2.Effects of puerarin on rats with type 2 diabetes mellitus.
Fei YANG ; Xin-Xin DONG ; Yun GUO
Chinese Journal of Applied Physiology 2019;35(4):355-358
OBJECTIVE:
To investigate the therapeutic effects of puerarin on rats with type 2 diabetes mellitus (T2DM).
METHODS:
T2DM models were established by high fat and high glucose feeding combined with a one-time intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Then the rats were randomly divided into normal group, model group, metformin group (MET, 40 mg/kg), puerarin low-dose group, medium-dose group and high-dose group (40, 80, 160 mg/kg), n=10. After the model was successfully established, rats were treated with corresponding drug intervention by intragastrical administration for 4 weeks. The body weight and fasting blood glucose (FBG) were measured per week, and blood samples were collected 24 h after the last administration, and serum levels of blood glucose, serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholestrol (HDL-C), serum enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine (SCr), and blood uric acid (UA) were measured.
RESULTS:
As compared with normal group, the body weight was decreased after 4 weeks-intervention in the model group, and the levels of FBG, TC, TG, LDL-C, ALT, AST, BUN, SCr and UA were all increased,while HDL-C level was decreased (P<0.05). As compared with model group,the body weight was increased after 4 weeks-intervention in metformin group and puerarin groups, and the levels of FBG, TC, TG, LDL-C, ALT, AST, BUN, SCr and UA were decreased (P<0.01); meanwhile, HDL-C level was increased significantly (P<0.05).
CONCLUSION
Puerarin can reduce the weight loss of T2DM rats, decrease the blood lipid and blood glucose levels of T2DM rats, which can be used to control T2DM.
Animals
;
Blood Glucose
;
Diabetes Mellitus, Experimental
;
drug therapy
;
Diabetes Mellitus, Type 2
;
drug therapy
;
Isoflavones
;
pharmacology
;
Lipids
;
blood
;
Random Allocation
;
Rats
;
Streptozocin
;
Weight Loss
4.Jujuboside A ameliorates tubulointerstitial fibrosis in diabetic mice through down-regulating the YY1/TGF-β1 signaling pathway.
Yang-Yang LIU ; Lin LI ; Bei JI ; Shi-Long HAO ; Xiao-Feng KUANG ; Xin-Yun CAO ; Jia-Yu YUAN ; Zhen-Zhou JIANG ; Si-Tong QIAN ; Chu-Jing WEI ; Jing XU ; Xiao-Xing YIN ; Qian LU ; Ting-Ting YANG
Chinese Journal of Natural Medicines (English Ed.) 2022;20(9):656-668
Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus, which is characterized in renal tubulointerstitial fibrosis (TIF). The current study was designed to investigate the protective effect of Jujuboside A (Ju A) on TIF in type 2 diabetes (T2DM) mice, and explore its underlying anti-fibrosis mechanism. A mouse T2DM model was established using high fat diet (HFD) feeding combined with intraperitoneal injection of streptozotocin (STZ). Then, diabetic mice were treated with Ju A (10, 20 and 40 mg·kg-1·d-1, i.g.) for 12 weeks. Results showed that administration of Ju A not only down-regulated fasting blood glucose (FBG) levels, but also improved hyperlipidemia and renal function in diabetic mice. Moreover, the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice, while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs). Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1 (YY1) in the renal cortex of diabetic mice, and reduced the levels of transforming growth factor-β1 (TGF-β1) in the serum and renal cortex of Ju A treated mice. According to invitro studies, the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose (HG) cultured HK-2 cells. Taken together, these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway.
Animals
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Blood Glucose
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Diabetes Mellitus, Experimental/metabolism*
;
Diabetes Mellitus, Type 2/drug therapy*
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Diabetic Nephropathies/metabolism*
;
Fibrosis
;
Mice
;
Saponins
;
Signal Transduction
;
Streptozocin
;
Transforming Growth Factor beta1/metabolism*
5.Effect of early intervention with rhein on islet function in db/db mice.
