Molecular Iodine Supplement Prevents Streptozotocin-Induced Pancreatic Alterations in Mice.

Pancreatitis has been implicated in the development and progression of type 2 diabetes and cancer. The pancreas uptakes molecular iodine (I2), which has anti-inflammatory and antioxidant effects. The present work analyzes whether oral I2 supplementation prevents the pancreatic alterations promoted by low doses of streptozotocin (STZ). CD1 mice (12 weeks old) were divided into the following groups: control; STZ (20 mg/kg/day, i.p. for five days); I2 (0.2 mg/Kg/day in drinking water for 15 days); and combined (STZ + I2). Inflammation (Masson's trichrome and periodic acid-Schiff stain), hyperglycemia, decreased ß-cells and increased α-cells in pancreas were observed in male and female animals with STZ. These animals also showed pancreatic increases in immune cells and inflammation markers as tumor necrosis factor-alpha, transforming growth factor-beta and inducible nitric oxide synthase with a higher amount of activated pancreatic stellate cells (PSCs). The I2 supplement prevented the harmful effect of STZ, maintaining normal pancreatic morphometry and functions. The elevation of the nuclear factor erythroid-2 (Nrf2) and peroxisome proliferator-activated receptor type gamma (PPARγ) contents was associated with the preservation of normal glycemia and lipoperoxidation. In conclusion, a moderated supplement of I2 prevents the deleterious effects of STZ in the pancreas, possibly through antioxidant and antifibrotic mechanisms including Nrf2 and PPARγ activation.

Hypoglycemic activity of Codonopsis pilosula (Franch.) Nannf. in vitro and in vivo and its chemical composition identification by UPLC-Triple-TOF-MS/MS.

Codonopsis pilosula (Franch.) Nannf. (CPN), mainly planted in the northwest region, is a traditional Chinese medicine/good health food for nourishing qi and promoting blood circulation. This study firstly evaluated the inhibitory effects of the CPN extraction (CPNE) on α-glucosidase in vitro and in vivo, and tentatively confirmed its chemical ingredients by employing UHPLC-Triple-TOF-MS/MS. The CPNE had strong inhibitory activities against mammalian α-glucosidase (sucrase and maltase) and yeast α-glycosidase with semi-inhibitory concentrations (IC50) of 0.241 mg mL-1, 0.326 mg mL-1 and 1.167 mg mL-1, respectively. In addition, the CPNE could significantly decrease the postprandial blood glucose (PBG) levels in the sucrose/maltose/starch tolerance assays of diabetic mice. Furthermore, a total of 29 compounds, including 3 alkaloids, 13 phenolic acids, 8 alcohol glycosides and 5 alkynosides, were assigned based on comparison with the standards and references, as well as the analysis of main fragments. These results demonstrated that CPN could be used as an adjuvant therapy or dietary supplements to effectively control the occurrence and development of diabetes.

The impact of a novel Chinese yam-derived polysaccharide on blood glucose control in HFD and STZ-induced diabetic C57BL/6 mice.

Chinese yam, as a kind of traditional "medicine and food homologous food" in Asia, could assistance to digestion, nourish the lungs and relieve cough. Some research also suggested that Chinese yam could prevention of hyperglycemia, but the specific mechanism of action was not clear. In this paper, an acidic polysaccharide (CYPB) was isolated from Chinese yam with the molecular weight of 1.55 × 102 kDa. The determination of the monosaccharide composition of CYPB with ion chromatography showed that CYPB was composed of rhamnose, glucose, arabinose, galactose, glucose, xylose and glucuronic acid with the ratio of 6 : 3.73 : 7.31 : 10.95 : 4.56 : 1. The structural analysis indicated that the CYPB contain 1 → 3, 1 → 4, 1 → 2, 1 → 6 and 1 → 3, 6 glycoside bonds. The experimental results of diabetic mice model induced by high-fat diet (HFD) and streptozocin (STZ) indicated that CYPB could improve clinical symptoms and alleviate the glucose tolerance damage symptoms effectively. The underlying mechanism of regulate blood glucose of CYPB may be related to improve the ability of synthesize glycogen, insulin resistance and reduce gluconeogenesis by regulating the expression of InsR, PI3K, Akt and FoxO3, GLUT4 proteins in PI3K/Akt signaling pathway in T2DM mice.

