clove and Insulin-Resistance

Psidium guajava L. leaves are used to treat diabetes in South African folkloric medicine and in other parts of the world. Psidium x durbanensis Baijnath & Ramcharun ined. (PD) is a natural sterile hybrid and congener of Psidium guajava that is expected to share the medicinal properties of the genus Psidium and is widely distributed in South Africa.. This study investigates the antioxidant, antidiabetic effects, and mechanisms of action of hydro-methanolic leaf extracts of PD on streptozotocin-induced diabetes in rats.. Phytochemical constituents of hydro-methanolic extract of PD were analyzed by gas chromatography-mass spectrometry (GC-MS). Male Wistar rats 250-300 g body weight (BW) were rendered diabetic after a single intraperitoneal injection with streptozotocin, 45 mg/kg BW. The diabetic rats were treated with hydro-methanolic (20:80 v/v) leaf extracts of PD (400 mg/kg/BW) or subcutaneous injections of regular insulin (2.0U/kg/BW, bid) for 56 days. The body weights of the animals were recorded daily. Fasting blood glucose, glucose tolerance tests, and insulin resistance index were measured. The effects of the extracts on total superoxide dismutase, catalase, and reduced glutathione activities, histopathology, and gene expression of insulin receptor substrate 1 and glucose transporter 4 were determined in the liver, pancreas, and gastrocnemius muscles of the rats.. In the acute toxicity studies, there were no signs of toxicity observed for PD up to 2000 mg/kg BW doses. Diabetic animals showed significant weight loss, elevated and reduced fasting blood glucose and insulin, respectively, impaired glucose tolerance and diminished antioxidant enzymes' activities compared to controls. Treatment with PD hydro-methanolic leaf extracts improved body weight, glucose tolerance, insulin resistance, and antioxidant enzymes but not plasma insulin in diabetic animals compared to controls, respectively. GC-MS analysis identified organic acids, alcohols, vitamins, terpenoids, and esters in the extracts. Treatment with PD improved glucose uptake by stimulating mRNA expression of GLUT 4 in gastrocnemius muscles of diabetic animals compared to the untreated control and also restored histological aberrations in the pancreas and liver of diabetic rats compared with the untreated control rats.. Collectively, the present study suggests that treatment with PD leaf extracts significantly ameliorated diabetes symptoms and oxidative stress in rats, and these effects may be linked to the bioactive phytoconstituents present in the plant. This study further suggests that PD improves insulin resistance by increasing glucose uptake in gastrocnemius muscles in an insulin-independent manner.

Topics: Animals; Antioxidants; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Hypoglycemic Agents; Insulin; Insulin Resistance; Myrtaceae; Plant Extracts; Psidium; Rats; Rats, Wistar; Streptozocin

Polyphenols from cambuci (CBC) (Campomanesia phaea (O. Berg.)), a Brazilian native fruit, were investigated on therapeutic actions mitigating insulin resistance and hepatic steatosis in high-fat-sucrose diet (HFS) induced obese mice. For this, C57BL/6J mice fed with a obesogenic and diabetogenic HFS diet were administered with either water or two CBC doses (36 or 74 mg gallic acid equivalent (GAE)/kg body weight) by gavage from week 6 to week 14 (end-point) of HFS feeding. CBC reduced body weight gain, inflammation, hepatic steatosis, hyperglycemia, glucose intolerance, and insulin resistance in liver and skeletal muscle of obese mice, and such effects were associated with activation of Akt and AMPK in these tissues. In conclusion, polyphenols from CBC show important therapeutic actions ameliorating obesity-associated complications.

