Prescription and medication rules of traditional Chinese medicine for prevention and treatment of diabetic microangiopathy based on literature mining / 中国中药杂志

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

Effects of traditional Chinese exercises on blood glucose and hemoglobin A1c levels in patients with prediabetes: A systematic review and meta-analysis / 中西医结合学报

BACKGROUND@#Traditional Chinese exercises (TCEs) have a positive effect on glycemic control and hemoglobin A1c (HbA1c), but there is no consensus on the benefits of TCEs for patients with prediabetes.@*OBJECTIVE@#The objective of this study was to systematically investigate the effects of TCEs on blood glucose control in patients with prediabetes.@*SEARCH STRATEGY@#Comprehensive retrieval of randomized controlled trials (RCTs) was carried out using PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Data Knowledge Service Platform, China Biology Medicine disc, Google Scholar and Baidu academic databases. The retrieval window ranged from the establishment of the database to December 2018, and references related to the included trials were searched without language restrictions.@*INCLUSION CRITERIA@#The study included RCTs with a clinical diagnosis of prediabetes that was also treated with TCEs.@*DATA EXTRACTION AND ANALYSIS@#Literature screening, data extraction and literature quality assessment were performed independently by two researchers. In the case of disagreement, a third party was invited to negotiate and make a decision. Standardized mean difference (SMD) was used to estimate the therapeutic effect. Meta-analysis was performed using Review Manager 5.3.5 and Stata 15.0. Heterogeneity was assessed using Q test and I, and the source of heterogeneity was determined using Galbraith diagram and sensitivity analysis. A Q test resulting in P  50% indicated significant difference and random effect model analysis was performed. Otherwise, a fixed effect model was applied. Begg's and Egger's tests were used to assess publication bias.@*RESULTS@#Nine RCTs involving 485 participants were included in this study. The results showed that TCEs could reduce fasting blood glucose (FBG), 2 h blood glucose (2hPBG) and HbA1c in patients with prediabetes. The treatment subgroup showed that an intervention of 6 months had better results, while the Gongfa subgroup showed that the TCE Baduanjin yielded better results. (1) FBG: SMD = -0.73, 95% confidence interval (CI) [-0.97, -0.50], P < 0.00001; Baduanjin: SMD = -0.83, 95% CI [-1.13, -0.53], P < 0.00001; 6 month treatment: SMD = -0.73, 95% CI [-1.20, -0.26], P = 0.002. (2) 2hPBG: SMD = -0.75, 95% CI [-0.94, -0.57], P < 0.00001; Baduanjin: SMD = -0.62, 95% CI [-0.91, -0.32], P < 0.00001; 6 month treatment: SMD = -0.91, 95% CI [-1.39, -0.44], P = 0.0002. (3) HbA1c: SMD = -0.56, 95% CI [-0.89, -0.23], P = 0.00008; Baduanjin: SMD = -0.46, 95% CI [-0.83, -0.08], P = 0.02; 6 month treatment: SMD = -0.77, 95% CI [-1.24, -0.29], P = 0.002.@*CONCLUSION@#TCEs had positive effects in improving blood glucose levels in patients with prediabetes. Hence, TCEs may be of potential therapeutic value for patients with prediabetes, as an adjuvant therapy along with other treatments. Although the evidence suggests that the intervention is effective for 6 months, the mechanism of TCEs on glycemic control, the minimum exercise dose and their safety remain to be further studied.

Effect of Biling Qutong Prescription on SIRT3 Protein Expression and URAT1 mRNA in Skeletal Muscle of Diabetic Gout Rats / 中国实验方剂学杂志

Objective: To observe the effect of phlegm and blood stasis on the expressions of sirtuin 3(SIRT3)protein and urate transporter 1(URAT1) mRNA in skeletal muscle of diabetic rats with gout. Method: The 40 healthy rats, excepting the normal group, the remaining groups were fed with high-fat diet combined with low-dose streptozotocin solution (40 mg·kg-1) once a day, with blood glucose "16.7 mmol·L-1" as the criterion for the diabetes model. After 4 days, the 5% sodium urate solution was injected into the joint cavity once to induce the gout model. After the successful modeling, the Biling group (10 g·kg-1), the indomethacin group (5 mg·kg-1) and the pioglitazone group (10 mg·kg-1) continued to be administered for 21 days. The normal group and the model group were given the same amount of normal saline. The expression of SIRT3 protein in skeletal muscle tissue was determined by Western blot, URAT1 mRNA expression in bone tissue was detected by quantitative real-time fluorescence polymerase chain reaction(Real-time PCR),and blood was collected to measure blood glucose (GLU), blood uric acid (UA) and C-reactive protein (CRP). Result: Compared with the normal group, GLU, UA and CRP in the model group were significantly increased (PPPPPPPPConclusion: Biling Qutong prescription with effects in purging turbidity, detoxifying and dredging collaterals can significantly reduce the content of serum inflammatory factor CRP, significantly increase the protein expression of SIRT3 in skeletal muscle tissue of model rats, lower the content of URAT1 mRNA, reduce the blood glucose and blood uric acid levels in diabetic gout rats, and protect joints.

