Tunhai Xu

Antihyperglycemic and antihyperlipidemic action of cinnamaldehyde in C57BLKS/J db/db mice.

OBJECTIVEnTo investigate the effects of cinnamaldehyde (CA), an active and major compound in cinnamon, on glucose metabolism and insulin resistance in C57BLKS/J db/db mice.nnnMETHODSnSixteen male C57BLKS db/db mice were randomly divided into control and CA treatment groups. CA was given (20 mg x kg(-1) x day(-1), p. o.) for 4 weeks. Pure water was given to control and db/+ mice. Subsequently, the levels of fasting blood glucose (FBG), fasting serum insulin, triglyeride, cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and free fatty acids (FFA), as well as the mRNA content of adiponectin and tumor necrosis factor (TNF)-alpha in adipose tissue, glucose transporter type 4 (GLUT-4) in skeletal muscle, and protein expressions of Akt, phospho-Akt (Thr308), AMPKalpha, phospho-AMPKalpha (Thr172) in skeletal muscle were measured.nnnRESULTSn1) CA decreased serum levels of FBG and insulin as well as body weight in db/db mice; 2) CA increased serum HDL-C levels; 3) CA significantly decreased the mRNA expression of TNF-alpha in adipose tissue and upregulated mRNA expression of GLUT-4 in skeletal muscle; 4) protein expression of p-Akt was increased in CA-treated mice, but Akt, AMPKalpha and p-AMPKalpha showed no change.nnnCONCLUSIONnCA has antihyperglycemic and antihyperlipidemic actions in db/db mice and could be useful in the treatment of type-2 diabetes.

Effect of mulberry leaf (Folium Mori) on insulin resistance via IRS-1/PI3K/Glut-4 signalling pathway in type 2 diabetes mellitus rats

Abstract Context: Folium Mori, the leaf of Morus alba L. (Moraceae), has been used in traditional Chinese medicine (TCM) for treating diabetes. However, it is unclear which components in the mulberry leaf are effective for the treatment of type 2 diabetes mellitus (T2DM). Objective: To investigate the flavonoids and polyphenols in mulberry leaves and their antihyperglycemic and antihyperlipidemic effects in T2DM rats. Materials and methods: Male Sprague-Dawley rats were divided into five groups: normal control (NC), diabetic control (DBC), diabetic group with 0.3u2009mg/kg b.w./day rosiglitazone (RSG), diabetic group with 7u2009g/kg b.w./day TCM formula and diabetic group with 2u2009g/kg b.w./day Folium Mori extract (FME). After 4 weeks, the rats were sacrificed; biochemical parameters, gene and protein expression were measured. Results: The FBG level was significantly lower in the FME group than in the DBC group (pu2009<u20090.05). In oral glucose tolerance test, the AUC was significantly lower in the FME group (pu2009<u20090.05). The HOMA-IR level was significantly decreased in the FME group (pu2009<u20090.05). FME decreased the total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) levels (pu2009<u20090.05). FME increased the mRNA and protein expression of IRS-1, PI3K p85α and Glut-4 increased significantly (pu2009<u20090.05). Histological analysis revealed amelioration of lipid accumulation following FME treatment. Additionally, immunohistochemical analysis displayed stronger staining of Glut-4 in the FME group compared to the DBC group. Discussion and conclusion: FME could decrease the body weight, blood glucose, TG, TC and LDL levels, and improve insulin resistance. FME possessed significant antihyperglycemic and antihyperlipidemic activities via the IRS-1/PI3K/Glut-4 signalling pathway.

Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle

BackgroundMetabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome.MethodsMale rats at 7xa0weeks of age were administered with vehicle water or treated by gavage with 2xa0g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured.ResultsCompared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120xa0min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42xa0days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles.ConclusionsThese data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.

Tanshinone I alleviates insulin resistance in type 2 diabetes mellitus rats through IRS-1 pathway

Tanshinone I from tanshen has been used in traditional Chinese medicine for treating cardiovascular diseases and inflammatory diseases. Given the link between inflammation and Type 2 diabetes mellitus (T2DM), we suspect that tanshinone I may have a beneficial effect on T2DM. This study was to investigate the potential effects of tanshinone I on T2DM and its underlying mechanism. T2DM was thus induced in Sprague-Dawley (SD) rats using streptozotocin (STZ) and high-fat diet. It was observed that T2DM rats had higher levels of total cholesterol (TC), nonesterified fatty acids (NEFAs), total triglyceride (TG) and total low density lipoprotein cholesterol (LDL-C) compared with normal, healthy SD rats. Treatment with tanshinone I decreased these levels and lowered blood glucose level in T2DM rats. In addition, enzyme-linked immunosorbent assay (ELISA) analysis showed that T2DM rats had elevated levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Furthermore, Western blot analysis revealed that T2DM rats had enhanced nuclear translocation of NF-κB as well as elevated phosphorylation of Ser307 in IRS-1(insulin receptor substrate 1). Treatment by tanshinone I lowered the levels of IL-6 and TNF-α, decreased nuclear translocation of NF-κB as well as phosphorylation of Ser307 in IRS-1. These results demonstrated that tanshinone I could alleviate T2DM syndrome in rats.