Hong DU ; Jia-qing SHAO ; Ping GU ; Jian WANG ; Zhi-hong LIU
Journal of Southern Medical University 2011;31(9):1526-1529
OBJECTIVETo investigate the hypoglycemic action of rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), one of the anthraquinone derivatives isolated from rhubarb, and study its effects on pancreatic beta-cells in db/db mice.
METHODSThirty 4-week-old db/db mice were randomized for an 8-week treatment with intragastric administration of rhein (120 mg/kg, n=15) or placebo (1% natrium cellulose solution, n=15). After the treatment, intraperitoneal glucose tolerance test (IPGTT) was performed and the area under curve (AUC) of insulin levels in IPGTT was calculated to evaluate insulin secretory function. The AUC(INS0-30) was calculated to evaluate the early-phase insulin secretion. Immunohistochemical staining for insulin was performed to estimate the beta-cell mass, and beta-cell apoptosis was detected using TUNEL assay.
RESULTSCompared with the control group, rhein-treated group showed significantly reduced blood glucose concentrations at 0, 30, 60 and 120 min after glucose load with significantly higher insulin levels at 30, 60 and 120 min. The early-phase insulin secretion was also obviously increased. The beta-cell mass was obviously rescued by the 8-week treatment with rhein, which also notably improved the staining intensity of insulin and suppressed beta-cell apoptosis compared with the control.
CONCLUSIONSEarly rhein treatment significantly improves glucose tolerance by restoring the early-phase insulin secretion in db/db mice and inhibiting the apoptosis of the beta-cells, suggesting the potential of rhein as a novel therapeutic agent for type 2 diabetes.
Animals ; Anthraquinones ; pharmacology ; Apoptosis ; drug effects ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Disease Models, Animal ; Hypoglycemic Agents ; pharmacology ; Insulin ; secretion ; Insulin-Secreting Cells ; drug effects ; Male ; Mice
6.Mechanisms of the role of fibroblast growth factor 21 in attenuating insulin resistance.
Tong-yu XU ; Wen-fei WANG ; Peng-fei XU ; Qing-yan YUAN ; Shuang-qing LIU ; Tong ZHNAG ; Gui-ping REN ; De-shan LI
Acta Pharmaceutica Sinica 2015;50(9):1101-1106
This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on type 2 diabetic mice model and to provide mechanistic insights into its therapeutic effect. Type 2 diabetic animal model was established with high calorie fat diet and low dose streptozotocin (STZ) injection. Mice were then randomized into 5 groups: model control, FGF21 0.25 and 0.05 μmol x kg(-1) x d(-1) groups, insulin treatment group. Ten age-matched normal KM mouse administered with saline were used as normal controls. Serum glucose, insulin, lipid products and the change of serum and liver tissue inflammation factor levels between five groups of mouse were determined. The results showed that blood glucose, insulin, free fatty acids (FFAs), triglycerides, and inflammatory factor average FGF-21 of type 2 diabetes model group and normal control group were significantly higher (P < 0.01), while compared with insulin group, no difference was significant. Average blood glucose, insulin, blood lipid and inflammatory factor of FGF-21 treatment group compared with type 2 diabetes group was significantly lower (P < 0.01) and insulin group has no difference with the model control group. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF-21 significantly remits type 2 diabetic mice model's insulin resistance state and participates in the regulation of inflammatory factor levels and type 2 diabetes metabolic disorders.
Animals
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Blood Glucose
;
Diabetes Mellitus, Experimental
;
drug therapy
;
Diabetes Mellitus, Type 2
;
drug therapy
;
Diet, High-Fat
;
Fatty Acids, Nonesterified
;
blood
;
Fibroblast Growth Factors
;
pharmacology
;
Insulin
;
blood
;
Insulin Resistance
;
Mice
;
Streptozocin
;
Triglycerides
;
blood
7.Effects of alpha-linolenic acid on inflammation and oxidative stress in the diabetic rats.