Diaphragma juglandis extracts modifies the gut microbiota during prevention of type 2 diabetes in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The diaphragma juglandis (DJ) comes from the wooden septum in the core of Juglans regia L, also known as the walnut septum. In Iranian traditional medicine, walnut distraction wood was widely used in the treatment of diabetes. However, there is a lack of research data on the mechanism of DJ against diabetes. AIM OF THE STUDY: To explore the protective effect of diaphragma juglandis extract (DJE) on type 2 diabetic rats and the hypoglycemic mechanism of DJE. MATERIAL AND METHODS: Supplemented DJE and fed a high-fat diet for five weeks, and then injected low-dose STZ, successfully induced type 2 diabetic rats. Collected rat serum, liver, pancreas and feces to determine the biochemical parameters of serum and liver, analyze the pathological damages of pancreas and liver, and measure the changes of gut microbes in feces. RESULTS: DJE could inhibit the metabolic abnormalities of T2DM by improving insulin resistance, abnormal lipid metabolism, liver damage, oxidative stress, and reducing inflammation. DJE significantly held fasting blood glucose, glycosylated serum protein, serum low density lipoprotein, high density lipoprotein, oral glucose tolerance test, nitric oxide, superoxide dismutase and catalase, serum and liver triglycerides, total cholesterol, aspartate aminotransferase, alanine aminotransferase, malondialdehyde, lipopolysaccharide, fasting insulin and tumor necrosis factor-α and prevented the pathological damage of pancreas and liver. The 16SrRNA gene sequencing results showed that DJE intercepted the disorders of the fecal gut microbes, mainly including Lactobacillaceae, Rikenella, Pygmaiobacter, Oscillospiraceae and Klebsiella. Spearman correlation analysis showed that the changes of gut microbes were closely relative with biochemical parameters. CONCLUSION: DJE might prevent type 2 diabetes and its complications and hold up the disorders of gut microbes.

Anti-diabetogenic and in vivo antioxidant activity of ethanol extract of Dryopteris dilatata in alloxan-induced male Wistar rats.

AIMS: Oxido-inflammatory stress has been implicated as the main targets in alleviating diabetic complications induced by hyperglycaemia. Dryopteris dilatata: a bioactive plant serves great medicinal benefits in ethnopharmacology to ameliorate pathological conditions. This study investigated the protective effects of ethanol extract of Dryopteris dilatata (EEDD) in alloxan-induced diabetic rats through mechanism involving inhibition of oxidative stress and liver and kidney inflammatory markers. METHODOLOGY: Male Wistar rats were made diabetic via alloxan monohydrate (100 mg/kg) administration intraperitoneally. Diabetic rats were post-treated with EEDD (800 mg/kg) and Metformin (50 mg/kg) orally for two weeks. Fasting blood sugar (FBS), body and organ weight change, markers of oxidative stress, liver and kidney inflammation were evaluated. RESULTS: Our results revealed that EEDD significantly reduced alloxan-induced hyperglycaemia in the diabetic rats after 5, 10 and 15 days of treatment. Markers of oxidative injury were also significantly ameliorated in the pancreas, liver and kidney of the diabetic rats following treatment with EEDD. However, liver and kidney injury markers were significantly attenuated with marked decreased organ weight in the diabetic rats after treatment with EEDD. CONCLUSION: Here in, we found that Dryopteris dilatata could be used as nutraceuticals in the prevention and treatment of diabetes and its related complications through positively modulating oxidative stress and liver and kidney inflammatory markers.

Biochemical Evidence Indicates the Preventive Effect of Resveratrol and Nicotinamide in the Treatment of STZ-induced Diabetic Cataract.