Mechanism of Danzhi Jiangtang Capsules on improving liver injury in hyperlipidemia rats based on MAPK pathway / 中国中药杂志

This study aimed to investigate the protective effect and preliminary mechanism of Danzhi Jiangtang Capsules( DJC) on liver of hyperlipidemic rats. The hyperlipidemia models were successfully made by high-fat diet for 12 weeks in male SD rats,and then divided into model control group and DJC treatment groups( 500 and 1 000 mg·kg~(-1)·d-1) via gavage administration for additional 8 weeks.The levels of serum lipid and liver metabolism indices were detected; HE and oil red O staining were used to observe the pathological changes of liver. Expression levels of extracellular regulated protein kinase 1/2( ERK1/2),c-Jun N-terminal kinase( JNK),and p38 mitogen-activated protein kinase( p38 MAPK) were detected by real-time polymerase chain reaction( RT-PCR). Expression of MCP-1,phosphorylated ERK( p-ERK),phosphorylated JNK( p-JNK),and phosphorylated p38 MAPK( p-p38) were analyzed by immunohistochemistry and Western blot. The results showed that DJC decreased body weight and serum levels of total cholesterol( TC),triglyceride( TG),alanine aminotransferase( ALT),aspartate aminotransferase( AST),increased serum high-density lipoprotein cholesterol( HDL-C) level,ameliorate injury and lipid deposition in the liver induced by the high-fat diet,decreased mRNA expression of ERK1/2,JNK and p-38 MAPK as well as protein expression of p-ERK,p-JNK,p-p38,and MCP-1,somewhat showing a dose-dependent effect. Therefore,DJC has an obvious protective effect on liver of hyperlipidemic rats with certain dose-dependent effect,and the mechanism may be related with inhibiting MAPK pathways and inflammation.

Experimental study on effect and mechanism of Danzhi Jiangtang Capsules on diabetic myocardial injury / 中国中药杂志

Diabetic cardiomyopathy( DCM) is one of the major cardiovascular complications of diabetes mellitus. Based on the clinical efficacy of Danzhi Jiangtang Capsules( DJC) in the prevention and treatment of diabetes and its cardiovascular complications,both in vivo and in vitro methods were adopted to investigate its effect and underlying mechanism of protecting myocardial injury induced by diabetes. The type 2 diabetic rats were prepared by feeding high-energy food combined with streptozotin( STZ) injection,and the effects of DJC were observed by blood sugar,blood lipid,hemodynamic index,cardiac weight index and the change of cardiac pathological morphology. The protein expressions of TLR4,MyD88 and NF-κB p65 in myocardial tissue were detected and the possible mechanism was preliminarily analyzed. Besides this,DJC containing serum was prepared,H9 c2 cardiomyocyte induced by high sugar were studied to investigate the mechanism of TLR4/MyD88/NF-κB signaling pathway regulating cardiomyocyte injury and the therapeutic effect of DJC. The results demonstrated that fasting blood sugar,glycosylated hemoglobin,total cholesterol and glycerol triglyceride were significantly reduced( P<0. 01,P<0. 05). Cardiac weight index,left ventricle weight index,LVEDP and the protein expressions of TLR4,MyD88 and NF-κB p65 were significantly reduced( P<0. 01,P<0. 05). LVSP,+dp/dtmaxand-dp/dtmaxincreased significantly( P<0. 01,P< 0. 05). Moreover,the pathological damage of myocardial tissue in rats improved significantly. Meanwhile,the protein expressions of TLR4,MyD88 and NF-κB p65 in cardiomyocytes induced by high sugar were significantly inhibited( P<0. 01).It showed that DJC were effective in preventing and treating myocardial injury induced by diabetes and its mechanism may be related to the over-expression of TLR4/MyD88/NF-κB signaling pathway induced by high sugar.