Li-Hua ZHANG ; Wei ZHANG ; Guang-Hong WEI ; Pei YANG ; Jun LIU ; Xiao-Lin NIU
Chinese Journal of Applied Physiology 2012;28(1):64-67
OBJECTIVETo investigate the effects of alpha-linolenic acid (ALA) on inflammation and oxidative stress in the diabetic rats.
METHODSAn experimental type 2 diabetes mellitus model was induced by feeding male SD rats with diet of high fat for 4 weeks and then injected them intraperitoneally with streptozocin (STZ) at 30 mg/kg. Then the animals were randomly divided into three groups (n = 10): control group, diabetic group and ALA group. Four weeks later, tumor necrosis factor (TNF)-a, soluble P-selectin (sP-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), nitric oxide (NO) production, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in the serum were determined.
RESULTSInflammatory agents including TNF-alpha, sP-selectin and sICAM-1 increased in diabetic rats to compare with control group. Treatment with ALA significantly decreased TNF-alpha, sP-selectin and slCAM-1 to compare with diabetic group. Furthermore, compared with control group, serum MDA production increased whereas NO production, SOD and CAT activities decreased in diabetic rats. Treatment with ALA reduced MDA production, increased NO production, promoted SOD and CAT activities compared with diabetic group.
CONCLUSIONThese results indicate that diet rich in ALA exerted the anti-inflammatory and anti-oxidative effects in diabetic rats, which may be beneficial to the prevention and treatment of diabetes.
Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Inflammation ; Male ; Malondialdehyde ; blood ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood ; Tumor Necrosis Factor-alpha ; blood ; alpha-Linolenic Acid ; pharmacology ; therapeutic use
8.Effects of different compatibility proportion of jiaotai pills on treating type 2 diabetes mellitus in rats.
Jianhong WANG ; Fuer LU ; Hui DONG ; Yanlin GONG ; Lijun XU ; Xin ZOU ; Guang CHEN
China Journal of Chinese Materia Medica 2011;36(16):2271-2276
OBJECTIVETo study the effects of different compatibility proportion of Jiaotai pills on treating type 2 diabetes mellitus (T2DM) in rats.
METHODThe model of type 2 diabetes mellitus in rats was established by injecting streptozotocin from tail vein and feeding with high fat and high caloric diet. Diabetic rats were randomly divided into model group, Jiaotai pill 1 group (Coptidis Rhizoma-cinnamon 2: 1), Jiaotai pill 2 group (Coptidis Rhizoma-cinnamon 4: 1), Jiaotai pill 3 group (Coptidis Rhizoma-cinnamon 10: 1) and metformin group. Rats in different treatment groups were given by corresponding therapy from gastric tube. Meanwhile normal control group was another set. Body weight, oral glucose tolerance test (OGTT), blood lipid level including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), plasma levels of free fatty acid (FFA) and adiponectin, plasma liver enzymes activity(ALT, AST, AKP, gamma-GT) and pathological results of liver tissue were determined after eight weeks.
RESULTBody weight, fasting plasma glucose (FPG), postpradial plasma glucose at one hour (PG-1 h), postpradial blood glucose at two hour (PG-2 h), plasma levels of TC, TG, LDL-C, FFA and liver enzymes activity were all increased in rats of model group compared with those in normal control group. Plasma levels of HDL-C and adiponectin were decreased in model group (P < 0.01). Fatty degeneration of hepatocytes was apparent in liver tissues in rats of model group. Compared with model group results of OGTT, blood lipid levels and liver enzymes activity were improved while levels of HDL-C and adiponectin were increased in rats of different treatment groups (P < 0.05 or P < 0.01). Meanwhile fatty degeneration of hepatocytes was improved in liver tissues in rats of different treatment groups. Compared with metformin group, plasma level of HDL-C was elevated while AKP and gamma-GT were decreased significantly in rats of Jiaotai pill 1 group (P < 0.05), gamma-GT level was decreased significantly in rats of Jiaotai pill 2 group (P < 0.05), AST, AKP and gamma-GT levels were decreased significantly in rats of Jiaotai pill 3 group (P < 0.05). Compared with Jiaotai Pill 1 group, plasma levels of HDL-C was decreased while AKP levels was elevated significantly in rats of Jiaotai pill 2 group, but HDL-C was decreased in rats of Jiaotai pill 3 group (P < 0.05).