Topics: Animals; Diet, High-Fat; Fruit; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Myrtaceae; Non-alcoholic Fatty Liver Disease; Obesity; Polyphenols

Some polyphenols have been reported to modulate the expression of several genes related to lipid metabolism and insulin signaling, ameliorating metabolic disorders. We investigated the potential for the polyphenols of two varieties of grumixama, the purple fruit rich in anthocyanins and the yellow fruit, both also rich in ellagitannins, to attenuate obesity-associated metabolic disorders. Mice were fed a high fat and high sucrose diet, supplemented daily with yellow and purple extracts (200 mg per kg of body weight) for eight weeks. Purple grumixama supplementation was found to decrease body weight gain, improve insulin sensitivity and glucose-induced hyperinsulinemia, and reduce hepatic triglyceride accumulation. A decrease in intrahepatic lipids in mice treated with the purple grumixama extract was associated with lipid metabolism modulation by the PPAR signaling pathway. LPL, ApoE, and LDLr were found to be down-regulated, while Acox1 and ApoB were found to be upregulated. Some of these genes were also modulated by the yellow extract. In addition, both extracts decreased oGTT and plasma LPS. The results were associated with the presence of phenolic acids and urolithins. In conclusion, most likely the anthocyanins from the purple grumixama phenolic extract is responsible for reducing obesity and insulin resistance.

Topics: Animals; Anthocyanins; Diet, High-Fat; Disease Models, Animal; Eugenia; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Phytotherapy; Plant Extracts

Infusions of murtilla leaves exhibit antioxidant, analgesic, and anti-inflammatory properties. Several compounds that are structurally similar to madecassic acid (MA), a component of murtilla leaf extract (ethyl acetate extract, EAE), have been shown to inhibit protein tyrosine phosphatase 1B (PTP1P). The aim of this study was to evaluate if EAE and two compounds identified in EAE (MA and myricetin [MYR]) could have a beneficial effect on systemic and vascular insulin sensitivity and endothelial function in a model of diet-induced obesity. Experiments were performed in 5-week-old male C57BL6J mice fed with a standard (LF) or a very high-fat diet (HF) for 4 weeks and treated with EAE, MA, MYR, or the vehicle as control (C). EAE significantly inhibited PTP1B. EAE and MA, but not MYR, significantly improved systemic insulin sensitivity in HF mice and vascular relaxation to Ach in aorta segments, due to a significant increase of eNOS phosphorylation and enhanced nitric oxide availability. EAE, MA, and MYR also accounted for increased relaxant responses to insulin in HF mice, thus evidencing that the treatments significantly improved aortic insulin sensitivity. This study shows for the first time that EAE and MA could constitute interesting candidates for treating insulin resistance and endothelial dysfunction associated with obesity.

Topics: Animals; Aorta; Diet, High-Fat; Disease Models, Animal; Endothelium, Vascular; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Myrtaceae; Nitric Oxide; Nitric Oxide Synthase Type III; Obesity; Phosphorylation; Plant Extracts; Plant Leaves; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Proto-Oncogene Proteins c-akt; Triterpenes

This study investigated the effects of freeze-dried jaboticaba peel (FJP) and jaboticaba tea (JE) on obesity parameters of diet-induced obese rats. Thirty-six male Wistar rats were distributed into six groups: AIN-93 M feed a normal control diet; HFF (obese control) feed a high-fat and fructose diet; Prevention FJP (P. FJP) and Treatment FJP (T. FJP) feed HFF diet with 2% of FJP powder, for 12 and 6 weeks respectively; Prevention JE (P. JE) and Treatment JE (T. JE) were feed with HFF diet and the water was substituted by JE, for 12 and 6 weeks, respectively. Lipid profile, glucose, adiponectin and leptin were measured. Glucose and insulin tolerance, also pancreatic islet insulin secretion were determined. Liver morphology and fat liver accumulation were evaluated. Results showed that HFF-diet induced weight gain, dyslipidemia, glucose intolerance, insulin resistance and hepatic steatosis. All FJP and JE treatments reduced weight gain, adiposity and improved insulin sensitivity. Twelve weeks supplementation increased HDL-cholesterol and prevented hepatic steatosis. Our results suggest that FJP and JE act as functional foods, being a dietary strategy to prevent or control obesity. FJP and JE 12 weeks supplementation can modulate important parameters of obesity and insulin metabolism, preventing liver steatosis in obese rats.

