| Objectives1 Based on the meta-analysis system to evaluate the effectiveness and safety of Coptis-Cinnamon in the treatment of T2DM patients,and provide the best evidence for the clinical treatment of Coptis-Cinnamon for T2DM patients.2 Excavate Professor Zhao Jinxi’s clinical experience in the treatment of T2DM patients with Coptis-Cinnamon,and conduct an inductive analysis from the clinical symptoms and drug compatibility of the patients,in order to provide reference and reference for the application of Coptis-Cinnamon in the clinical treatment of T2DM patients.3 To study the hypoglycemic mechanism of Coptis-Cinnamon on db/db mice,and explore its blood glucose-lowering mechanism and new targets from various aspects such as morphology,intestinal flora,and bile acid metabolism.Methods1 Retrieved to January 2021 about the clinical randomized controlled trial study of Coptis-cinnamon in the treatment of T2DM patients,independently screened by two researchers,methodological evaluation of the research literature data that meets the standard,using Revman 5.3 software provided by cochrane Data extraction of the included research literature and statistical analysis or descriptive analysis.2 Using the methods of descriptive analysis,association rules and cluster analysis,the collected medical records of 332 T2DM patients treated with Coptis-cinnamon by Professor Zhao Jinxi were studied,from the clinical symptoms,frequency of medication use,meridian of the drugs,and drug Efficacy,drug relevance,and different compatibility of drug clusters were analyzed,and Professor Zhao Jinxi’s clinical experience in the treatment of T2DM with Coptis-cinnamon was summarized.3 Diabetes model mice db/db mice and db/m mice were divided into blank group,control group,metformin group,coptis group,cinnamon group and coptis-cinnamon group.Study 1:Record and analyze the basic conditions of each group of mice,such as blood sugar,fasting insulin,body weight,etc.;use transmission electron microscope to observe the ultrastructure of the intestinal villi and intestinal tight junctions of the mice in each group.Study 2:Using 16s RNA high-throughput sequencing method to observe and analyze the different distribution and composition of the intestinal flora of mice in each group.Study 3:Using liquid chromatography(LC-MS)to analyze and explore the bile acid metabolism of mice in each group.Study 4:The RT-PCR method was used to detect and analyze the expression of TGR5 mRNA and GLP-1 mRNA in the ileum of each group of mice.Study 5:Using immunohistochemical method to analyze the expression of TGR5 protein and GLP-1 protein in the ileum of each group of mice.Results1 In the analysis of the clinical efficacy and safety of Coptis-cinnamon in the treatment of T2DM patients,a total of 89 articles were retrieved,and 6 articles were finally included,with a total of 562 patients.The analysis results showed that the total effective rate(RR=1.22,95%CI=1.11～1.34,P<0.0001)and sleep quality(SMD=-1.08,95%CI=-2.10～0.05)of T2DM patients in the Coptis-cinnamon intervention group,P=0.04)and the islet cell HOMA-P index(WMD=4.30,95%CI=3.18～5.42,P<0.00001)were significantly higher than the control group,in fasting blood glucose(WMD=-1.28,95%CI=-2.04～-0.53,P=0.0008),TCM syndrome score(SMD=-1.86,95%CI=-2.09～-1.63,P<0.00001)and 2h postprandial blood glucose(WMD=-2.33,95%CI=-2.59～-2.07,P<0.00001)was significantly lower than the control group,there was no significant difference in improving glycosylated hemoglobin,fasting insulin,triglyceride TG and cholesterol TC in T2DM patients with the control group.Among the included literature,only one article described the adverse reaction of a total of 40 people in the experimental group.The adverse reaction was gastrointestinal discomfort.There was 1 person in total,and the adverse reaction rate was 2.5%.2 A total of 332 patient cases were included in the clinical study.Among them,182 were male patients and 150 were female patients.The results of the descriptive analysis showed that among the included patients,the clinical symptoms of the top 10 patients included poor sleep,dry mouth,fatigue,backache,back pain,tinnitus,mouth bitter,cold legs,dizziness and dreaminess.The top 5 tongue and pulse conditions include dark red tongue,heavy pulse,muddy tongue,greasy coating and red tongue;The top 10 drugs used frequently include Coptis,Cinnamon,Danshen,Tangerine Peel,Pueraria lobata,Baishao,Huangqin,Fuling,Licorice and Pinellia.The top 5 meridians of drugs include the liver meridian,spleen meridian,lung meridian,kidney meridian and heart meridian.The results of cluster analysis showed that the drugs with the largest correlation coefficients included Coptis-cinnamon,lychee