PURPOSE: High glucose level is a strong initiator of both oxidative stress and DNA damage to various cellular proteins. This activates the poly ADP-ribose polymerase (PARP) enzyme, which is responsible for disturbing physiological energy metabolic homeostasis. The present study aimed to elucidate the association between stress and the PARP pathway by using resveratrol (RSV) and nicotinamide (NAM, PARP inhibitor) to treat diabetic cataract. METHOD: Albino rats were used for the experimental study. A single streptozotocin administration (55 mg/kg, i.p.) prompted diabetes in the animals. The experimental groups were the normal group (non-diabetic) and the diabetic groups: the diabetic control animals (group D), the diabetic animals treated with RSV at 40 mg/kg/day, i.p. (D+ RSV group), NAM at 100 and 300 mg/kg/day, i.p. (D+ NAM100, D+ NAM300 groups, respectively), and a combination of RSV and NAM i.p. (D+ RSV+NAM100 = Combi 1 group, D+ RSV+NAM300 = Combi 2 group). Glucose levels and the eyes were examined biweekly; various cataractogenic parameters in the lenses were examined after completion of the eight-week experimental protocol. RESULTS: Compared to diabetic control, RSV monotherapy significantly decreased hyperglycemia and other lenticular alterations. NAM at the high dose only showed beneficial effects without altering the blood glucose level, lenticular aldose reductase (AR) activity, and sorbitol content, primarily restored the lenticular NAD level and decreased oxidative stress in diabetic rats. These findings regarding NAM treatment indicate that a pathway other than the antioxidant defense system and the polyol pathway, which might be due to PARP inhibition, is involved in diabetic cataracts. Moreover, compared to RSV monotherapy, combination treatments were effective. CONCLUSION: These results indicate that hyperglycemia and oxidative-osmotic-nitrosative stress play central roles in the pathophysiology of diabetic cataracts. Moreover, our study also revealed that concurrent treatment with the RSV and NAM may prove useful in the pharmacotherapy of diabetes and its secondary complications such as cataract.

Pinoresinol-4-O-ß-D-glucopyranoside: a lignan from prunes (Prunus domestica) attenuates oxidative stress, hyperglycaemia and hepatic toxicity in vitro and in vivo.

OBJECTIVES: This study aimed to explore the pharmacological properties of pinoresinol-4-O-ß-D-glucopyranoside (PG), isolated from prunes. METHODS: In-vitro antioxidant activity was assessed using ferric reducing antioxidant power (FRAP) and 2,2'-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS) assays. In-vivo hepatoprotective activity was evaluated using CCl4 -induced hepatotoxicity mouse model. The antihyperglycaemic activity was determined in vitro using α-glucosidase and α-amylase inhibiting activity and in vivo using streptozotocin-treated model. Molecular modelling was done on α-amylase, α-glucosidase, aldose reductase and peroxisome proliferator-activated receptor gamma. KEY FINDINGS: Pinoresinol-4-O-ß-D-glucopyranoside showed promising antioxidant activity in FRAP and ABTS assays with total antioxidant capacity equal 418.47 and 1091.3 µmol/g in terms of ascorbic acid, respectively. PG (50 mg/kg b.w.) exhibited a hepatoprotective activity in vivo as it lowered AST and ALT levels. PG showed a potent in-vitro antihyperglycaemic activity as it inhibited α-glucosidase with an IC50 value of 48.13 µg/ml. PG caused a prominent decline in serum glucose level by 37.83% in streptozotocin-treated mice with promising elevation in insulin level of 25.37%. Oxidative stress markers were reduced by PG, and it showed a high fitting on α-amylase and α-glucosidase active sites. CONCLUSIONS: Pinoresinol-4-O-ß-D-glucopyranoside is a natural entity combating oxidative stress, hepatic damage and diabetes.

Potential of Moringa oleifera to Improve Glucose Control for the Prevention of Diabetes and Related Metabolic Alterations: A Systematic Review of Animal and Human Studies.

Moringa oleifera (MO) is a multipurpose plant consumed as food and known for its medicinal uses, among others. Leaves, seeds and pods are the main parts used as food or food supplements. Nutritionally rich and with a high polyphenol content in the form of phenolic acids, flavonoids and glucosinolates, MO has been shown to exert numerous in vitro activities and in vivo effects, including hypoglycemic activity. A systematic search was carried out in the PubMed database and reference lists on the effects of MO on glucose metabolism. Thirty-three animal studies and eight human studies were included. Water and organic solvent extracts of leaves and, secondly, seeds, have been extensively assayed in animal models, showing the hypoglycemic effect, both under acute conditions and in long-term administrations and also prevention of other metabolic changes and complications associated to the hyperglycemic status. In humans, clinical trials are scarce, with variable designs and testing mainly dry leaf powder alone or mixed with other foods or MO aqueous preparations. Although the reported results are encouraging, especially those from postprandial studies, more human studies are certainly needed with more stringent inclusion criteria and a sufficient number of diabetic or prediabetic subjects. Moreover, trying to quantify the bioactive substances administered with the experimental material tested would facilitate comparison between studies.

