Network pharmacology and molecular docking reveal zedoary turmeric-trisomes in Inflammatory bowel disease with intestinal fibrosis

BACKGROUND Inflammatory bowel disease(IBD) is a complex chronic IBD that is closely associated with risk factors such as environment, diet, medications and lifestyle that may influence the host microbiome or immune response to antigens. At present, with the increasing incidence of IBD worldwide, it is of great significance to further study the pathogenesis of IBD and seek new therapeutic targets. Traditional Chinese medicine(TCM) treatment of diseases is characterized by multiple approaches and multiple targets and has a long history of clinical application in China. The mechanism underlying the effect of zedoary turmerictrisomes on inducing mucosal healing in IBD is not clear.AIM To explore the effective components and potential mechanism of zedoary turmeric-trisomes in the treatment of IBD with intestinal fibrosis using network pharmacology and molecular docking techniques.METHODS The chemical constituents and targets of Rhizoma zedoary and Rhizoma sanarum were screened using the TCMSP database. The GeneCards database was searched to identify targets associated with intestinal fibrosis in IBD. The intersection of chemical component targets and disease targets was obtained using the Venny 2.1 online analysis platform, and the common targets were imported into the STRING 11.0 database to construct a protein interaction regulatory network. A “zedoary turmeric-trisomes-chemical composition-target-disease” network diagram was subsequently constructed using Cytoscape 3.7.2 software, and the topological properties of the network were analyzed using the “Network Analysis” plug-in. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the common targets were performed using the DAVID 6.8 database to elucidate the mechanism of zedoary turmeric-trisomes in the treatment of IBD. Subsequently, molecular docking of the compounds and targets with the highest intermediate values in the “zedoary turmeric-trisomes-chemical composition-target-disease” network was performed using Sybyl-x 2.1.1 software.RESULTS A total of 5 chemical components with 60 targets were identified, as well as 3153 targets related to IBD and 44 common targets. The protein-protein interaction network showed that the core therapeutic targets included JUN, MAPK14, CASP3, AR, and PTGS2. The GO enrichment analysis identified 759 items, and the KEGG enrichment analysis yielded 52 items, including the cancer pathway, neuroactive ligand-receptor interaction, hepatitis B, and the calcium signaling pathway, reflecting the complex biological processes of the multicomponent, multitarget and multipathway treatment of diseases with zedoary turmeric-trisomes. Molecular docking showed that the compound bonded with the target through hydrogen bond interactions and exhibited good docking activity.CONCLUSION This study identified the potential mechanism of action of zedoary turmeric-trisomes in the treatment of inflammatory bowel fibrosis using network pharmacology and molecular docking technology, providing a scientific basis for further expansion of their clinical use.

Long-Term Effect of Stent Coating with Zedoary Essential Components on Neointimal Formation in the Porcine Coronary Artery

Objective： To examine the effect of the zedoary essential component-eluting stent （ZES） on a porcine coronary neointimal formation. Methods： ZES, sirolimus-eluting stents （SES）, and bare metal stents （BMS） were randomly implanted in three different major epicardial vessels in 36 balloon-injured pigs. Coronary angiography, optical coherence tomography, and histomorphological analysis were used to determine antihyperpiasia effects. Results： ZES and SES had a significantly larger lumen diameter and area, and reduced diameter and area of stenosis in arteries at 30 and 90 days compared with arteries implanted with BMS （P〈0.01）. Histomorphometric analysis showed moderate inflammatory responses, such as infiltration of mononuclear cells, lymphocytes, and multinucleated giant cells in some arteries with SES compared with ZES （P〈0.05）. Injury scores were not different among the three groups at 30 and 90 days. The endothelialization score in the SES group was 2.69± 0.42 at 30 days and 2.83 ± 0.39 at 90 days compared with the ZES and BMS groups （both were 3.00 ± 0.00 at either 30 or 90 days, P〈0.05）. Well developed endotheiium was observed in the ZES group, while incomplete endothelium and inflammatory cells were observed with stent struts partly naked at the vessel lumen in the SES group. Conclusion： The ZES inhibits neointimal hyperplasia with good endothelia coverage in the porcine balloon injury coronary model.