Topics: Animals; Disease Models, Animal; Fatty Liver; Insulin Resistance; Male; Myrtaceae; Obesity; Plant Extracts; Powders; Rats; Rats, Wistar

Insulin resistance (IR) plays an important role in the development of many diseases, such as diabetes mellitus. Therefore, the aim of the present study was to evaluate the effects of the extracts from fruits native to Brazil on metabolic parameters and hepatic oxidative markers in an animal model of insulin resistance induced by dexamethasone (DEX).. Wistar rats received water or extracts of Eugenia uniflora or Psidium cattleianum, once a day for 21 days. For the last 5 days, the rats received an intraperitoneal injection of saline or DEX.. DEX caused a reduction in body weight gain and relative pancreatic weight, as well as glucose intolerance, and an increase in serum glucose and triacylglycerol levels. The extracts were found to prevent hyperglycemia and hypertriglyceridemia. DEX caused an increase in the levels of thiobarbituric acid-reactive substances and reactive oxygen species production in the liver of rats, and both extracts prevented these changes. In addition, hepatic glutathione peroxidase activity was reduced by DEX. However, total thiol content and activities of catalase, superoxide dismutase, and delta-aminolevulinate dehydratase were not altered in any of the tested groups.. Fruit extracts of E. uniflora and P. cattleianum exhibited considerable antihyperglycemic, antidyslipidemic, and antioxidant effects, and may be useful in the therapeutic management of alterations due to IR.

Topics: Animals; Antioxidants; Brazil; Dexamethasone; Disease Models, Animal; Dyslipidemias; Enzymes; Eugenia; Fruit; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Liver; Male; Oxidative Stress; Plant Extracts; Psidium; Rats, Wistar

The hyperphosphorylation of microtubule-associated protein tau (tau) in the hippocampus can be caused by central and peripheral insulin resistance and these alterations are related to the development of tauopathies, such as Alzheimer's disease. In this study, we used a high-fat diet to induce obesity and insulin resistance in adult Swiss mice and checked whether supplementation with Myrciaria jaboticaba berry peel for 10 weeks could improve insulin sensitivity, learning/memory performance, and prevent tau phosphorylation in the hippocampus. Furthermore, adipocytokines, inflammatory markers, and oxidative stress were assessed. Myrciaria jaboticaba peel has phenolic compounds (e.g., cyanidin, ellagic acid), dietary fiber and carotenoids, which contribute to great antioxidant capacity. Supplementation of the high-fat diet with 4% M. jaboticaba peel prevented fat weight gain and reduced peripheral insulin resistance. The treated group also showed lower tau phosphorylation in the hippocampus corroborating better learning/memory performance in the Morris water maze test. Maintenance of neuronal viability, lower levels of hippocampal inflammatory markers, and improved brain antioxidant defenses were also related to the consumption of M. jaboticaba peel. These findings contribute to a better understanding of how a high-fat diet supplemented with jaboticaba berry peel counteracts the impairment of cognitive functions caused by high-fat diet intake and diet-induced insulin resistance.

Topics: Animals; Anthocyanins; Biomarkers; Carotenoids; Cognition; Cytokines; Diet, High-Fat; Dietary Fiber; Ellagic Acid; Fruit; Hippocampus; Insulin; Insulin Resistance; Male; Memory; Mice; Myrtaceae; Obesity; Oxidative Stress; Phosphorylation; tau Proteins; Weight Gain