Fruiting Bodies of Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes) Alleviate Diabetes-Associated Oxidative Stress.

Hyperglycemia-induced complications, the major causes of death in diabetes, are closely related to the elevated oxidative stress. Our previous study indicated that fruiting bodies of Ophiocordyceps sinensis attenuated polydipsia and hyperglycemia in diabetic rats. In this study, we further investigated whether the protective effects of O. sinensis on diabetes are associated with improved oxidative status in the circulation and target organs, the liver and kidneys. Male Wistar rats were fed with a semipurified diet supplemented with fruiting bodies (FB group, 1 g/day), carcass (CC group, 1 g/day), fruiting bodies and carcass (CF group, each 0.5 g/day), or placebo (DM and R groups) for 4 weeks (day 1 to 29). On day 15, animals were injected with nicotinamide (200 mg/kg) and streptozotocin (65 mg/kg) to induce diabetes. After the induction of diabetes, fasting blood glucose (FBG) was increased and the diabetes-increased FBG (day 15 to 26) was alleviated by the supplementation of fruiting bodies (p < 0.05, one-way ANOVA). In addition, the contents of vitamins A and C in the liver were significantly higher in the FB group, and the contents of glutathione in the liver and vitamin A and C in the kidneys were significantly higher in the FB, CC, and CF groups than in the DM group. The diabetes-increased glutathione peroxidase activity in the liver was decreased in the CF group. These results suggest that O. sinensis, especially fruiting bodies, may have antihyperglycemic activity associated with the alleviated oxidative stress in the liver and kidneys.

Scutellariae radix and coptidis rhizoma ameliorate glycolipid metabolism of type 2 diabetic rats by modulating gut microbiota and its metabolites.

Scutellariae radix (Scutellaria baicalensis Georgi, SR) and coptidis rhizoma (Coptis chinensis Franch, CR) are both widely used traditional Chinese medicines and have been used together to treat T2DM with synergistic effects in the clinical practices for thousands of years, but their combination mechanism is not clear. Accumulating evidences have implicated gut microbiota as important targets for the therapy of T2DM. Thus, this study aimed to unravel the cooperation mechanism of SR and CR on the amelioration of T2DM based on the systematic analysis of metagenome and metabolome of gut microbiota. Bacterial communities were analyzed based on high-throughput 16S rRNA gene sequencing. Furthermore, ultra high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) was used to analyze variations of microbial metabolites in feces and the contents of short chain fatty acids (SCFAs) in the cecum were determined by a gaschromatography-flame ionization detector (GC-FID). 16S rRNA gene sequencing results revealed that T2DM rats treated with SR, CR, and the combination of SR and CR (SC) exhibited changes in the composition of the gut microbiota. The SCFAs-producing bacteria such as Bacteroidales S24-7 group_norank, [Eubacterium] nodatum group, Parasutterella, Prevotellaceae UCG-001, Ruminiclostridium, and Ruminiclostridium 9 in T2DM rats were notably enriched after treatment with SR, CR, and their combination. In contrast, secondary bile acid-producing bacteria such as Escherichia-Shigella strongly decreased in numbers. The perturbance of metabolic profiling in T2DM rats was obviously improved after treatment, exhibiting a lower level of secondary bile acids and a numerical increase of microbially derived SCFAs. Moreover, the correlation analysis illustrated a close relationship among gut microbiota, its metabolites, and T2DM-related indexes. The findings indicated that the crosstalk between microbiota-derived metabolites and the host played an important role in the progress of T2DM and might provide a novel insight regarding gut microbiota and its metabolites as potential new targets of traditional Chinese medicines. Furthermore, this work also suggested that the integration of various omics methods and bioinformatics made a useful template for drug mechanism research.

Effect of garden cress in reducing blood glucose, improving blood lipids, and reducing oxidative stress in a mouse model of diabetes induced by a high-fat diet and streptozotocin.