CONCLUSIONIt is suggested that different compatibility proportion of Jiaotai pills are effective on treating type 2 diabetes mellitus in rats. The effect of Jiaotai pill 1 group is better than that of other therapy groups.
Animals ; Blood Glucose ; analysis ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Fatty Acids, Nonesterified ; blood ; Lipids ; blood ; Male ; Medicine, Chinese Traditional ; Rats ; Streptozocin
9.Influence of Zea mays L. saponin (ZMLS) on ultrastructure of kidney and pancreas in diabetes rats induced by streptozocin.
Ming-San MIAO ; Gui-Lan ZHANG ; Yan-Yan MIAO ; Jing-Jing SHI ; Hui-Li LIU
China Journal of Chinese Materia Medica 2008;33(10):1179-1183
OBJECTIVETo discuss the effect of Zea mays L. saponin (ZMLS) on ultrastructure of kidney and pancreas in the diabetes rats induced by streptozocin.
METHODThe diabetic rat model was established by injections of STZ, blood glucose, the ultrastructure of the kidney and pancreas were observed.
RESULTCompared with the model group, the large, middle-dose ZMLS groups and melbinum group could remarkably decrease the blood glucose (P < 0.01), the large, middle, small-dose ZMLS groups could remarkably prevent the pancreatic islet beta-cell from the injury induced by Streptozotocin. Melbinum and the large, middle-dose ZMLS groups could remarkably increase mitochondrial Vv, deltam and euchromatin Vv (P < 0.01), and significantly decrease the delta, Nucleus delta and heterochromatin Vv (P < 0.01). The small dose of ZMLS obviously increases mitochondrial Vv (P < 0.05).
CONCLUSIONZMLS showed good effect on decreasing blood glucose and protection action on the kidney and pancreas injury of induced by STZ.
Animals ; Blood Glucose ; drug effects ; Diabetes Mellitus ; drug therapy ; Diabetes Mellitus, Experimental ; drug therapy ; Humans ; Kidney ; drug effects ; ultrastructure ; Male ; Pancreas ; drug effects ; ultrastructure ; Plant Extracts ; administration & dosage ; Rats ; Rats, Wistar ; Saponins ; administration & dosage ; Streptozocin ; Zea mays ; chemistry
10.Effects of Yuquan pills on pharmacokinetics of metformin hydrochloride in diabetic rats.
Hao-Gang DUAN ; Yu-Hui WEI ; Bo-Xia LI ; Dong-Mei ZHANG ; Jin-Wen ZHANG ; Xin-An WU
China Journal of Chinese Materia Medica 2008;33(18):2133-2139
OBJECTIVETo study effects of Yuquan pills on the pharmacokinetics process of metformin hydrochloride in diabetic rats.
METHODAfter administration Yuquan pills 7 day to the diabetic rats, the metformin hydrochloride was orally administrated, then the blood samples were collected at different time. The concentrations of metformin hydrochloride in plasma were determined by HPLC method and the pharmacokinetic parameters were calculated.
RESULTThe pharmacokinetic parameter Cmax of the controlling group and the testing group were respectively, 18.95, 21.76 mg x L(-1); t1/2 were 1,069.8, 1,767.4 min, respectively; CL/F were 0.013, 0.008 L x min(-1) x kg(-1); AUC were 10,042.1, 10,712.2 mg z L(-1) x min(-1) respectively.
CONCLUSIONThe pharmacokinetics process of metformin hydrochloride in diabetic rats fits one-compartment model. Yuquan pills has a significant effect on the pharmacokinetics of metformin hydrochloride in diabetic rats.
Animals ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; metabolism ; Drug Interactions ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Metformin ; blood ; pharmacokinetics ; Rats ; Rats, Wistar