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Objective:To explore the molecular targets and therapeutic mechanism of Er Miao San in the treatment of atopic dermatitis (AD), analyzing its active ingredients, moleculartargets and network analysis. Methods:The active ingredients and targets of Er Miao San were obtained from Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Drugbank databases. The differential expression genes of AD were obtained by Intergovernmental Group on Earth Observations (GEO) database. The target genes of Er Miao San in the treatment of AD were obtained by using Cytoscape plugin Bisogenet and CytoNCA. Enrichment analysis was obtained from the DAVID database. Results:In total, 12 active ingredients and 107 targets of Er Miao San were screened out by TCMSP and Drugbank databases; 274 differential expression genes (with an adjust P value < 0.005 and |log2 (fold change)|>1.5) were identified between AD patient and control groups using the intergovernmental Group on Earth Observations (GEO) database. 187 target genes of Er Miao San against AD were finally identified by using Cytoscape plugin Bisogenet and CytoNCA. The functional annotations of target genes were related to telomere organization, protein heterotetramerization, regulation of gene expression and so on. Twenty pathways including PI3K-Akt, MAPK and HIF-1 signaling pathway were significantly enriched. Several genes including MAPK1, AKT, RELA and TP53 were the key genes in the gene-pathway network of Er Miao San treating AD. Conclusion:This study suggested that quercetin, tetrahydroberberine, stigmastol and other core ingredientss in Er Miao San may treat AD by participating in PI3K-Akt, MAPK, HIF-1 and other signaling pathways, and regulating the core gene targets of MAPK1, Akt, Rela and TP53.
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Objective To study the anti-rheumatoid arthritis mechanism of Ermiao powder by high-throughput urine metabolomics.Methods The rats were randomly divided into control group,model group and administration group with 8 rats in each group.The rat model of rheumatoid arthritis was established by intradermal injection of complete Freund's adjuvant.Rats in control group were given Ermiao power solution 0.108 g/ml by gavage.The degree of joint swelling in rats was observed and scored.On this basis,metabolic data of rat urine samples were collected for metabolomic analysis.Unsupervised and supervised pattern recognition technology was used to analyze the high-throughput biological information data and reduce the dimension.Metabolic information related to rheumatoid arthritis was screened and focused to clarify the pathogenesis of rheumatoid arthritis and the therapeutic mechanism of Ermiao power.Results Compared with the model group,the swelling degree of the foot (1.93 ± 0.11 vs.2.36 ± 0.19) in Ermiao power group significantly decreased (P＜0.01).Metabolic profiles showed that the metabolic distribution of healthy rats was significantly separated from that of model rats,and the treatment group was in the middle of the two groups.From the macro-metabolic point of view,the metabolism of model rats changed dramatically.The Ermiao power had a good intervention effect on rheumatoid arthritis.Thirteen biomarkers related to rheumatoid arthritis were identified by database matching,including linolenic acid,arachidonic acid,5,6-EET,alpha-lactose,sucrose,trehalose,prostaglandins and leukotriene C4.It involved linoleic acid metabolism,arachidonic acid metabolism,starch and galactose metabolism and sphingolipid metabolism.Conclusions The Ermiao power has significant therapeutic effect on rheumatoid arthritis rats.Regulation of the linoleic acid metabolism,arachidonic acid metabolism,starch and galactose metabolism may be the mechanism of its treatment of rheumatoid arthritis.
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BACKGROUND: Various health benefits have been attributed to Er-Miao-San (EMS), a traditional Chinese herbal formulation that contains equal amounts of cortex phellodendri (Phellodendron amurense Ruprecht) and rhizoma atractylodis (Atractylodes lancea D.C). However, its effect on the anti-inflammatory activity in human dermal fibroblasts (HDFs) and the mechanism underlying this effect are unknown. RESULTS: This study investigated the effects of EMS on TNF-α-induced MMP-1 expression in HDFs. Our data show that EMS inhibited TNF-α-induced MMP-1 expression in a concentration-dependent manner. Interestingly, EMS maintained IkB content without inhibiting the phosphorylation of MAPKs, which are well-established upstream kinases of NF-kB. Moreover, EMS reduced the level of nuclear p65 protein in HDFs. Luciferase assay revealed that EMS inhibits the transcriptional activity of NF-kBbystabilizing IkB. Our results show that EMS exerts its anti-inflammatory effect by inhibiting NF-kB-regulated genes such as IL-1ß and IL-8. Moreover, EMS effectively inhibited TNF-α-induced expression of MMP-1 via the NF-kBpathway. CONCLUSIONS: Taken together, our data suggest that EMS could potentially be used as an anti-inflammatory and anti-aging treatment.