ABSTRACT
Two terpenes, 3-keto-tirucalla-8,24-dien-21-oic acid(KTDA) and 2-methoxy-5-acetoxy-furanogermacr-1(10)-en-6-one(FSA), are isolated from Olibanum and Myrrha respectively, which are characterized by high yield and easy crystallization during the preparation. The present study explored the regulatory targets and anti-inflammatory mechanism of KTDA and FSA based on network pharmacology and cell viability assay. First, the drug-likeness of KTDA and FSA was predicted by Swiss ADME. The target prediction of active components was carried out by Swiss Target Prediction and Pharmmapper. TTD, Drug Bank, and Gene Cards were searched for inflammation-related target genes of KTDA and FSA. Protein-protein interaction(PPI) analysis was performed on the inflammatory targets of KTDA and FSA by STRING, and Cytoscape was used to conduct topological analysis of the interaction results and construct the PPI network. GO function and KEGG pathway enrichment analyses of inflammatory targets of KTDA and FSA were carried out by DAVID, and a " component-target-pathway" network was constructed. Finally, lipopolysaccharide(LPS)-induced RAW264. 7 cells were treated with KTDA and FSA at different concentrations, and nitric oxide(NO) concentration and protein and m RNA expression levels were detected. The results showed that both KTDA and FSA showed good drug-likeness. A total of 157 and 142 inflammation-related targets of KTDA and FSA were screened out. PPI network analysis showed that MAPK1, AKT1, MAPK8, PIK3 CA,PIK3 R1, EGFR, etc. might be the key proteins for the anti-inflammatory effect. PI3 K/AKT and MAPK signaling pathways were obtained by KEGG and GO-BP enrichment. Cell experiment results showed that KTDA and FSA could exert anti-inflammatory effects by inhibiting NO production, reducing the phosphorylation levels of JNK, p38, and AKT proteins, and down-regulating the m RNA expression of interleukin(IL)-1β and IL-6. Meanwhile, FSA could also inhibit ERK phosphorylation. The results indicated that KTDA and FSA had significant anti-inflammatory activity, which provided a scientific basis and important support for the further research,development, and utilization of Olibanum and Myrrha.
Subject(s)
Animals , Ants , Drugs, Chinese Herbal/pharmacology , Frankincense , Lipopolysaccharides , Molecular Docking Simulation , Network PharmacologyABSTRACT
Objective: To construct the “active components-inflammatory target-anti-inflammatory pathway” network of Zanthoxylum nitidum intervened in inflammation, and predict the target of Z. nitidum intervened in inflammation and its anti-inflammatory mechanism. Methods: Using domestic and foreign literatures, TCMSP database, Pharmmapper server, oral availability (OB), and pharmacodynamics (DL) as the limiting conditions, the components of Z. nitidum were screened and the relative targets were predicted and collected. OMIM database was used to screen inflammation-related genes and protein targets; The STRING database was used to construct the interactive network between inflammatory targets; The network file of “active ingredient-predictive target-inflammatory target” was obtained by PPI analysis and imported into Cytoscape 3.5.1 software to construct the network of “active ingredient- inflammatory target”, so as to obtain the targets directly related to the anti-inflammatory effects of Z. nitidum. DAVID database was used to enrich the KEGG pathway of the selected targets, and then ClueGO plug-in was used to analyze the biological function of the target involved. Finally, the “active component-inflammatory target-anti-inflammatory pathway” network was constructed by combining the above relationships. Results: Twenty-three active ingredients were screened, and nine core anti-inflammatory targets were identified as COX-2, iNOS, PPARG, COX1, MAPK-14, JUN, NR3C1 and so on; The most critical pathways included TNF TRLs signaling pathways. Conclusion: It is preliminarily revealed that the anti-inflammatory effect of Z. nitidum is achieved through the interaction of multiple components and multiple targets, regulating the joint intervention of multiple pathways. However, the key targets and specific regulatory mechanisms need to be explored and verified by further experimental studies.
ABSTRACT
OBJECTIVE： To predict the anti-inflammatory active components and mechanism of couplet medicine of Notopterygium incisum-Angelica pubescens. METHODS： According to the principle of oral bioavailability≥30％ and drug- likeness≥0.18， active components of N. incisum and A. pubescens were screened； TCMSP was used to predict and screen the potential target of them. Using “Anti-inflammatory” as keyword， inflammatory related target genes were retrieved from human gene database Genecards. Common target was screened by mapping the target genes of active ingredients from couplet medicine of N. incisum-A. pubescens. The active ingredient-target network was established by using Cytoscape 3.5.1 software. The screened targets were used to construct the target protein interaction （PPI） network on the STRING V 10.5 platform. Its anti-inflammatory mechanism was studied by KEGG signaling pathway and GO biological enrichment analysis. RESULTS： Totally 15 active components such as coumarin， beta-sitosterol， ammidin， nodakenin were selected from couplet medicine of N. incisum-A. pubescens. Acting on 49 targets such as transcription factor AP-1， PI3-kinase subunit gamma， estrogen receptor， they mainly involved 19 signaling pathways such as hepatitis B and cell apoptosis， and were involved in 47 biological processes such as regulating inflammatory response and prostaglandin biosynthesis. CONCLUSIONS： The anti-inflammatory mechanism of active components of couplet medicine of N. incisum-A. pubescens on multi-target， multi-channel and multi-biological processes is predicted， and it points out the direction for further anti-inflammatory mechanism study.
