ABSTRACT
Objective: To observe the metabolic profile changes caused by Danzhi Jiangtang Capsule (DJC) in treatment of type 2 diabetic rats and to study the possible metabolism. Methods: All the SD rats involved in the experiment were randomly divided into normal control, model, and DJC groups. The rats in the model and DJC groups were fed on high-fat diet for 4 weeks after ip injection with a small dose of streptozotocin to copy type 2 diabetic rat model. After the modeling, the rats in the DJC group were ig administered with DJC (1.26 g/kg) for 4 weeks, and the blood glucose was monitored weekly. After the treatment, urine of rats was collected, then all the rats were sacrificed, abdominal aortic blood was taken to detect the levels of insulin (INS) and glycated hemoglobin (GHb) in plasma. Using UPLC/QTOF-MS with principal component analysis (PCA) to analyze the metabolic profile changes, the metabolites were identified by databases, and metabolism pathways were analyzed. Results: Blood glucose monitoring and INS, GHb testing results showed that DJC could lower blood sugar and elevate plasma INS level. In the positive and negative ion modes, we screened seven and six variability markers respectively. The variability markers were related to glucose metabolism, tyrosine metabolism tryptophan metabolism, and oxidative stress-related reactions. Conclusion: DJC can lower blood sugar, repair islet cells to cure the type 2 diabetes, and the possible mechanism may relate to the regulation of energy metabolism, tyrosine metabolism, tryptophan metabolism, and oxidative stress.
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OBJECTIVE: To investigate the nephroprotective effect of danzhi jiangtang capsule(DJC) on diabetic rats induced by streptozotocin(STZ) and elucidate its mechanism. METHODS: Model of diabetic rats were established by combination of high-fat diet-fed and low-dose STZ injection in SD rats. The successful models were chosen and randomly divided into model group, low-dose and high-dose of DJC(600, 2 000 mg · kg-1, ig) groups, each consisting of 8 rats. Control and model groups were administered equal volume of distilled water. After 8 weeks of treatment, the rats were killed and serum was separated to detect blood lipid, renal function and oxidative stress. The kidneys were weighed, and the renal indexes were calculated. Renal tissue specimens were fixed for HE and PAS staining; the expressions of JAK2, STAT3, p-JAK2, p-STAT3 in the kidneys were observed by Western blot; the renal inflammatory factors TNF-α, IL-6 and MCP-1 were detected by ELISA. RESULTS: Fasting blood glucose (FBG), blood lipid, renal index, oxidative stress of model group were significantly increased, renal function was reduced, and the morphology of renal tissue changed significantly. The renal inflammatory cytokine TNF-α, IL-6 and MCP-1 and the expressions of p-JAK2, p-STAT3 increased significantly in diabetes mellitus rats. After 8 weeks of treatment, blood lipid and oxidative stress in DJC groups were decreased, but there was no obvious difference in FBG between DJC groups and model group, the renal function and the pathological changes of renal tissue were improved obviously. The expressions of inflammatory cytokine(TNF-α, IL-6 and MCP-1), p-JAK2 and p-STAT3 in renal cortex were significantly down-regulated. CONCLUSION: The nephroprotective effect of DJC is based on its antioxidant effect and anti-inflammatory effect via suppression of JAK2/STAT3 signal transduction.
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Objective To investigate the effects of Danzhi Jiangtang Capsule on CXCL9 and IL-8 in type 2 diabetic model rats, and discuss the mechanism in TCM intervention in type 2 diabetes. Methods Fifty male SD rats were randomly divided into 5 groups:normal control group, high-dosage group of Danzhi Jiangtang Capsule, low-dosage group of Danzhi Jiangtang Capsule, pioglitazone group and model group. Normal control group was fed with basal diet, while the other groups were fed with high fat diet. A single intraperitoneal injection of STZ of 35 mg/kg was employed to establish the animal model of diabetes mellitus. When the diabetic rodent model was built, high-dosage group of Danzhi Jiangtang Capsule and low-dosage group of Danzhi Jiangtang Capsule were treated with 1.08 g/(kg?d) and 0.54 g/(kg?d) by gavage, pioglitazone group was treated with 10 mg/(kg?d) by gavage, the blank group and the model group were treated with physiological saline 5 mL/(kg?d) by gavage for 8 weeks. CXCL9, IL-8 and blood glucose, and lipid in serum of rats were determined with double antibody sandwich method. Results Expressions of CXCL9 and IL-8 in model group increased significantly, compared with the normal control group (P<0.05, P<0.01). Expressions of CXCL9 and IL-8 in high and low dosage Danzhi Jiangtang Capsule group significantly decreased, the blood glucose and lipid also decreased, compared with model group (P<0.01). Conclusion Danzhi Jiangtang Capsule has inhibitory effects on the high expression of inflammatory factors in diabetes, and can also lower bloodglucose, and regulate blood lipid.