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric(Curcumae Rhizoma,Ezhu in Chinese)has a long history of application and has great potential in the treatment of liver cancer.The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances.In order to clarify the specific mechanism of zedoary tumeric against liver cancer,this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer,and then verifies the joint anti liver cancer mechanism of its“pharmacodynamic group”.By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years,we found that pharmacodynamic substances,including curcumol,zedoarondiol,curcumenol,curzerenone,curdione,curcumin,germacrone,β-elemene,can act on multi-target and multi-channel to play an antihepatoma role.For example,curcumin can regulate miR,GLO1,CD133,VEGF,YAP,LIN28B,GPR81,HCAR-1,P53 and PI3K/Akt/mTOR,HSP70/TLR4 and NF-κB.Wnt/TGF/EMT,Nrf2/Keap1,JAK/STAT and other pathways play an antihepatoma role.Network pharmacological analysis showed that the core targets of the“pharmacodynamic group”for anti-life cancer are AKT1,EGFR,MAPK8,etc,and the core pathways are neuroactive live receiver interaction,nitrogen metabolism,HIF-1 signaling pathway,etc.At the same time,by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and“pharmacodynamic group”,it is found that they have great reference significance in target,pathway,biological function,determination of core pharmacodynamic components,formation of core target protein interaction,in-depth research of single pharmacodynamic substance,increasing curative effect and so on.By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and“pharmacodynamic group”in the treatment of liver cancer,this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and“pharmacodynamic group”.

Study on Treatment of Primary Hepatic Carcinoma by Arterial Perfusion Embolization with Zedoary Turmeric Oil

To evaluate the effect, side-effect and prospect of hepatic arterial perfusion embolization (HAPE) with Zedoary turmeric oil (ZTO) in treating primary hepatic carcinoma (PHC).Methods: Clinical study was carried out by administration of 1-3 ml ZTO through arterial catheter to induce embolism in 32 patients of PHC, and compared with 32 patients treated by hepatic arterial perfusion embolization with chemical agents (HAPE-C) in the control group. The Chinese herbal medicine was given orally to both groups according to Syndrome Differentiation of TCM. In the experimental study, transplantation hepatic carcinoma model was established in 40 rats. They were randomly divided into the treated group and the control group, 20 in each group, and were perfused with 10 mg/kg ZTO and 0.2-0.3 ml normal saline respectively to observe the effect of treatment.Results: The effect of treatment in the ZTO group was CR in 1 case and PR in 13 cases, the total effective rate being 43.75%, with AFP negative reversed in 7 cases, titer decreased in 7; while in the control group it was PR in 10 cases, the total effective rate being 31.25%, AFP negative reversed in 5, titer decreased in 2, and the difference of therapeutic effect between the two groups was insignificant (P>0.05). The post-perfusion thrombotic syndrome occurrence, with the symptoms of fever, abdominal pain, vomiting, etc. in the two groups was similar, but no bone marrow inhibition occurred in the ZTO group, which was different from the control group (P<0.01, P<0.05). The mean survival time, median survival time, 1-, 2-, 3- and 4-year survival rate in the ZTO group was 13.84 months, 10 months, 37.5%, 18.87%, 9.70% and 6.4% respectively, and in the control group, 8.03 months, 6 months, 15.6%, 6.27%, 0% and 0% respectively, the mean survival time, median survival time and 1-year survival rate in the ZTO group were significantly superior to those in the control group (P<0.05). Experimental study showed that the effect in the treated group was better than that in the control group in tumor growth inhibition with the tumor growth rate as 10.8±4.5%% vs 20.6±12.7%, P<0.05, tumor necrosis degree (P<0.01) and survival time prolonged (14.8±3.4 days vs 11.7±1.9 days, P<0.05).Conclusion: HAPE-ZTO in treating PHC showed the therapeutic effect similar to that of HAPE-C, but superior to the latter in survival time prolongation and bone marrow inhibition.

Effect of zedoary turmeric oil on the expressions of MHC-I antigen presentation pathway associated genes in cervical cancer cells

Objective To observe the effect of zedoary turmeric oil on the proliferation of cervical cancer cells Hela andthe expression of major histocompatibility complex classⅠ(MHC-Ⅰ) presentation pathway related genes in vitro,so as to provide experimental evidence for its application in the treatment of cervical high-risk human papilloma virus (HPV) infection.