Mechanism of Danzhi Jiangtang Capsules in treatment of diabetic macrovascular disease in GK rats based on correlation between microRNAs and inflammatory factors / 中国中药杂志

This study was aimed to investigate the mechanism of Danzhi Jiangtang Capsules( DJC) in the treatment of diabetic macrovascular disease in Goto-Kakizaki( GK) rats. The diabetic macrovascular disease rat model was induced by feeding high-fat and high-sugar combined with endothelial nitric oxide synthase( NOS) inhibitor N-nitro-L-arginine methyl ester( L-NAME)( 0. 1 g·L-1·d-1). According to the random array table,the model rats were randomly divided into the model group,DJC groups( 1 260,630,320 mg·kg-1),atorvastatin group( 105 mg·kg-1) and metformin group( 10 mg·kg-1),with 12 rats in each group. The rats received gavage administration for 8 weeks. Twelve Wistar rats were selected as the normal control group. The changes of body weight,water intake,blood glucose,plasma total cholesterol( TC),triglyceride( TG),high density lipoprotein( HDL-C),low density lipoprotein( LDL-C),interleukin( IL-1β),IL-6,tumor necrosis factor( TNF-α),nitric oxide( NO),endothelin( ET-1) were observed in these rats. Aortic tissue was taken and the pathological changes were observed by HE staining. RT-PCR was used to detect the mRNA levels of IL-1β,IL-6,and TNF-α in rat aorta. RT-PCR of the stem loop was used to detect the levels of miRNA-126,miRNA-155,miRNA-146 a,and miRNA-21 in rat plasma and aortic tissue. The canonical correlation between miRNAs and inflammatory factors was then analyzed. The results showed that DJC increased the rat body weight,lowered water intake,reduced the random blood glucose,reversed the rat aorta tissue damage,reduced serum TC,TG,LDL-C,ET-1,IL-1β,IL-6,TNF-α,as well as miRNA-155,miRNA-146 a and miRNA-21 levels in serum,elevated plasma HDL-C,NO content,reduced the aorta mRNA of IL-1β,IL-6,TNF-α,and the miRNA-155,miRNA-146 a and miRNA-21,elevated miRNA-126 expression in aorta. Aortic miRNA-126,miRNA-155,miRNA-146 a and miRNA-21 expression levels were typically correlated with the expression of inflammatory factors,among which miRNA-126 was negatively correlated,miRNA-155,miRNA-146 a and miRNA-21 were positively correlated with the factors. These results suggested that DJC had therapeutic effects on diabetic macrovascular diseases,and the mechanism of action may be related to the regulation of miRNA-126,miRNA-155,miRNA-146 a and miRNA-21 levels,as well as the reduction of inflammatory factors and vascular inflammatory response.

Effect of Huangdi Anxiao Capsules on zebrafish vascular lesions induced by high glucose and high fat / 中国中药杂志

Zebrafish of different strains with 5 dpf (5 days post-fertilization) were selected and fed with 0.2% high-fat diet for 8 h and 3% glucose solution for 16 halternatively during the day and night for 4 consecutive days. The zebrafish model was established and randomly divided into model group, Huangdi Anxiao Capsules (260 mg·L⁻¹) group and pioglitazone (32 mg·L⁻¹) group. The drug treatment groups were given the water-soluble drugs, with a volume of 25 mL, and incubated in a 28 °C incubator for 4 days. To detect the exposure to the corresponding drugs, the normal control group was set up. Thirty zebrafish were included in each group. The effect of Huangdi Anxiao Capsules on vascular wall thickness, fluorescence intensity of islet beta cells, fluorescence intensity of macrophages, and blood flow velocity of zebrafish were detected. The expressions of vascular endothelial growth factor (vegfaa) and angiotensin converting enzyme (ACE) were detected by RT-PCR. The results showed that compared with the model group, Huangdi Anxiao Capsules can significantly reduce the thickness of the blood vessel wall, increase the fluorescence intensity of islet β cells and macrophages, increase the blood flow velocity in vivo, and decrease the ACE and vegfaa expressions in zebrafish. It is suggested that Huangdi Anxiao Capsules may alleviate zebrafish vascular lesions by regulating the expressions of ACE and vegfaa.