ABSTRACT
Objective: To study the anti-inflammatory effect and mechanism of Gutong plasters in acute inflammatory model of rats. Methods:Totally 60 SD rats were randomly divided into the blank group,the model group,Gutong plasters at low,medium and high dose groups(0.594,1.188 and 2.376 g/patch containing crude drug 0.48,0.96 and 1.92 g,respectively) and prednisone ace-tate group(0.005 4 g·kg-1). The acute inflammation model was prepared by injecting 5% formaldehyde into right side of foot plan-tar. And then,the anti-inflammatory effect was evaluated by measuring the foot plantar volume. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of nitric oxide(NO),histamine(HIS) and 5-hydroxytryptamine(5-HT) in serum and inflam-matory tissue,the levels of prostaglandin E2(PGE2),tumor necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β) and interleu-kin 6 (IL-6) in inflammatory tissue were also determined. Pathological changes were observed through the pathological sections pre-pared by HE staining. Results:When compared with the model group,Gutong plasters could significantly inhibit the swelling of foot plantar in inflammatory rats(P<0.01). At the same time,Gutong plasters could significantly reduce the levels of NO,5-HT and HIS in serum and inflammatory tissue in different degrees(P<0.05 or P<0.01),significantly reduce the content of PGE2in inflammatory tissue (P<0.05 or P<0.01),increase the content of IL-6 in inflammatory tissue and improve the pathological changes of inflammato-ry tissues (the pathological score was significantly reduced). In partical indictor changes,Gutong plasters and prednisone acetate showed an equal effect.In addition,Gutong plasters didn't show significant dose-dependent manner in inhibiting foot swelling,affect-ing inflammatory mediators and improving pathological changes(P>0.05). Conclusion:Gutong plasters have better anti-inflammato-ry effect in the acute inflammation model induced by formaldehyde in rats. The anti-inflammatory effect may be associated with the de-crease of the levels of NO,5-HT and HIS in serum and inflammatory tissue,the decrease of the content of PGE2and the increase of the content of IL-6 in inflammatory tissue. In addition,the anti-inflammatory effect may be relevant to improving the local inflammatory tis-sue subcutaneous edema and inflammatory cell infiltration.
ABSTRACT
To isolate corynoline from Corydalis bungeana Turcz.and study its anti-inflammatory mechanism via TLRs/NF-κB signal pathway.Corynoline was extracted by 80％ ethanol and purified by silicagel column chromatography.The structure and purity of corynoline was determined by UPLC,MS,1H NMR and 13C NMR.In the course of experiment,the cytotoxicity of corynoline was evaluated by MTT assay.And the inflammation model was established by RAW264.7 macrophages induced by lipopolysaccharide(LPS),which was intervened by coryno line.The expression levels of TLR4,TLR2 and nuclear transcription factor-κB(NF-κB) signaling pathways related proteinsin RAW264.7 macrophages were detected by Western blot.Furthermore,the expressionof NF-κB p65 mRNA and nuclear p65 were determined by the real-time fluorescence quantitative PCR(RT-qPCR) and Western blot.Results showed that 5-40 μmol/L corynoline reduced the expression level of TLR4 and TLR2,and inhibited the phosphorylation level of IκBα and the phosphorylation and nuclear translocation of p65 at gene and protein levelin a dose-dependent manner in LPS-induced RAW264.7 cells.This study indicated the protective effect of corynoline on LPS-induced RAW264.7 macrophages may be related with the inhibition of TLRs/NF-κB inflammatory signaling pathway.
ABSTRACT
Inflammation is one of the important risk factors of rheumatic diseases. Aconiti Radix is widely used for the treatment of rheumatism, which has significant anti-inflammatory effects. However, its anti-inflammatory mechanism on molecular level is still not clear. The purpose of this study is to illuminate the anti-inflammatory mechanism of Aconiti Radix based on the protein interaction network (PIN) analysis on molecular network level. The main anti-inflammatory components (aconitine, hypaconitine and mesaconitine) were chosen in this study to obtain the targets of the components and protein-protein information though databases retrieval and construct the PIN of Aconiti Radix. By a graph theoretic clustering algorithm molecular complex detection(MCODE), 13 modules were identified and analyzed by gene ontology(GO) enrichment. The results showed that the anti-inflammatory mechanism of Aconiti Radix was mainly associated with prostanoid metabolic process and leukocyte chemotaxis mediated by chemokines. In this study, the anti-inflammatory mechanism of Aconiti Radix was elucidated systematically from molecular network level, which provided the scientific basis for the treatment of rheumatic diseases.
ABSTRACT
[Objective] To explore the anti-inflammatory effects of emodin and its therapeutic effect on acute lung injury. [Methods] By means of analyzing the relevant literatures in PUBMED,CNKI,CBM,Wanfang and Vip Da-tabase from 1998 to 2012,summarized the anti-inflammatory effects and mecha-nisms of emodin, as wel as its therapeutic effect on acute lung injury. [Results] A variety of studies have confirmed the anti-inflammatory effects of emodin, whose mechanism is related to emodin inhibiting the activation of NF-kappa B,modulaing various inflammatory factors, etc. In addition, the effect of emodin in the treatment of acute lung injury has been confirmed on celland animal levels. [Conclusion] Emodin has good prospect of clinical application.