Protective effects of asiatic acid in a spontaneous type 2 diabetic mouse model

Asiatic acid (AA) has been demonstrated to exhibit anti-diabetic activity. However, the mechanisms and underlying signaling pathways remain to be elucidated. The present study was performed to confirm the protective effect of AA and demonstrate its ability to regulate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) signaling pathway in db/db mice. Db/db mice fed on a high-fat diet were used to model diabetes mellitus. Modeled mice were divided randomly into the model control, pioglitazone hydrochloride tablet (PH) and AA groups. Age-matched C57 BL/6J mice served as normal controls. Lipid and glucose levels, and glycogen synthesis rates were assessed following treatment. Pathological changes were detected using hematoxylin and eosin staining. Expression of the PI3K/AKT/GSK-3β signaling pathway at the mRNA level was measured using quantitative polymerase chain reaction analysis. The model control group revealed typical characteristics of obesity and diabetes, including high glucose and lipid levels, and decreased glycogen synthesis. Four weeks of treatment with AA or PH ameliorated these abnormalities. AA and PH treatments mitigated the upregulation of PI3K, AKT, insulin receptor, and insulin receptor substrate-1 mRNA expression in modeled mice. Furthermore, AA and PH treatments decreased GSK-3β and glucose-6-phosphatase mRNA expression compared with the normal control group. The results of the present study confirmed that AA possesses anti-diabetic activity in db/db mice. The PI3K/AKT/GSK-3β signaling pathway may mediate this protective effect.

Curcumin suppresses AGEs induced apoptosis in tubular epithelial cells via protective autophagy

Renal tubular cell apoptosis and tubular dysfunction is an important process underlying diabetic nephropathy (DN). Understanding the mechanisms underlying renal tubular epithelial cell survival is important for the prevention of kidney damage associated with glucotoxicity. Curcumin has been demonstrated to possess potent anti-apoptotic properties. However, the roles of curcumin in renal epithelial cells are yet to be defined. The present study investigated advanced glycation or glycoxidation end-product (AGE)-induced toxicity in renal tubular epithelial cells via several complementary assays, including cell viability, cell apoptosis and cell autophagy in the NRK-52E rat kidney tubular epithelial cell line. The extent of apoptosis was significantly increased in the NRK-52E cells following treatment with AGEs. The results also indicated that curcumin reversed this effect by promoting autophagy through the phosphoinositide 3-kinase/AKT serine/threonine kinase signaling pathway. These conclusions suggested that curcumin exerts a renoprotective effect in the presence of AGEs, at least in part by activating autophagy in NRK-52E cells. Collectively, these findings indicate that curcumin not only exerts renoprotective effects, however may also act as a novel therapeutic strategy for the treatment of diabetic nephropathy.

Tang-Nai-Kang Alleviates Pre-diabetes and Metabolic Disorders and Induces a Gene Expression Switch toward Fatty Acid Oxidation in SHR.Cg-Leprcp/NDmcr Rats

Increased energy intake and reduced physical activity can lead to obesity, diabetes and metabolic syndrome. Transcriptional modulation of metabolic networks has become a focus of current drug discovery research into the prevention and treatment of metabolic disorders associated with energy surplus and obesity. Tang-Nai-Kang (TNK), a mixture of five herbal plant extracts, has been shown to improve abnormal glucose metabolism in patients with pre-diabetes. Here, we report the metabolic phenotype of SHR.Cg-Lepr cp/NDmcr (SHR/cp) rats treated with TNK. Pre-diabetic SHR/cp rats were randomly divided into control, TNK low-dose (1.67 g/kg) and TNK high-dose (3.24 g/kg) groups. After high-dose treatment for 2 weeks, the serum triglycerides and free fatty acids in SHR/cp rats were markedly reduced compared to controls. After 3 weeks of administration, the high dose of TNK significantly reduced the body weight and fat mass of SHR/cp rats without affecting food consumption. Serum fasting glucose and insulin levels in the TNK-treated groups decreased after 6 weeks of treatment. Furthermore, TNK-treated rats exhibited obvious improvements in glucose intolerance and insulin resistance. The improved glucose metabolism may be caused by the substantial reduction in serum lipids and body weight observed in SHR/cp rats starting at 3 weeks of TNK treatment. The mRNA expression of NAD+-dependent deacetylase sirtuin 1 (SIRT1) and genes related to fatty acid oxidation was markedly up-regulated in the muscle, liver and adipose tissue after TNK treatment. Furthermore, TNK promoted the deacetylation of two well-established SIRT1 targets, PPARγ coactivator 1α (PGC1α) and forkhead transcription factor 1 (FOXO1), and induced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in different tissues. These observations suggested that TNK may be an alternative treatment for pre-diabetes and metabolic syndrome by inducing a gene expression switch toward fat oxidation through the activation of SIRT1 and AMPK signaling.