Research advances on astragaloside-IV in treatment of diabetes mellitus and its complications pharmacological effects / 中国中药杂志

Diabetes has become a global public health problem that seriously threatens human health. Traditional Chinese medicine, the characteristics of the role of multiple targets, has a unique advantage in the prevention and treatment of diabetes mellitus and its complications. Astragaloside-Ⅳ (AS-Ⅳ), one of the main activities of Astragalus membranaceus, has a series of pharmacological effects including improvement in the function of endothelial cells and neovascularization, anti-inflammatory, antioxidant, regulating energy metabolism, protectionnervous, anti-cancer and so on. In this paper, AS-Ⅳ to prevent and treat diabetes and its complications has been reviewed, which has effect on lowering blood sugar, lowering blood pressure, improving insulin resistance, inhibiting inflammatory reaction and oxidative stress. Additionally, it also can improve the diabetic animal and cell model of diabetic vascular disease, diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy, diabetic cardiomyopathy and other pathological damages. AS-Ⅳ may be a potential active substance for the treatment of diabetes and its complications.

Effect of danzhi jiangtang capsule combined exercise on the protein expression of NADPH oxidase p22phox in pancreatic tissues of diabetic rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore effects of exercise combined Danzhi Jiangtang Capsule (DJC) on the protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox in pancreatic tissues of diabetic rats.</p><p><b>METHODS</b>Sixty male Wistar rats were injected with low dose of streptozotocin and fed with high fat diet to establish a diabetic rat model. The levels of p22phox and 8-hydroxy-2-de-oxyguanosine (8-OHdG) protein in pancreatic tissues were detected by immunohistochemical method, and the level of p22phox protein was also detected by Western blot in the normal group, the model group, the excise group, the DJC group, and the DJC +excise group, respectively.</p><p><b>RESULTS</b>The expression levels of p22phox and 8-OHdG protein in pancreatic tissues were significantly higher in the model group than in the normal group (P <0.01). p22phox and 8-OHdG were mainly expressed in the cytoplasm of pancreatic cells. After administration of exercise or DJC, the expression lev- els of p22phox or 8-OHdG protein in pancreatic tissues decreased significantly (P <0. 01). Exercise combined DJC had synergistic effects in decreasing expressions of p22phox and 8-OHdG (P <0.05).</p><p><b>CONCLUSION</b>Exercise, DJC, and exercise combined DJC could protect islet beta cells by decreasing the expression of NADPH oxidase in beta cells and reducing sources of oxidative stress.</p>

Effects of danzhi jiangtang Capsule combined exercise on pancreatic oxidative stress and islet beta-cell function in diabetic rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effects of Danzhi Jiangtang Capsule (DJC) and exercise on islet beta-cell function index (HOMA-% beta), blood glucose, and oxidative stress of diabetic rats.</p><p><b>METHODS</b>A diabetic rat model was established using low dose streptozotocin and high fat forage in 60 male Wistar rats. The effects of exercise, DJC, and DJC combined exercise on the serum levels of fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), as well as the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA) in the pancreatic tissue were observed. The HOMA-%beta was also calculated. The main factors that affecting HOMA-%beta were explored using multi-factor regression analysis.</p><p><b>RESULTS</b>Compared with model group, the levels of FBG, TG, TC, and pancreatic MDA were significantly reduced after intervention of exercise or DJC (P < 0.05, P < 0.01), while HOMA-% beta obviously increased (P < 0.01). The pancreatic GSH-Px activity significantly increased in the exercise group (P < 0.01). Exercise and DJC had synergistic effects on FBG, TG, HOMA-% beta, pancreatic SOD, and GSH-Px activities (P < 0.05). There was a negative and linear regression correlation between FBG and pancreatic SOD and GSHPx activities. HOMA-%beta was negatively correlated with FBG, TG, TC, and pancreatic MDA content, and positively correlated with SOD and GSH-Px activities. Besides, there was a linear regression correlation between HOMA-%beta and FBG.</p><p><b>CONCLUSION</b>Exercise and DJC played synergistic effects, could improve the glucose and lipid metabolisms and enhance antioxidant activities, thus relieving the injury of pancreatic beta cells.</p>

Effect of Danzhi Jiangtang Capsule on the Level of Blood Fat in Model Rats of Type 2 Diabetes Insuling Resistance / 中国中医药信息杂志

Objective To investigate the effect of Danzhijiangtang capsule on serum,fat in type 2 diabetic rats.Methods The model of type 2 diabetes mellitus rats were established by injecting small does streptozotocin(STZ)into abdomen and feeding high sucrose-fat diet.All the rats were divided randomly into five groups.The level of blood glucose,serum insulin,insulin sensitivity index,blood fat(triglyceride, cholesterol,high-density lipoprotein,low-density lipoprotein),free fatty acid after treated were examined. Results Danzhijiangtang capsule could decrease the level of blood fat.Conclusion Danzhijiangtang capsule could improve the blood fat in type 2 diabetic rats.