core-Digupi,tangerine peel-Fa Pinellia,Bupleurum-Huangqin,Chishao-Baishao,Chuanshanlong-Tufuling-Mianbixie,Angelica-Chuanxiong,Guij ianyu-N iubangzi Sangji sheng-Xuduan and Fuchaocangzhu-Fuchaobaizhu.Association rule analysis results show that the top 6 drug combinations with confidence include Chishao-Baishao,tangerine peel-Fuling-Huangqin,pueraria lobata root-digupi-Lizhihe,pueraria lobata root-Danshen-Baishao,Fuling-Chenpi-Fabanxia and chaocangzhu chaobaizhu,the top 6 confidence levels include backache Sangjisheng-Xuduan-Gouji;skin pruritus-Kushen-Difuzi;blurred vision-Sangye Juhua-Xiakucao;fingertip numbness and pain with Gouteng-Jixueteng-WeiLingxian,urine foam with Shiwei Chuanshanlong-Bixie;sexual dysfunction-Jiuxiangchong-Fengfang.3 Experimental study of the mechanism of Coptis-cinnamon on the hypoglycemic mechanism of db/db mice.Study 1:Study the basic conditions of blood sugar,body weight and small intestine ultrastructure of each group of mice.Compared with the model and metformin groups,the weight increase trend of the coptis group,cinnamon group and Coptis-cinnamon group slowed down.the weight loss trend of the Coptis-cinnamon group was the most obvious,the blood glucose of the normal group was significantly higher than that of the other groups(P<0.05),the blood glucose levels of mice in the metformin group,coptis group,cinnamon group and Coptis-cinnamon groups were significantly lower than the model group(P<0.05),coptis and Coptis-cinnamon groups is better than the cinnamon group(P<0.05),and there is no significant difference between the Coptis group and the Coptis-cinnamon group.The fasting insulin of the normal group was significantly lower than that of the other groups of mice(P<0.05).The fasting insulin of mice in the metformin group,the coptis group and the Coptis-cinnamon group was significantly lower than that of the model group(P<0.05),and the fasting insulin of the three groups was significantly lower than that of the model group(P<0.05).The average fasting insulin in the cinnamon group was the lowest but not statistically significant(P>0.05).The observation results under transmission electron microscope showed that the intestinal mucosa epidermal microvilli of the normal group were arranged uniformly and neatly,with clear borders,uniform length,no irregular shedding,no obvious changes in cells,uniform intercellular space,and normal size,the intestinal mucosal epidermis of the model group.The microvilli are sparsely arranged,the boundary is not clear,the length is different,the shape is irregular,there is a phenomenon of shedding and fusion,the tight junction gap between the intestinal mucosal epithelial cells is widened,and the structure is blurred;the intestinal mucosal structure of mice in the biguanide group and the three groups of Chinese medicine The microvilli are neatly arranged,normal in shape,uniform in size and tightly connected.The coptis-cinnamon group is arranged more closely and uniformly than the other two Chinese medicine groups and the biguanide group.The internal and external structures of the cells are more complete The intercellular space is uniform and the size is normal.The intestinal mucosa the closely connected ultrastructure is relatively complete,which is the closest to the normal groupStudy 2:Study on the differences in the distribution and composition of the intestinal flora of each group of mice.The difference of the intestinal flora of each group of mice was analyzed,and the results showed that the content of Bacteroides in the Coptidis-cinnamon group at the level of Phylum was significantly lower than that in the Coptidis,Cinnamon and Metformin groups.The abundance of Firmicutes in the cinnamon group was significantly decreased,which was lower than that of the normal group,model group and other drug groups;The Sobs index and Shannon index of the normal group and the Coptis-cinnamon group were lower than that of the model group,the Coptis-cinnamon group at the phylum level could increase the Proteobacteria,Verrucomicrobia and Chloroflexi Abundance(P<0.05);detection and analysis under Genus level classification showed that Akkermansia,Ruminococcus_gnavus_group,and Escherichia-Shigella in the Coptis-cinnamon group.The abundance of Parabacteroides was significantly higher than that of the model group(P<0.05);Under the OTU level classification,the OTU823,OTU782,OTU806,OTU716,OTU329,OTU839,OTU766,OTU109 in the Coptis-cinnamon group were significantly higher than the model group(P<0.05).Spearman correlation coefficient was used for model prediction and correlation analysis of samples.It was found that most of the colonies with higher bacterial abundance in the Coptis-cinnamon group than in the model group were