BACKGROUND: A mouse model in which diabetes mellitus was induced by low-dose streptozotocin (STZ) injection combined with a high-fat diet was used to study the effect of two water cress (Lepidium savitum) preparations. Diabetic mice were treated with dried cress powder or with water-soluble extracts (tested at two doses), together with proper control groups. The mice were evaluated after 4 weeks of continuous intervention for type 2 diabetic and associated markers. We determined blood glucose, body weight, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), serum insulin levels, and DNA integrity of hepatic cells. The concentrations of malondialdehyde (MDA) and lipid peroxide (LPO) and the activities of four enzymes that are part of the antioxidant defense system were determined in liver samples, as well as gene expression (by semi-quantitative reverse transcription polymerase chain reaction) and enzyme activity of IRS-1, IRS-2, PI3K, AKT-2, and GLUT4. RESULTS: After 4 weeks of intervention, the levels of TC, TG, and LDL cholesterol were significantly (P < 0.5) decreased and HDL cholesterol was significantly increased. Enzyme activities of liver superoxide dismutase, glutathione, glutathione peroxidase, and catalase were significantly increased, whereas MDA and LPO concentrations were significantly reduced. The transcription level of the five genes assessed was increased, with corresponding increases in protein expression. CONCLUSION: Oral uptake of garden cress can significantly reduce the blood glucose and improve the blood lipid metabolism of diabetic mice. Considerable improvements in the activity of antioxidant defense enzymes were observed in type 2 diabetic mice that improved the body's antioxidant emergency response. © 2019 Society of Chemical Industry.

Protective efficacy of Tinospora sinensis against streptozotocin induced pancreatic islet cell injuries of diabetic rats and its correlation to its phytochemical profiles.

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora sinensis Lour. (Merr.) belongs to the family Menispermaceae and its stem extract have been used traditionally in broad aspects of therapeutic remedies including debility, dyspepsia, fever, jaundice, ulcer, bronchitis, urinary disease, skin disease, liver disease and diabetes. AIM OF THE STUDY: The aim of the study was to evaluate the protective effects of methanol extract of stem of Tinospora sinensis (METS) on streptozotocin induced pancreatic islet cell injuries of diabetic rats and its correlation to its phytochemical profiles. MATERIALS AND METHODS: A high-performance liquid chromatography technique (HPLC) was used to identify and quantify the major phytochemicals present in the METS. Diabetic rats were administered with METS at a dose of (100, 200 and 400 mg/kg respectively orally) and standard drug Metformin (300 mg/kg) was given orally to group serving positive control. Effect of the METS on glucose homeostasis, oxidative stress, antioxidant status, histopathology of pancreas and also on intracellular reactive oxygen species (ROS), mitochondrial membrane potential, apoptosis, cell cycle of pancreatic islet cells were studied in diabetic rats. RESULTS: The major phytochemicals identified and quantified by HPLC in the extract were berberine, caffeic acid, myricetin and ferulic acid. This result showed that methanol extract exhibited good antioxidant effect. The methanol extract of the plant prevented the diabetogenic effect of STZ and significantly lowered the fasting blood glucose level, glycated haemoglobin and increased insulin and C-peptide level in treated rats. METS reduced apoptosis of STZ treated islet cells by significantly decreasing pro-inflammatory cytokines (TNFα, IL6), intracellular ROS generation, lipid peroxidation, nitric oxide (NO) production and increasing mitochondrial membrane potential and sub-G0 peak area, enzymatic and nonenzymatic antioxidants. CONCLUSION: The results revealed that the methanol extract of the stem of the plant possesses protective effects against diabetes and associated complications.

Effect of Marantodes pumilum Blume (Kuntze) var.alata on ß-cell function and insulin signaling in ovariectomised diabetic rats.

BACKGROUND: Oestrogen deficiency leads to metabolic disturbances such as insulin resistance and impairment of adipose tissue or lipid metabolism. Marantodes pumilum (Blume) Kuntze (Primulaceae) is believed to have phytoestrogenic properties and is claimed to have beneficial effects in the treatment of diabetes mellitus (DM), but the mechanism behind its phytoestrogenic effects on estrogen-deficient diabetic condition have not been fully examined. PURPOSE: The present study investigated the effects of oral treatment with M. pumilum var. alata (MPA) extracts on the estrogen receptor, metabolic characteristics and insulin signaling pathway in pancreas and liver of ovariectomised nicotidamide streptozotocin-induced diabetes in female rats. MATERIALS AND METHODS: Ovariectomised diabetic (OVXS) Sprague-Dawley rats were orally administered with either aqueous leaf extract and ethanol (50%) stem-root extract of MPA (50 or 100 mg/kg) respectively for 28 days. Metabolic parameters were evaluated by measuring fasting blood glucose, serum insulin, oral glucose and insulin tolerance test. Distribution and expression level of insulin, oxidative stress and inflammatory marker in the pancreatic islets and liver were evaluated by immunohistochemistry and western blot, respectively. RESULTS: Oral treatment with aqueous leaf and ethanol (50%) stem-root extracts of MPA (100 mg/kg) significantly reversed the elevated fasting blood glucose, impaired glucose and insulin tolerance. The protein expression of insulin, glucose transporter (GLUT-2 and GLUT-4) increased in the pancreatic islets and liver. Furthermore, marked improvement in the tissue morphology following treatment with MPA was observed. Similarly, the western blots analysis denotes improved insulin signaling in the liver and decreased reactive oxygen species producing enzymes, inflammatory and pro-apoptotic molecules with MPA treatment. CONCLUSIONS: Taken together, this work demonstrate that 100 mg/kg of aqueous leaf extract and ethanol (50%) stem-root extract of MPA improves ß-cell function and insulin signaling in postmenopausal diabetes through attenuation of oxidative stress and partially mediated by oestrogen receptor stimulation.

