| Objective1.Clinical observationUlcerative colitis(UC)is a chronic inflammatory disease of the colon,patients with ulcerative colitis have an increased risk of colon cancer,suggesting exploration of novel therapeutic avenues may be useful.Jiaoqi powder(JQP)is Chinese traditional formula composed of Panax notoginseng and Donkey-hide gelatin.Clinical observation had shown that JQP has better clinical effect on promoting ulcer healing,reducing disease activity index and recurrence rate,which may be therapeutically beneficial for UC patients.By collecting and comparing the general data of ulcerative colitis patients in our hospital,the protective effect of JQP on intestinal mucosa injury was compared on the basis of routine treatment,so as to provide a clinical basis for further study.2.Experimental partBy utilizing network pharmacology methods,we collect the active compounds and corresponding targets of JQP and identify the therapeutic targets for UC treatment,as well as construct the network.In addition,the pharmacodynamics and molecular mechanism of JQP on ulcerative colitis were verified by mouse model.Based on the characteristics of multi-components and multi-targets of network pharmacology,the study provides a theoretical basis of the pathogenesis of ulcerative colitis and the mechanism of JQP from the aspects of attacking factors and protective factors.Methods1.Clinical observationThis study retrospectively analyzed and selected ulcerative colitis patients in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from January 1,2013 to December 31,2018,divided into observation group and control group.The observation group was treated with JQP on the basis of traditional Chinese and western medicine,while the control group was routinely treated with traditional Chinese and western medicine.31 cases in the observation group and 37 cases in the control group were selected.The clinical data of the patients were collected and the database was established.The records included gender,age,length of hospital stay,the symptoms and signs,results of lab examination and endoscopy,treatment prescription,etc.STATASE 15 and GraphPad Prism 5 were used for statistical analysis.Paired t test,rank sum test and chi-square analysis were used to compare the improvement of abdominal pain,diarrhea,and hematochezia between the observation group and the control group,as well as the Mayo scores before and after treatment and relapse condition.2.Experimental partThe study search for effective chemical constituents related to JQP by using TCMSP,BATMAN-TCM and TCMID databases,and the basic information of active compounds were retrieved by Pubchem and ZINC database.TCMSP,BATMAN-TCM,Swiss Target Prediction,STITCH and Target-Prediction,PharmMapper Server database were used to predict the therapeutic targets of the components of JQP.Then we obtain the UC potential targets through databases,text mining tools as well as GEO Dataset,and to construct the UC targets network.The interaction network of the known UC-related targets and predicted putative drug targets of JQP was intersected and constructed,and the core targets of the intersection PPI targets between JQP and UC were obtained by network topology.We also used Gene Ontology(GO)and KEGG pathway enrichment analysis to explore the JQP' s molecular mechanism of intestinal mucosal protection.Seventy-five male C57 mice weighing 25-30g were divided into 5 groups,including normal group,UC group,SASP group,JQP group and JQP+SASP group.The model was induced by sodium dextran sulfate(DSS).At the same time,JQP group,JQP+SASP group and SASP groups were given the drugs by gavage at the corresponding dose.After 7 days of oral administration,the body weight,DAI index and pathological changes of colon were evaluated.The mRNA expression of Tnf,116,I11b and Vegfa in colon tissue were detected.Results1.Clinical observation(1)The gender,age,course of disease,clinical type,extent and severity of disease of the observation and the control group,as well as Mayo scores,quantitative scores of TCM symptoms,abdominal pain,diarrhea,and hematochezia were no significant difference,which was comparable.(2)Compared with those before treatment,the average of Mayo scores in the observation and the control group after treatment was significantly lower(P<0.01),so as the quantitative scores of diarrhea,and hematochezia(P<0.01),the difference was statistically significant.While the quantitative scores of abdominal pain after treatment is lower than that before treatment in observation group(P<0.01),there is no significant difference between the quantitative scores of abdominal pain before and after the treatment in control group.Compared with the control group after treatment,the Mayo scores and quantitative scores of diarrhea and hematochezia in the observation group were significantly lower(P<0.01).(3)Chi square test showed that there was significant difference in recurrence type between the observation group and the control group(P<0.05).2.Experimental part(1)We collect 11 active compounds by utilizing network pharmacology methods,and the herb-active compound-putative target network of JQP with 11 compound-nodes and 925 target-nodes was constructed.(2)We collected 2104 UC related targets in the research,and intersected them with the potential targets of JQP,result shows JQP shared 207 putative targets with UC related targets.(3)JQP PPI target network contains 802 proteins,UC PPI target network contains 1423 proteins,184 major candidate targets were identified for JQP that are central to UC progression.69 core targets was shown in the network,including IL6,JUN,TP53,TNF,VEGFA,NFKB1,IL1B,etc.(4)Gene ontology enrichment analysis showed 89 terms including 67 biological process(BP),11 molecular function(MF)and 11 cellular component(CC)terms.(5)KEGG pathway enrichment analysis showed 51 signaling pathways were significantly associated with the targets,including TNF signaling pathway,HIF-1 signaling pathway,pathways in cancer,Inflammatory bowel disease,Colorectal cancer,VEGF signaling pathway.(6)Compared with the normal group,the mice in the UC group had severe colon tissue injury,the body weights and the colon length were significantly decreased(P<0.01),DAI scores and pathological score were significantly increased(P<0.01).Compared with the UC group,the body weights and the colon length in the JQP group,JQP+SASP group,SASP group were significantly increased(P<0.05),DAI scores(P<0.05)and pathological scores were significantly decreased(P<0.01).(7)Compared with the normal group,the mRNA expression of Tnf,116,11 1b in the UC group were significantly higher(P<0.01),meanwhile the Vegfa expression of mRNA in the UC group was significantly lower(P<0.01).Compared with the UC group,the mRNA expression of Tnf,I16,I11b in the JQP group,JQP+SASP group,SASP group were significantly lower(P<0.01),and the Vegfa expression of mRNA were significantly higher(P<0.01).Conclusion1.Clinical observationJQP has advantages in improving abdominal pain,diarrhea and hematochezia in patients with UC,indicating that it has protective effect on intestinal mucosa injury.Meanwhile,JQP can reduce the recurrence frequency of UC patients and prolong the clinical remission time.2.Experimental partThe research found that JQP could alleviate the pathological damage of the intestinal mucosa in UC mice,decrease the mRNA expression of Tnf,116,Illb in colon tissue,increase the mRNA expression of Vegfa in colon tissue and play a protective role in colon tissue of UC mice. |
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