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This study was aimed to observe the curative effect and safety of Danzhi Jiangtang Capsule ( DJC ) combined with atorvastatin on carotid artery intima-media thickness (IMT) in diabetes patients without hyper-tension . A total of 196 diabetes patients without hypertension with incrassate carotid artery IMT were randomly divided into the control group ( 98 cases ) and the treatment group ( 98 cases ) . The conventional diabetes thera-py was given to both groups . The atorvastatin of 20 mg/night was given to the control group . And the atorvas-tatin 20 mg/night added with DJC 9 . 0 g/night were given to the treatment group . The treatment course was 12 months . Carotid artery IMT , carotid atherosclerotic plaque area , FPG , FIns , HOMA-IR , HbA1c , blood lipids , hepatorenal function and etc . were examined before and after the treatment respectively . The results showed that there was a significant positive correlation between carotid artery IMT and FIns , HOMA-IR , HbAlc , LDL-C . After 12-month treatment , the total effectiveness is 85 . 87% in the treatment group . And there was significant difference compared with the control group ( P < 0 . 05 ) . The levels of FPG , FIns , HOMA-IR , HbAlc of the treatment group had no difference compared with the control group . Compared with the control group, TC and LDL-C of the treatment group was obviously decreased (P < 0.05). And HDL-C was significantly increased ( P < 0 . 05 ) . The carotid artery IMT of the treatment group decreased from ( 0 . 11 ±0 . 01 ) cm to ( 0 . 08 ± 0 . 01 ) cm . And compared with the control group , there was statistical significance ( P <0 . 05 ) . The carotid atherosclerotic plaque area of 58 cases in the treatment group decreased from ( 0 . 37 ±0.56) cm2 to (0.21 ± 0.25) cm2. However, there was no statistical significance compared to the control group. There were 5 adverse events in the control group and 9 adverse events in the treatment group . And there was no difference between two groups. It was concluded that DJC combined with atorvastatin can regulate lipid metabolism and reduce carotid artery IMT .
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This study was aimed to observe the effect of Danzhi Jiangtang Capsule ( DJC ) on NF-κB in the peripheral blood mononuclear cell , and inflammation indices such as serum MCP-1 , TGF-β1 and urinary albu-min excretion rate ( UAER ) in early diabetic nephropathy ( EDN ) , in order to discuss the possible mechanism of DJC on anti-inflammatory and renal protection effect of EDN. A total of 72 EDN patients which met the in-clusion criteria after the start-up stage were taken as research objects . They were randomly divided into the control group and the treatment group. The western comprehensive treatment plan was given to both groups. In the treatment group, DJC was added. And the treatment course was 8 weeks. Changes of MCP-1, NF-κB, TGF-β1 and UAER were observed before and after the treatment . The results showed that MCP-1 , NF-κB and TGF-β1 had significant positive correlation with UAER ( P ment , the levels of MCP-1 , NF-κB , TGF-β1 and UAER in the control group and treatment group after treat-ment were significantly declined ( P < 0 . 05 ) . Compared with the control group , after treatment , the levels of MCP-1 , NF-κB , TGF-β1 and UAER of the treatment group were obviously reduced ( P < 0 . 05 , or P <0 . 01 ) . It was concluded that DJC can reduce the UAER , delay the renal injury , and downregulate levels of MCP-1, NF-κB and TGF-β1, block the expression of inflammatory mediators, inhibit inflammatory reaction and improve microinflammatory state of EDN. This may be one of the important mechanisms in the protection of renal function .
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This study was aimed to observe the effect of Danzhi Jiangtang Capsule ( DJC ) on expression of solu-ble thrombomodulin ( sTM ) and soluble endothelial cell protein C receptor ( sEPCR ) in experimental rats of type 2 diabetes mellitus (T2DM). This study also explored possible mechanisms of Yiqi Yangyin Huoxue method on vascular endothelial tissue and discussed mechanisms of prevention and management of T2DM vascular lesions . A total of 60 male Sprague-Dawley ( SD ) rats were fed for one week and then randomly divided into the nor-mal control group ( group N , n = 12 , rats were fed with routine food ) and diabetes mellitus group ( n = 48 , rats were fed with high-fat diet). After 4 weeks, rats in the diabetes mellitus group were injected with strepto-zotocin ( STZ ) to induce T2DM . According to the blood glucose level , rats were divided into three groups , wh ich were the model group (group M), pioglitazone (group P), and pioglitazone combined with DJC (group D). Group P was treated with pioglitazone (10 mg?kg-1?d-1), group D was given pioglitazone (10 mg?kg-1?d-1) and DJC ( 0 . 47 g?kg-1?d-1 ) . The group N and group M were treated with sodium chloride ( 5 mL?kg -1?d-1 ) . After four-week drug administration , the levels of sTM , sEPCR , PT , APTT and FIB in each group were tested . The results showed that compared with the control group , the levels of sTM , sEPCR and FIB in group M , group P and group D were significantly increased ( P < 0 . 05 ) , and the levels of PT and APTT were obviously reduced ( P < 0 . 05 ) . Compared with group P , the levels of sTM , sEPCR , FIB of group D were significantly reduced ( P< 0 . 01 ) , and the level of APTT was significantly increased ( P < 0 . 05 ) . However , there was no significant dif-ference in the increasing of PT. It was concluded that the Yiqi Yangyin Huoxue method can reduce the levels of sTM and sEPCR , and effectively improve coagulation . The possible mechanisms of protective effect on the vascular endothelium can be from reducing levels of sTM and sEPCR in order to enhance the activity of anti-coagulation and fibrinolysis , regulate the function of blood coagulation to improve hypercoagulable state .