Anti-Lipid Peroxidation, α-Glucosidase and α-Amylase Inhibitory Effects of the Extract of Capitula of Coreopsis tinctoria Nutt. and Protection Effects on High-Fat/High-Sugar and Streptozotocin-Induced Type 2 Diabetes in Mice.

Coreopsis tinctoria capitula (CTC) of the Compositae family has been used traditionally to treat various diseases in China, particularly type 2 diabetes mellitus (T2DM). This study evaluated the anti-lipid peroxidation, α-glucosidase and α-amylase inhibitory effects of CTC extracts, and analyzed its chemical composition by HPLC. Moreover, the antioxidant activity and protection effects of CTC extracts were investigated on high-fat/high-sugar and streptozotocin-induced T2DM mice. In vitro study, the ethyl acetate extract (EAE) and butanol extract (BE) of CTC exhibited anti-lipid peroxidation (IC50 : BHA>BE or EAE>ascorbic acid, p<0.05) and α-glucosidase inhibitory activity (IC50 : BE>EAE, p<0.05). In vivo, the BE at the dose of 600 mg/kg was intragastrically given to T2DM mice, which exhibited a certain extent of repair and improvement of the levels of CAT, GSH, GSH-PX , SOD, as well as plasma biomarkers, compared with those in the model group (p<0.05). These results demonstrated that CTC extracts have a positive effect to treat T2DM and it can be used for the treatment of T2DM in the future.

Tetramethylpyrazine prevents diabetes by activating PI3K/Akt/GLUT-4 signalling in animal model of type-2 diabetes.

AIMS: The present experiment was conceptualised to explore the therapeutic response of tetramethylpyrazine (TMP), a major active constituent of Ligusticum chuanxiong, a Chinese traditional medicinal plant, in high-fat diet (HFD)-streptozotocin (STZ)-induced diabetes in rats and to identify the possible mechanism of action. MAIN METHODS: Dose-reliant effect of oral treatment of TMP (100, 150 and 200 mg/kg/day) for 28 days was evaluated by calculating the alteration in body weight, level of fasting blood glucose (FBG), plasma insulin, homeostasis model assessment (HOMA), serum lipids, oral glucose & intraperitoneal insulin tolerance and glycosylated haemoglobin in HFD-STZ-induced type-2 diabetic (T2D) rats and underlying molecular mechanisms of TMP was also studied. KEY FINDINGS: TMP treatment prominently reduced the level of FBG, glycosylated haemoglobin and revived body weight gain and level of serum insulin dose-dependently in diabetic rats. TMP treatment considerably improved insulin resistance, as observed in oral glucose tolerance and insulin tolerance tests. Moreover, dose-dependent reduction in the level of pro-inflammatory cytokines, C-reactive protein (CRP) and interleukin-6 (IL-6) was observed and their level was found to be significantly reduced in highest dose TMP (200 mg/kg) treated diabetic rats, pointing towards TMP mediated recovery of insulin signalling and a decrease in insulin resistance. The expressions of p-PI3K-p85/p-Akt/GLUT-4 were also significantly up-regulated by TMP (200 mg/kg), suggesting the connection of the PI3K/Akt signal pathway in the anti-hyperglycemic action of TMP. SIGNIFICANCE: These findings suggest that TMP may be used as a potential agent for type-2 diabetes treatment.