negatively correlated with the blood sugar and body weight of db/db mice,such as Verrucomicrobia and Akkermania.Genus(Akkermansia)and OTU823,OTU782,etc.Study 3:Study on bile acid metabolism of mice in each groupThe bile acid metabolism of mice in each group was studied.The results showed that the content of cholic acid(CA)in the Coptis-cinnamon group and the cinnamon group was significantly higher than that of the normal group and the model group(P<0.05).Coptis-cinnamon group The content of chenodeoxy cholic acid(CDCA)was significantly higher than that of the model group(P<0.05),the Coptis-cinnamon group and Ursodeoxy cholic acid(UDCA)were significantly lower than that of the model group(P<0.05),the Coptis-cinnamon group was significantly lower than the metformin group(P<0.05).Study 4:Study on the expression of TGR5 mRNA and GLP-1 mRNA in the small intestine of each group of mice.Detection and analysis of the expression of TGR5 mRNA in the intestines of mice in each group showed that the expression of TGR5 mRNA in the model group was lower than that of the blank group,but it was not statistically significant(P>0.05),the expression of TGR5 mRNA in the model group was significantly lower than that of the Coptis-cinnamon group(P<0.05),the expression of TGR5 mRNA in the Coptidis group was significantly lower than that of the Coptidis-cinnamon group(P<0.05),the expression of TGR5 mRNA in the cinnamon group and Coptis-cinnamon group was higher than that of the metformin group,but Not statistically significant(P>0.05).The GLP-1 mRNA expression in the intestines of the mice in each group was detected and analyzed.The results showed that the GLP-1 mRNA expression in the model group was significantly lower than that in the normal group(P<0.05),the GLP-1 mRNA expression in the Coptidis-cinnamon group was significantly higher than in the model and coptis gorups.Coptis-cinnamon group was higher than that of the metformin group,but there was no statistical difference(P>0.05).Study 5:Study on the expression of TGR5 protein and GLP-1 protein in the small intestine of each group of mice.The intestinal TGR5 protein expression of mice in each group was detected and analyzed.The results showed that the intestinal TGR5 protein expression of mice in the model group was significantly lower than that of the blank group(P<0.05).The expression of TGR5 protein in the intestine of mice in the Coptis-cinnamon group was significantly higher than that in the metformin and coptis groups(P<0.05).The GLP-1 protein expression in the intestines of mice in each group was detected and analyzed.The results showed that the expression of GLP-1 protein in the intestine of mice in the model group was lower than that of the blank group,but it was not statistically significant(P>0.05).The expression of GLP-1 protein in mouse intestine was significantly higher than that in the model group(P<0.05),the other groups had no significant statistical significanceConclusion1 The results of the system evaluation based on the meta-analysis system show that Coptidis-cinnamon has significant clinical efficacy in the treatment of T2DM,which can effectively reduce the fasting blood glucose,clinical syndrome scores,and improve the HOMA-β index of insulin function in patients with T2DM in the clinic.2 Clinical research results show that in T2DM patients treated with Coptidis-cinnamon by Professor Zhao Jinxi,the tongue and pulse condition is mostly heat,but there are also symptoms of coldness in the lower limbs,chills and fear of cold,and there are upper heat and lower cold or a mixture of cold and heat.Taking Coptis-Cinnamon as the center,adopting different compatibility for different patients,different clinical symptoms and different T2DM complications,such as diabetic nephropathy patients with symptoms of urinary foam,using Coptis-Cinnamon and Tufuling-Mianbixie-Chuanshanlong;peripheral neuropathy patients have fingertips numbness and pain symptoms,using Coptis-cinnamon combined with Jixueteng Gouteng-Weilingxian,etc.;patients with diabetic retinopathy have symptoms of blurred vision,using Coptis-cinnamon combined with Sangye-Juhua-Xiakucao to clear liver and improve eyesight3 Experimental results show that Coptis-cinnamon can lower glucose levels of db/db mice.May be related to Coptis-cinnamon can delay the weight gain of db/db mice,reduce their fasting insulin and repair the intestinal barrier state of db/db mice.It also regulates the type and distribution of the intestinal flora of db/db mice,regulates the secretion of bile acids in db/db mice,and increases the expression of TGR5 mRNA,GLP-1 mRNA,TGR5 protein and GLP-1 protein in the small intestine. |
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