Xiaoqian Dai

Epigallocatechin-3-O-gallate (EGCG) protects the insulin sensitivity in rat L6 muscle cells exposed to dexamethasone condition.

The tea polyphenol epigallocatechin-3-O-gallate (EGCG) displays some antidiabetic effects; however the mechanisms are incompletely understood. In the present study, the investigation of the effects of EGCG on insulin resistance was performed in rat L6 cells treated with dexamethasone. We found that dexamethasone increased Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1) and reduced phosphorylation of AMPK and Akt. Furthermore, glucose uptake and glucose transporter (GLUT4) translocation were inhibited by dexamethasone. However, the treatment of EGCG improved insulin-stimulated glucose uptake by increasing GLUT4 translocation to plasma membrane. Furthermore, we also demonstrated these EGCG effects essentially depended on the AMPK and Akt activation. Together, our data suggested that EGCG inhibited dexamethasone-induced insulin resistance through AMPK and PI3K/Akt pathway.

Grape seed proanthocyanidin extracts alleviate oxidative stress and ER stress in skeletal muscle of low‐dose streptozotocin‐ and high‐carbohydrate/high‐fat diet‐induced diabetic rats

Although ER stress in pancreas, liver, and adipose tissue was reported to be a novel event linked to the pathogenesis of type 2 diabetes mellitus, there is much less information on this event in skeletal muscle. Some studies indicated that treatment with antioxidants had beneficial effects on ER stress and diabetes. This study focuses on the effects of a strong antioxidant, grape seed proanthocyanidin extracts (GSPE), on skeletal muscle in diabetic rats induced with low dose streptozotocin- and a high-carbohydrate/high-fat diet. After 16 wk of GSPE treatment, diabetic rats showed decreased plasma glucose levels and insulin resistance. The efficacious effect of GSPE was manifested by the amelioration of muscular damage and dysfunction, as observed by histological examination and periodic acid Schiff staining. Concurrently, calcium overload and the abnormal activities of antioxidant enzymes and ATPases in diabetic muscles were partially reversed by GSPE treatment. GSPE also increased the activity of protein kinase B (a mediator of insulins metabolic action) and partially alleviated severe ER stress. These findings suggest that GSPE may have auxiliary therapeutic potential for type 2 diabetes mellitus by decreasing oxidative stress and ER stress in skeletal muscle.

Effect of polysaccharide from cultured Cordyceps sinensis on immune function and anti-oxidation activity of mice exposed to 60Co

AIM OF THE STUDY The present study was designed to investigate the molecular weight (MW), chemical composition and effect of polysaccharide (CS-PS), from the fruiting bodies of cultured Cordyceps sinensis, on immune function and anti-oxidation activity of BALB/c mice exposed to (60)Co. MATERIALS AND METHODS The MW of CS-PS was determined by gel-filtration. The chemical composition of CS-PS was tested by using gas chromatography-mass spectrophotometer (GC-MS). Mice were administered CS-PS with doses of 50, 100 or 200mg/kg body weight, then exposed to (60)Co. The normal control group and irradiated control group were also used. Four days later, lymphocyte proliferation, activity of macrophage phagocytosis, delayed type hypersensitivity (DTH), concentration of malondialdehyde (MDA), total-superoxide dismutase (SOD) enzyme activity, and cytokine expression in serum from the mice were tested. RESULTS The average molecular weight of CP-PS was 12 kD. The polysaccharide was composed of mannose, rhamnose, arabinose, xylose, glucose and galactose. Lymphocyte proliferation, the activity of macrophage phagocytosis, DTH and total-SOD enzyme activity in the CS-PS groups were significantly enhanced compared to the irradiated control group. Lipid peroxidation level was significantly reduced in the CS-PS groups compared to the irradiated control group. Levels of cytokine IL-4, IL-5 and IL-17 are also affected in the CS-PS groups compared to the irradiated control group. CONCLUSIONS CS-PS, a heteropolysaccharide, enhances immunity activity in mice treated by ionizing radiation, through reducing oxidative injury and modulating the secretion of cytokine IL-4, IL-5 and IL-17.

