using enzyme-linked immunosorbent assay.Results:Compared with the normal group,the hematoxylin-eosin staining of the skin lesions of the mice in the model group was significantly thickened on days 11,25,and 39.Compared with the model group,the epidermal thickness of the positive control group was significantly alleviated on day 39(P <.001),and that of the MLCD group was significantly improved on days 25 and 39(P <.001).Compared with the four observation time points,MLCD had the best treatment effect on day 39 of the experiment and significantly improved the skin damage performance and relieved pathological lesions.On day 39,compared with the model group,MLCD downregulated the skin mRNA relative expressions of IL-4(P=.009),TSLP(P=.030),and TSLPR(P <.001),and reduced the mouse serum levels of IL-4(P=.003).For other serum indicators,no significant difference was observed between the model and MLCD groups.Conclusion:MLCD improved AD-like mice skin damage by regulating the Th1/Th2 immune imbalance.