The peel of the native Brazilian fruit jaboticaba is rich in anthocyanins, which are known for their anti-obesity effects in animal models. The aim of the present study was to evaluate the effects of freeze-dried jaboticaba peel powder (FDJPP) on a number of metabolic parameters in a model of diet-induced obesity. Mice (n 8 per group) were initially fed on a high-fat diet (HFD, 35% w/w) for 4 weeks and then switched to a HFD supplemented with FDJPP (1, 2 or 4% w/w) for an additional 6 weeks. Energy intake, weight loss, glucose tolerance, insulin resistance and lipid profile were determined, and the results were evaluated using ANOVA and Tukey’s tests. The FDJPP exerted no protective effect on HFD-induced weight gain, hyperleptinaemia and glucose intolerance. However, the supplementation was effective to reduce insulin resistance, as evidenced in the insulin tolerance test, and subsequently confirmed by improved signal transduction through the insulin receptor/insulin receptor substrate-1/Akt/forkhead box protein pathway and by the attenuation of HFD-induced inflammation in the liver, verified by lower expressions of IL-1b and IL-6 and decreased phosphorylated IkB-a protein levels in all jaboticaba-treated mice. These results suggest that FDJPP may exert a protective role against obesity-associated insulin resistance.

Topics: Analysis of Variance; Animals; Anthocyanins; Anti-Obesity Agents; Diet, High-Fat; Dietary Supplements; Fruit; Glucose Intolerance; Inflammation; Insulin; Insulin Resistance; Leptin; Liver; Male; Mice; Mice, Inbred Strains; Myrtaceae; Obesity; Phytotherapy; Plant Preparations; Powders; Receptor, Insulin; Signal Transduction; Weight Gain

This study investigated the glucose uptake activity of the water extracts from the leaves and fruit of edible Myrtaceae plants, including guava (Psidium guajava Linn.), wax apples [Syzygium samarangense (Blume) Merr. and L.M. Perry], Pu-Tau [Syzygium jambo (L.) Alston], and Kan-Shi Pu-Tau (Syzygium cumini Linn.) in FL83B mouse hepatocytes. The fluorescent dye 2-(n-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose was used to estimate the uptake ability of the cells. Glucose uptake test showed that pink wax apple fruit extract (PWFE) exhibits the highest glucose uptake activity, at an increment of 21% in the insulin-resistant FL83B mouse hepatocytes as compared with the TNF-α-treated control group. Vescalagin was isolated using column chromatography of PWFE. This compound, at the concentration of 6.25 µg/mL, exhibits the same glucose uptake improvement in insulin-resistant cells as PWFE at a 100-µg/mL dose. We postulate that vescalagin is an active component in PWFE that may alleviate the insulin resistance in mouse hepatocytes.

Topics: 4-Chloro-7-nitrobenzofurazan; Animals; Cell Line; Deoxyglucose; Fruit; Glucose; Hepatocytes; Hydrolyzable Tannins; Hypoglycemic Agents; Insulin Resistance; Mice; Myrtaceae; Plant Extracts; Plant Leaves; Plants, Edible; Tumor Necrosis Factor-alpha

Inflammation is associated with the development of insulin resistance in Type 2 diabetes mellitus. In the present study, mouse FL83B cells were treated with tumor necrosis factor-alpha (TNF-α) to induce insulin resistance, and then co-incubated with a fraction from wax apple fruit extract (FWFE). This fraction significantly increased the uptake of the nonradioactive fluorescent indicator 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) in insulin resistant cells. Western blot analysis revealed that, compared with the TNF-α-treated control group, FWFE increased the expression of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), protein kinase B (Akt/PKB), phosphatidylinositol-3 kinase (PI3K), and glucose transporter 2 (GLUT-2), and increased IR tyrosyl phosporylation, in insulin resistant FL83B cells. However, FWFE decreased phosphorylation of c-Jun N-terminal kinases (JNK), but not the expression of the intercellular signal-regulated kinases (ERK), in the same cells. These results suggest that FWFE might alleviate insulin resistance in TNF-α-treated FL83B cells by activating PI3K-Akt/PKB signaling and inhibiting inflammatory response via suppression of JNK, rather than ERK, activation.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Drug Evaluation, Preclinical; Fruit; Glucose; Glucose Transporter Type 2; Hepatocytes; Insulin; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Mice; Myrtaceae; Phosphatidylinositol 3-Kinases; Plant Extracts; Proto-Oncogene Proteins c-akt; Receptor, Insulin; Signal Transduction; Tumor Necrosis Factor-alpha