Green Tea Ameliorates Hyperglycemia by Promoting the Translocation of Glucose Transporter 4 in the Skeletal Muscle of Diabetic Rodents.

It is known that green tea helps prevent obesity and diabetes mellitus. In this study, we aimed to determine whether green tea ameliorates hyperglycemia and the mechanism involved in diabetic rodents. Green tea consumption reduced blood glucose and ameliorated glucose intolerance, which was assessed using an oral glucose tolerance test in both streptozotocin-induced type 1 diabetic rats and type 2 diabetic KK-Ay mice. Green tea also reduced the plasma fructosamine and glycated hemoglobin concentrations in both models. Furthermore, it increased glucose uptake into the skeletal muscle of both model animals, which was accompanied by greater translocation of glucose transporter 4 (GLUT4). Moreover, epigallocatechin gallate (EGCG), the principal catechin in green tea, also ameliorated glucose intolerance in high-fat diet-induced obese and diabetic mice. These results suggest that green tea can ameliorate hyperglycemia in diabetic rodents by stimulating GLUT4-mediated glucose uptake in skeletal muscle, and that EGCG is one of the effective compounds that mediate this effect.

Effect of Fenofibrate on the Expression of Inflammatory Mediators in a Diabetic Rat Model.

Purpose: To investigate the mechanisms of anti-inflammatory and anti-oxidative effects of fenofibrate, a peroxisome proliferator-activated receptors-α agonist, in preventing diabetic retinopathy (DR) progression via a diabetic rat model. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin in 6-week-old female Wistar rats. Diabetic rats were divided into diabetes without treatment (n = 10), diabetes treated with low dose fenofibrate (30 mg/kg/day) (n = 10) and high dose fenofibrate (100 mg/kg/day) (n = 10). Serum aqueous humor (AqH) and ocular tissues were gathered after 3-month treatment. Expressions of NF-κB and inflammatory chemokines (monocyte chemoattractant protein-1, fractalkine, and intercellular adhesion molecule-1) were detected by reverse transcription-polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and electrophoretic mobility shift assay. The levels of oxidative biomarkers, including acrolein, nitrotyrosine, and 8-hydroxy-2'-deoxyguanosin (8-OHdG), were determined by IHC and ELISA. The reactive oxygen species (ROS) levels in serum and AqH were measured by chemiluminescence methods. Results: After 3 months of treatment, the expressions of mRNA and protein of monocyte chemoattractant protein-1, fractalkine, and intercellular adhesion molecule-1 in the retina of diabetic rats were significantly inhibited by fenofibrate in a dose-dependent manner. These effects were mediated by inhibition of NF-κB by fenofibrate. The levels of oxidative markers, including acrolein, nitrotyrosine, and 8-OHdG, decreased in the retina of diabetic rats after fenofibrate treatment. The ROS levels in the AqH of diabetic rats also suppressed by fenofibrate. Conclusions: Fenofibrate significantly inhibited the expressions of NF-κB and inflammatory chemokines and reduced oxidative products within diabetic retina. Treatment of fenofibrate might be beneficial to preventing DR progression.

Mangosteen Vinegar Rind from Garcinia mangostana Prevents High-Fat Diet and Streptozotocin-Induced Type II Diabetes Nephropathy and Apoptosis.

