Objective: To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis(AD).Methods: Sixty specific-pathog...Objective: To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis(AD).Methods: Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group,model group, whole formula group(WF), exterior-releasing formula group(ERF), interior-clearing formula group(ICF), and positive control group(PC). A mouse model of AD was established using the semiantigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and p H, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin,and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction.Results: Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly.Conclusions: Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.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
目的:通过网络药理学方法探讨连翘治疗下肢静脉性溃疡(Venous Leg Ulcers,VLU)的机制。方法:从中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)查找连翘的所有成分...目的:通过网络药理学方法探讨连翘治疗下肢静脉性溃疡(Venous Leg Ulcers,VLU)的机制。方法:从中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)查找连翘的所有成分和潜在靶点,并构建药物有效成分-靶点网络;通过Dis Ge NET、人类在线孟德尔遗传(Online Mendelian Inheritance in Man,OMIM)数据库筛选VLU的相关靶标,利用Cytoscape3.2.1软件中Bisogenet插件对连翘与VLU共同靶点进行网络拓扑分析,利用人类基因组注释数据库(DAVID)对核心靶点蛋白进行基因本体(Gene Ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Gene and Genomes,KEGG)通路富集分析。利用Auto Dock Tools 1.5.6软件对主要靶点及对应的活性成分进行分子对接验证结合强度。结果:获得到具有作用靶点的有效成分20个,药物的潜在靶点129个。2个疾病数据库收集疾病靶点242个,药物疾病共同靶点14个。网络拓扑分析获得连翘治疗VLU核心靶点155个,GO富集分析结果包括无义介导的m RNA降解、信号识别粒子(Signal Recognition Particle,SRP)依赖性共翻译蛋白靶向膜、翻译起始、病毒转录、rRNA加工、蛋白翻译、RNA聚合酶II启动子转录的负调控、通过剪接体进行m RNA剪接、病毒过程、凋亡过程的负调控等生物分析过程。KEGG富集结果显示有44条通路,主要涉及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信号通路、缺氧诱导因子1(Hypoxia Inducible Factor-1,HIF-1)信号通路等。结论:连翘治疗VLU是多成分、多靶点、多途径相互作用的结果,通过干预细胞凋亡、调控炎症反应、促进血管生成、优化胶原蛋白沉积等途径达到促进溃疡愈合的目的。展开更多
基金supported by the Natural Science Foundation of Beijing Municipality Surface Project(7192114)。
文摘Objective: To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis(AD).Methods: Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group,model group, whole formula group(WF), exterior-releasing formula group(ERF), interior-clearing formula group(ICF), and positive control group(PC). A mouse model of AD was established using the semiantigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and p H, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin,and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction.Results: Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly.Conclusions: Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.
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.
文摘目的:通过网络药理学方法探讨连翘治疗下肢静脉性溃疡(Venous Leg Ulcers,VLU)的机制。方法:从中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)查找连翘的所有成分和潜在靶点,并构建药物有效成分-靶点网络;通过Dis Ge NET、人类在线孟德尔遗传(Online Mendelian Inheritance in Man,OMIM)数据库筛选VLU的相关靶标,利用Cytoscape3.2.1软件中Bisogenet插件对连翘与VLU共同靶点进行网络拓扑分析,利用人类基因组注释数据库(DAVID)对核心靶点蛋白进行基因本体(Gene Ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Gene and Genomes,KEGG)通路富集分析。利用Auto Dock Tools 1.5.6软件对主要靶点及对应的活性成分进行分子对接验证结合强度。结果:获得到具有作用靶点的有效成分20个,药物的潜在靶点129个。2个疾病数据库收集疾病靶点242个,药物疾病共同靶点14个。网络拓扑分析获得连翘治疗VLU核心靶点155个,GO富集分析结果包括无义介导的m RNA降解、信号识别粒子(Signal Recognition Particle,SRP)依赖性共翻译蛋白靶向膜、翻译起始、病毒转录、rRNA加工、蛋白翻译、RNA聚合酶II启动子转录的负调控、通过剪接体进行m RNA剪接、病毒过程、凋亡过程的负调控等生物分析过程。KEGG富集结果显示有44条通路,主要涉及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信号通路、缺氧诱导因子1(Hypoxia Inducible Factor-1,HIF-1)信号通路等。结论:连翘治疗VLU是多成分、多靶点、多途径相互作用的结果,通过干预细胞凋亡、调控炎症反应、促进血管生成、优化胶原蛋白沉积等途径达到促进溃疡愈合的目的。
