Nil-Surin Rice Bran Hydrolysates Improve Lipid Metabolism and Hepatic Steatosis by Regulating Secretion of Adipokines and Expression of Lipid-Metabolism Genes.

Overconsumption of a high caloric diet is associated with metabolic disorders and a heightened risk of diabetes mellitus (DM), hepatic steatosis, and cardiovascular complications. The use of functional food has received much attention as a strategy in the prevention and treatment of metabolic disorders. This present study investigated whether Nil-Surin rice bran hydrolysates (NRH) could prevent or ameliorate the progression of metabolic disorders in rats in which insulin resistance (IR) was induced by a high fat-high fructose diet (HFFD). After 10 weeks of the HFFD, the rats showed elevated fasting blood glucose (FBG), impaired glucose tolerance, dysregulation of adipokine secretion, distorted lipid metabolism such as dyslipidemia, and increased intrahepatic fat accumulation. The IR was significantly attenuated by a daily dose of NRH (100 or 300 mg/kg/day). Doses of NRH rectified adipokine dysregulation by increasing serum adiponectin and improving hyperleptinemia. Interestingly, NRH decreased intrahepatic fat accumulation and improved dyslipidemia as shown by decreased levels of hepatic triglyceride (TG) and serum TG, total cholesterol and low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol. In addition, a modulation of expression of lipid metabolism genes was observed: NRH prevented upregulation of the lipogenesis genes Srebf1 and Fasn. In addition, NRH enhanced the expression of fatty-acid oxidation genes, as evidenced by an increase of Ppara and Cpt1a when compared with the HFFD control group. The activities of NRH in the modulation of lipid metabolism and rectifying the dysregulation of adipokines may result in a decreased risk of DM and hepatic steatosis. Therefore, NRH may be beneficial in ameliorating metabolic disorders in the HFFD model.

Antihypertensive effect of Mali-Nil surin rice bran hydrolysate and its mechanisms related to the EDHF-mediated vasorelaxation and L-type Ca2+ channel-mediated vasoconstriction in L-NAME hypertensive rats.

Mali-Nil Surin rice bran hydrolysate (MRH) contains highly nutritional proteins and beneficial phenolic compounds. This study investigated an antihypertensive effect of MRH and evaluated the mechanisms mediating this action in Nω-nitro-L-arginine-methyl ester (L-NAME)-induced hypertensive rats. Antihypertensive activity was determined in male rats orally administered with MRH (100 or 300 mg/kg) or enalapril (15 mg/kg) daily together with L-NAME (50 mg/kg/day) in drinking water, for 21 days. Concurrent oral treatment with MRH lowered the high blood pressure in the L-NAME-induced hypertensive rats. MRH treatment improved endothelial function and increased the endothelium-derived hyperpolarizing factor-mediated vasorelaxation in L-NAME hypertensive rats. L-NAME rats treated with MRH had reduced adrenergic hypercontractility, which was associated with a decrease in L-type calcium channel-mediated vasoconstriction. In addition, MRH exhibited antioxidant activity in hypertensive rats, as indicated by suppression of vascular superoxide anion production and reduction of malondialdehyde levels, as well as magnification of superoxide dismutase and catalase activities in serum. This study demonstrated the nutraceutical potential of MRH to prevent oxidative stress-related vascular dysfunction in hypertension.

Pluchea indica Leaf Extract Alleviates Dyslipidemia and Hepatic Steatosis by Modifying the Expression of Lipid Metabolism-Related Genes in Rats Fed a High Fat-High Fructose Diet.

This study evaluated the effect of Pluchea indica leaf extract (PIE) on dyslipidemia and lipid accumulation in the liver, emphasizing its molecular mechanisms in regulating lipid metabolism in rats fed a high fat-high fructose diet (HFFD). Male rats were fed HFFD (40% lard and 20% fructose) for ten weeks. They were then divided into four groups receiving distilled water, PIE (100 or 300 mg/kg/d), and pioglitazone (10 mg/kg/d) for a further six weeks, during which the HFFD was continued. After the experiment, fasting blood glucose (FBG), oral glucose tolerance (OGT), serum insulin and leptin levels, lipid profiles, and hepatic triglyceride content were measured. Histological examination and expression levels of lipid metabolism-related genes in the liver were measured. HFFD-fed rats indicated a significantly increased FBG, serum leptin, and homeostasis model assessment of insulin resistance (HOMA-IR) scores with impaired OGT and dyslipidemia compared to rats fed a normal diet. PIE significantly reduced FBG, serum leptin, and HOMA-IR scores and improved OGT. Additionally, PIE significantly improved dyslipidemia and decreased serum-free fatty acids and liver triglyceride content. Hepatic histological examination showed a marked reduction lipid accumulation in relation to HFFD controls. Interestingly, PIE significantly downregulated the expression of lipid synthesis-related genes and upregulated the expression of fatty-acid oxidation-related genes. In conclusion, PIE alleviates dyslipidemia and hepatic steatosis in HFFD rats plausibly by increasing insulin resistance and modifying the gene expression associated with lipid metabolism. PIE may be used as preventive nutrition for dyslipidemia and hepatic steatosis.