Type II diabetes (T2D) nephropathy, a major cause of end-stage kidney disease, progresses and develops from oxidative stress. Natural polyphenols can protect the kidney from diabetic nephropathy exerting antioxidant activities. The present approach enumerates the reno-protective and anti-apoptotic effects of mangosteen vinegar rind (MVR, a phenolic aqueous extract) against high-fat diet (5 g/day up to five weeks)-/streptozotocin (single ip, dose 30 mg/kgBW)-induced T2D nephropathy of albino mice. In vitro total phenolic content, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant capacity, and α-amylase inhibition activity as antidiabetic assay of MVR were performed. In vivo mice body weight, oral glucose, and maltose tolerance test, metabolic parameters (plasma glucose, insulin level, omeostasis model assessment-estimated insulin resistance), biochemical parameters (kidney hypertrophy, blood urea nitrogen, creatinine), oxidative stress parameters (malondialdehyde, superoxide dismutase, catalase) were estimated in an intervention study. Additionally, renal morphology and early apoptosis were observed following the H & E staining and TUNEL assay of the tissue frozen section. We found that the aqueous extract of MVR possesses potent in vitro antioxidative and antidiabetic activities. Animal intervention results showed that MVR 100, 200 mg/kgBW, and Glibenclamide 60 mg/kgBW treatments significantly improved (P < 0.05) the abovementioned parameters compared to the diabetic control group. Furthermore, treatments also significantly restored (P < 0.05) kidney histological alterations and reduced cellular apoptosis compared to the diabetic control group. These findings concluded that MVR treatments significantly modulated the glucose intolerance, metabolic alterations, and oxidative stress-induced pathological alterations and cellular apoptosis of diabetic kidney. PRACTICAL APPLICATION: Garcinia mangostana, a polyphenol rich natural product, is obtained from the tropical rain forest area of Southeast Asian countries and processes diverse biological activities including antioxidant, anti-proliferative, anti-inflammatory, anti-carcinogenic, and so on. This research first time focuses on the nephro-protective and anti-apoptotic effects of mangosteen vinegar rind (MVR) from the mangosteen fruit pericarp. Our study provides the efficient data to prove the beneficial effect of MVR as a dietary supplement for the prevention and management of diabetic nephropathy.

Antidiabetic Effects of a Short Peptide of Potato Protein Hydrolysate in STZ-Induced Diabetic Mice.

Alcalase- generated potato protein hydrolysate (APPH) is a potential bioactive peptide against diabetes mellitus (DM) and DM-associated secondary effects in animal models. The aim of the present study was to find the efficiency of a deca-peptide DIKTNKPVIF (DF) from APPH against DM. Six-week-old male ICR mice were divided into the following groups: Control, Control+DF (received 50 mg/kg DF), streptozotocin (STZ)-induced DM group, DM+Acarbose group (20 mg/kg of acarbose), DM+DF-L (25 mg/kg of DF), DM+DF-H (50 mg/kg of DF), and DM+APPH (50 mg/kg of APPH). Comparable to APPH, treatment with DF effectively regulated blood glucose level and also controlled plasma total glycerol (TG), total cholesterol (TC), insulin, and HbA1c levels in DM animals. DF treatment also showed evidence of ameliorating DM-associated damages in the pancreatic islets and in the liver, heart, and kidney tissues. Therefore, the results demonstrate that the short synthetic peptide-DF may effectively provide protection against DM-associated damages.

Heat-Shock Protein 70-Mediated Heat Preconditioning Attenuates Hepatic Carbohydrate and Oxidative Disturbances in Rats With Type 1 Diabetes.

OBJECTIVES: Heat preconditioning and heat-shock protein (HSP) synthesis have significant cytoprotective effects against the development of cellular injury caused by the application of a subsequent stressor, which were found to depend on the time period between the stressors. We aimed to determine the most efficient recovery time (6 h or 24 h) following heat-stress exposure and prior application of diabetic streptozotocin (STZ) on the moderation of carbohydrate and oxidative metabolic disturbances caused by diabetes. METHODS: Experiment animals (Wistar rats) were exposed to acute heat stress at 41±1°C for 45 min, followed by 6-h or 24-h recovery times at room temperature before sacrifice or STZ administration. RESULTS: Our findings indicate that acute heat stress with 6-h or 24-h recovery periods results in a significant rise in the hepatic heat-shock protein 70 (HSP70) levels (even more so after 24 h), glycogen breakdown and stable glycemia, followed by reduced glycolytic and gluconeogenic activity (after 24 h) (glucose-6-phosphatase, fructose-1,6-bisphosphatase); stimulates antioxidative activity (glutathione peroxidase, glutathione reductase) (after 6 h); and decreases glutathione and catalase activity (after 24 h). Heat preconditioning (with 6-h and 24-h recovery periods) prior to STZ-induced diabetes increases HSP70 levels and causes lower serum glucose levels, higher glycogen and glucose-6-phosphate levels, lower glucose-6-phosphatase levels and glycogen phosphorylase and hexokinase levels but also elevates glutathione reductase and glutathione peroxidase activity compared to untreated STZ animals. CONCLUSIONS: Based on our findings, heat preconditioning and HSP70 induction in rats with type 1 diabetes attenuates STZ-induced metabolic alterations in hepatic carbohydrate metabolism and oxidative states. These changes are more evident at 24 h recovery post-acute heat stress, based on the most evident accumulation of HSP70 in this time frame.