Epigallocatechin-3-gallate protects pro-inflammatory cytokine induced injuries in insulin-producing cells through the mitochondrial pathway

Pro-inflammatory cytokine-mediated pancreatic β-cell dysfunction is a key pathological event in type 1 diabetes mellitus. There are few studies about the protection of epigallocatechin-3-gallate (EGCG) against pro-inflammatory cytokine-induced β-cell apoptosis. To examine the direct effects of EGCG on β-cells, insulin-producing RINm5F cells were exposed to a combination of recombinant interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), with or without EGCG pretreatment for 24h. Cell death was monitored by the MTT assay. Glucose-stimulated insulin release was measured using radio immunoassay. Intracellular reactive oxygen species was examined with dichlorofluorescein (DCF) fluorescence by flow cytometry. To evaluate RINm5F cells mitochondrial function, change in mitochondrial membrane potential, intracellular ATP levels, and nitric oxide was assessed. The expression of cytochrome c, Bax, Bcl-2, and iNOS proteins was measured by western blotting. In the present study, EGCG pretreatment protected against cytokines inducing cell death and restored glucose stimulated-insulin secretion in RINm5F cells. EGCG reduced the cytokine-induced generation of reactive oxygen species, the loss of mitochondrial membrane potential (Δψm), the release of cytochrome c from the mitochondria, and translocation of Bax protein to the mitochondria from the cytosol. EGCG pretreatment prevented cytokine-induced iNOS overexpression and NO generation. In summary, pro-inflammatory cytokines lead to a reduction of glucose-induced insulin secretion, mitochondrial activity and viability in RINm5F cells. The pro-inflammatory cytokine-induced effects can be prevented by EGCG pretreatment via the mitochondrial pathway.

Oral administration of marine collagen peptides from Chum Salmon skin enhances cutaneous wound healing and angiogenesis in rats.

BACKGROUND A wound is a clinical entity which often poses problems in clinical practice. The present study was aimed to investigate the wound healing potential of administering marine collagen peptides (MCP) from Chum Salmon skin by using two wound models (incision and excision) in rats. RESULTS Ninety-six animals were equally divided into the two wound models and then within each model animals were randomly divided into two groups: vehicle-treated group and 2 g kg(-1) MCP-treated group. Wound closure and tensile strength were calculated. Collagen deposition was assessed by Masson staining and hydroxyproline measurement. Angiogenesis was assessed by immunohistological methods. MCP-treated rats showed faster wound closure and improved tissue regeneration at the wound site, which was supported by histopathological parameters pertaining to wound healing. MCP treatment improved angiogenesis and helped form thicker and better organised collagen fibre deposition compared to vehicle-treated group. CONCLUSION The results show the efficacy of oral MCP treatment on wound healing in animals.

Myricetin Protects Against Cytokine-Induced Cell Death in RIN-m5f β Cells

Cytokine-induced cell death is recognized as a major cause of progressive β-cell loss. Tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ) in combination trigger a series of events that lead to β-cell death. In the past few decades, the use of myricetin as an anti-inflammatory and cytoprotective agent has gained much attention. The present study focused on the protective roles of myricetin against cytokine-induced cell death in insulin-secreting RIN-m5f β cells. The results showed that myricetin (especially at concentrations of 10 μM and 20 μM) increased cell viability and decreased cell apoptosis induced by the cytokine mixture of TNF-α (10 ng/mL), IL-1β (5 ng/mL), and IFN-γ (1000 IU/mL) for 3 days. Moreover, the cytokines increased the total and p65 subunit levels of nuclear factor κB, decreased inhibitor κB α levels, stimulated the accumulation of nitric oxide, increased cytochrome c release from mitochondria, and induced reactive oxygen species generation; myricetin (especially at the concentration of 20 μM) abolished all of these parameters. These results suggest that myricetin might have therapeutic value for preventing β-cell death.

Functional and morphological effects of grape seed proanthocyanidins on peripheral neuropathy in rats with type 2 diabetes mellitus.

Grape seed proanthocyanidins (GSPs) possess a broad spectrum of pharmacological and therapeutic properties. The aim of this study was to examine the effect of GSPs on functional and morphological abnormalities in the peripheral nerves of rats with type 2 diabetes mellitus. Diabetic rats were induced by two injections of 25 mg streptozotocin/kg body weight and 8 weeks of a high‐carbohydrate/high‐fat diet. GSPs were then administrated to the rats for 16 weeks. Thermal and mechanical sensitivity thresholds and nerve conductive velocity were measured to evaluate peripheral nerve function. Light microscopy was used with special stains to observe the morphological changes in the central and peripheral nervous systems. Calcium (Ca2+) homeostasis and ATPase activities in the sciatic nerves were also determined. In diabetic rats receiving GSP treatment (especially at the 500 mg/kg dose), the abnormal peripheral nerve function and impaired nervous tissues (L4 to L5 spinal cord segments, L5 dorsal root ganglion, and sciatic nerves) were improved to a significant extent. Moreover, 500 mg/kg GSP treatment significantly reduced the concentration of free Ca2+ and elevated Ca2+‐ATPase activity in sciatic nerves. These results suggest that GSPs may prevent early functional and morphological abnormalities in the peripheral nerves of rats with type 2 diabetes mellitus. Copyright