Effect of Thunbergia laurifolia water extracts on hepatic insulin resistance in high-fat diet-induced obese mice

Objective: To examine the effect of water extract of Thunbergia laurifolia on hepatic insulin resistance in high-fat diet-induced obese mice. Methods: High-fat diet with 45 kcal％ lard fat was used for obesity induction in ICR mice. The mice were fed with high-fat diet for 16 weeks, and during the last 8 weeks, they were treated with 200 mg/kg/day of water extracts from Thunbergia laurifolia leaf, stem and flower. Serum biochemistry, liver histology, and protein expression were examined after the treatment. Results: Extracts from all of the three parts of Thunbergia laurifolia significantly alleviated hyperglycemia, hyperlipidemia, hyperinsulinemia, and hyperleptinemia. The stem and flower extracts improved glucose tolerance. All of the extracts significantly reduced serum TNFα and monocyte chemoattractant protein-1 levels. Liver weight, triglyceride levels, and lipid accumulation were also decreased. Moreover, hepatic glucose-6-phosphatase level was significantly decreased, while the levels of PPARα, phosphorylated AMPK, and phosphorylated Akt were significantly increased with treatment of Thunbergia laurifolia extracts. Conclusions: Thunbergia laurifolia extracts can ameliorate hepatic insulin resistance in high-fat diet-induced obese mice by improving glucose and lipid homeostasis, which may be associated with stimulating phosphorylation of AMPK and Akt pathways.

Moringa oleifera leaf extract enhances endothelial nitric oxide production leading to relaxation of resistance artery and lowering of arterial blood pressure.

A mass of evidence has identified a promoting of nitric oxide (NO) production in endothelial cells using natural products as a potential strategy to prevent and treat hypertension. This study investigated whether the aqueous extract of Moringa oleifera leaves (MOE) could lower mean arterial pressure (MAP) and relax mesenteric arterial beds in rats via stimulating endothelium-derived NO production. Intravenous administration of MOE (1-30 mg/kg) caused a dose-dependent reduction in MAP in anesthetized rats. In rats pretreated with the NO-synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg, i.v.), the effect of MOE on MAP was significantly reduced. MOE (0.001-3 mg) induced relaxation in methoxamine (10 µM) pre-contracted mesenteric arterial beds, which was abolished by endothelium denudation. This endothelium-dependent vasorelaxation was reduced by L-NAME (100 µM) or the NO-sensitive guanylyl cyclase inhibitor, 1H- [1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (10 µM). In primary human pulmonary artery endothelial cells, MOE (3-30 µg/mL) induced NO production, which was inhibited by L-NAME (100 µM) pretreatment. These findings show that MOE stimulates the endothelium-derived NO release for driving its vasorelaxation to lower arterial blood pressure. These suggest the development of MOE as a natural antihypertensive supplement.

Moringa oleifera leaf extract induces vasorelaxation via endothelium-dependent hyperpolarization and calcium channel blockade in mesenteric arterial beds isolated from L-NAME hypertensive rats.