Synthesis and Biological Activity of Isoflavone Derivatives from Chickpea as Potent Anti-Diabetic Agents

A set of novel isoflavone derivatives from chickpea were synthesized. The structures of derivatives were identified by proton nuclear magnetic resonance (1H-NMR), carbon-13 (13C)-NMR and mass spectrometry (MS) spectral analyses. Their anti-diabetic activities were evaluated using an insulin-resistant (IR) HepG2 cell model. Additionally, the structure-activity relationships of these derivatives were briefly discussed. Compounds 1c, 2h, 3b, and 5 and genistein exhibited significant glucose consumption-enhancing effects in IR-HepG2 cells. In addition, the combinations of genistein, 2h, and 3b (combination 6) and of 3b, genistein, and 1c (combination 10) exhibited better anti-diabetic activity than the individual compounds. At the same dosage, there was no difference in effect between the combination 10 and the positive control (p > 0.05). Aditionally, we found the differences between the combination 10 and combination 6 for the protective effect of HUVEC (human umbilical vein endothelial cells) under high glucose concentration. The protective effects of combination 10 was stronger than combination 6, which suggested that combination 10 may have a better hypoglycemic activity in future studies. This study provides useful clues for the further design and discovery of anti-diabetic agents.

Qiwei granules alleviates podocyte lesion in kidney of diabetic KK-Ay mice

BackgroundChinese medicine comprised of all natural herbs is widespread used in the treatment of diabetic nephropathy (DN). Podocyte contributes to the integrity of glomerular filtration barrier whose injury plays an important role in the initiation and progression of DN. Our study aimed to investigate the effect of Qiwei granules on podocyte lesion in diabetic KK-Ay mice kidney and its underlying mechanism.MethodsTwelve-week-old male KK-Ay mice were randomly divided in vehicle group and Qiwei granules group, while C57BL/6J mice were used as normal control. The mice were gavage with 1.37xa0g/kg/day Qiwei granules or water for 10xa0weeks. We measured water, food intake and body weight (BW) and fasting blood glucose (FBG) every 2xa0weeks, and urine protein every 4xa0weeks. At the end of the experiment, all surviving mice were sacrificed. The kidney weight and serum renal parameters were measured, and the renal morphology was observed. To search the underlying mechanism, we examined the podocyte positive marker, slit diaphragm protein expression and some involved cell signal pathway.ResultsQiwei granules treatment significantly improved the metabolic parameters, alleviated the urinary protein, and protected renal function in KK-Ay mice. In addition, the glomerular injuries and podocyte lesions were mitigated with Qiwei granules treatment. Furthermore, Qiwei granules increased expression of nephrin, CD2AP, and integrin alpha3beta1 in the podocytes of KK-Ay mice. Qiwei granules improved the phosphoration of Akt and inhibited cleaved caspase-3 protein expression.ConclusionThese finding suggest that Qiwei granules protects the podocyte from the development of DN via improving slit diaphragm (SD) molecules expression and likely activating Akt signaling pathway in KK-Ay mice.

Cyclocarya paliurus (Batal.) Ijinskaja Aqueous Extract (CPAE) Ameliorates Obesity by Improving Insulin Signaling in the Hypothalamus of a Metabolic Syndrome Rat Model.

Background Antiobesity drugs may not be optimal for treating obesity. However novel antiobesity agents, especially those derived from natural products, may be suitable. Therefore, we investigated the effects and mechanisms of Cyclocarya paliurus (CP) aqueous extract (CPAE) on obesity. Methods SHR.Cg-Leprcp/NDmcr (SHR/cp) rats were used as a model of obesity and metabolic syndrome. Experimental animals were allocated into two groups—control and CPAE (0.5u2009g/kg)—for a 7-week treatment period. Examinations were performed, including general physiological characteristics, obesity-related biochemical parameters, and insulin-signaling pathway-related proteins in the hypothalamus. Results Treatment with CPAE reduced food intake, body weight, organ weight, fat mass, and body mass index (BMI) in SHR/cp rats. Meanwhile, CPAE also decreased the levels of fasting serum glucose, fasting serum insulin, HOMA-IR, serum free fatty acids, serum malondialdehyde, serum superoxide dismutase, and serum total-glutathione. The levels of phosphorylation of target proteins—including InsR, IRS1, PI3Kp85, Akt, and FoXO1 as well as protein expression of POMC—were significantly upregulated in the hypothalamus, but NPY expression remarkably decreased. Conclusions CPAE has antiobesity, antihypoglycemic, antihypolipidemic, and antioxidant properties. The mechanism responsible for the antiobesity effect of CPAE may be related to suppression of energy intake via regulation of insulin-signaling pathway in the hypothalamus.