Effects of grape seed proanthocyanidin extract on renal injury in type 2 diabetic rats

Grape seed proanthocyanidin extract (GSPE) is known to be an effective natural polyphenol capable of removing free radicals in vivo. It has been reported that GSPE has biological functions including antioxidant, anti-cancer, anti-hyperglycemic, anti-radiation, and prevention and treatment of cardiovascular diseases. This study aims to investigate the effects of GSPE on renal injury in type 2 diabetic rats induced with low-dose streptozotocin and a high-carbohydrate/high-fat diet. Rats (n=12 per group) were administered GSPE at either a low (125 mg/kg · bw), medium (250 mg/kg · bw) or high (500 mg/kg · bw) dose, while control rats and diabetes mellitus group rats received no specific treatment. After 16 weeks, GSPE slightly increased body weight and decreased food consumption, water intake and urine volume in rats. Diabetic rats treated with GSPE demonstrated decreased fasting blood glucose, serum insulin, HbA1c and systolic blood pressure (P<0.05). GSPE significantly improved renal function parameters, reduced the expression of tissue inhibitor of metalloproteinase-1 and also increased the activity of matrix metalloproteinase-9. Moreover, GSPE (particularly at a dose of 500 mg/kg · bw) increased the activity of antioxidant enzymes and reduced the levels of c-reactive proteins (P<0.01) in serum and the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 (P<0.05) in the kidney. These findings suggest that GSPE ameliorates renal injury in type 2 diabetic rats through its antioxidative activity and anti-inflammatory effects.

Oral Administration of Skin Gelatin Isolated from Chum Salmon (Oncorhynchus keta) Enhances Wound Healing in Diabetic Rats

Care for diabetic wounds remains a significant clinical problem. The present study was aimed at investigating the effect of skin gelatin from Chum Salmon on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 48 rats, of which 32 were diabetes. The diabetic rats were orally treated daily for 14 days with skin gelatin from Chum Salmon (2 g/kg) or its vehicle. Sixteen non-diabetic control rats received the same amount of water as vehicle-treated non-diabetic rats. Rats were killed to assess the rate of wound closure, microvessel density (MVD), vascular endothelial growth factor (VEGF), hydroxyproline (HP) contents in wound tissues and nitrate in plasma and wound tissue at 7 and 14 days after wounding. Skin gelatin-treated diabetic rats showed a better wound closure, increased MVD, VEGF, hyproxyproline and NO contents and a reduced extent of inflammatory response. All parameters were significant (P < 0.05) in comparison to vehicle-treated diabetic group. In light of our finding that skin gelatin of Chum Salmon promotes skin wound repair in diabetic rats, we propose that oral administration of Chum Salmon skin gelatin might be a beneficial method for treating wound disorders associated with diabetes.

Proanthocyanidins protect against early diabetic peripheral neuropathy by modulating endoplasmic reticulum stress

Diabetic peripheral neuropathy (DPN) is the most common and troublesome complication of type 2 diabetes mellitus (T2DM). Recent findings reveal an important role of endoplasmic reticulum (ER) stress in the development of DPN and identify a potential new therapeutic target. Schwann cells (SC), the myelinating cells in peripheral nervous system, are highly susceptible to ER homeostasis. Grape seed proanthocyanidins (GSPs) have been reported to improve DPN of type 1 diabetic rats and relieve ER stress in skeletal muscles and pancreas of T2DM. We investigated the potential role of ER stress in SC in regulating DPN of T2DM and assessed whether early intervention of GSPs would prevent DPN by modulating ER stress. The present study was performed in Sprague-Dawley rats made T2DM with low-dose streptozotocin and a high-carbohydrate/high-fat diet and in rat SC cultured in serum from type 2 diabetic rats. Diabetic rats showed a typical characteristic of T2DM and slowing of nerve conduction velocity (NCV) in sciatic/tibial nerves. The lesions of SC, Ca(2+) overload and ER stress were present in sciatic nerves of diabetic rats, as well as in cell culture models. GSPs administration significantly decreased the low-density lipoprotein level and increased NCV in diabetic rats. GSPs or their metabolites also partially prevented cell injury, Ca(2+) overload and ER stress in animal and cell culture models. Therefore, ER stress is implicated in peripheral neuropathy in animal and cell culture models of T2DM. Prophylactic GSPs treatment might have auxiliary preventive potential for DPN partially by alleviating ER stress.