BACKGROUND: An aqueous extract of Moringa oleifera leaves (MOE) is known to cause relaxation of mesenteric resistance arteries of rats in which hypertension has been induced by the administration of L-NAME, but the mechanism(s) of action of MOE remains unclear. The purpose of this study was to investigate these mechanisms in mesenteric arterial beds isolated from L-NAME induced hypertensive rats. Methods: An investigation of vascular reactivity was conducted on isolated mesenteric arterial beds by measuring the changes in perfusion pressure using an in vitro system. RESULTS: MOE (0.001-3 mg in 0.1 ml injection volume) caused a dose-dependent relaxation in methoxamine (5 µM) pre-contracted arterial beds, which was partially abolished by endothelium removal. The endothelium-dependent component of vasorelaxation was insensitive to both L-NAME (100 µM) and indomethacin (10 µM), while completely inhibited in high KCl (45 mM)-induced contraction. MOE (1 and 3 mg/ml) showed a dose-dependent inhibitory effect on CaCl2-induced contractions of denuded preparations in Ca2+-free medium containing a high KCl (60 mM) or methoxamine (10 µM). In Ca2+-free medium, MOE (3 mg/ml) also inhibited phenylephrine-induced contractions of denuded preparations. Conclusion: These findings suggest that MOE relaxes mesenteric arterial beds of L-NAME hypertensive rats via both endothelium-dependent and endothelium-independent mechanisms. The endothelium-dependent action occurred via endothelium-derived hyperpolarizing factor-mediated hyperpolarization. The endothelium-independent action was related to blocking the entry of extracellular Ca2+ via voltage-operated and receptor-operated Ca2+ channels, and inhibiting mobilization of sarcolemmal Ca2+ via inositol trisphosphate receptor Ca2+ channels. MOE may be potentially useful as a natural vasodilator against hypertension.

Hydrogen sulfide as a mediator of endothelium-dependent relaxation evoked by Moringa oleifera leaf extract in mesenteric arterial beds isolated from L-NAME hypertensive rats.

OBJECTIVES: Aqueous extract of Moringa oleifera leaves (MOE) is a potent inducer of endothelium-dependent relaxation of mesenteric resistance arteries of rats induced to be hypertensive using Nω-nitro-L-arginine methyl ester (L-NAME). Hydrogen sulfide (H2S) has been shown to participate in endothelium-dependent relaxation of small resistance arteries. Therefore, this study aimed to investigate whether endothelial H2S-dependent signaling plays a role in the vasorelaxation in response to MOE. METHODS: Mesenteric arterial beds isolated from L-NAME hypertensive rats were set up in an ex vivo perfusion system for measurement of vasoreactivity. All experiments were performed in the presence of the nitric oxide synthase inhibitor, L-NAME (100 µM) and the cyclooxygenase inhibitor, indomethacin (10 µM) to prevent the formation of nitric oxide and prostanoids, respectively. RESULTS: In the presence of the nitric oxide synthase inhibitor, L-NAME and the cyclooxygenase inhibitor, indomethacin, the endothelium-dependent vasorelaxation induced by MOE (0.001-3 mg) was completely inhibited by DL-propargylglycine (100 µM), which inhibits the H2Sgenerating enzyme, cystathionine γ-lyase. This H2Sdependent response was reduced by the KATP channel blocker; glibenclamide (10 µM), the KCa channel blocker; tetraethylammonium (1 µM), and the myo-endothelial gap-junctional uncoupler; 18α-glycyrrhetinic acid (10 µM). In contrast, the muscarinic receptor antagonist, atropine (100 µM), did not affect the response to MOE. CONCLUSIONS: The results may suggest that H2S is the likely mediator of endothelium-dependent relaxation in response to MOE in mesenteric arterial beds of L-NAME-induced hypertensive rats. MOE-induced H2S-dependent vasorelaxation involves activation of KATP and KCa channels and requires myo-endothelial gap-junctional communication.

Opisthorchis viverrini Infection Augments the Severity of Nonalcoholic Fatty Liver Disease in High-Fat/High-Fructose Diet-Fed Hamsters.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, including in regions where helminth infections such as the fish-borne liver fluke Opisthorchis viverrini (Ov) also occur. We investigated the effects of a high-fat and high-fructose (HFF) diet on the development and progression of NAFLD in experimental opisthorchiasis. Two groups of hamsters were infected with Ov for 4 months before the experiment to induce chronic inflammation. One of these groups (OvHFF) was fed with a HFF diet for up to further 4 months. One uninfected group of hamsters served as the normal control group, and another received the HFF diet (HFF group) for up to 4 months. Histopathology, biochemical parameters, and ultrastructural features of liver were investigated. In a short-term treatment, the OvHFF group showed significantly better homeostatic model assessment for insulin resistance level and lower liver lipid than did the HFF group. By contrast, histopathological characteristics of severe NAFLD were prominent in the OvHFF group after 4 months on the HFF diet, findings which were supported by confirmatory ultrastructural changes. In conclusion, opisthorchiasis induced the severe NAFLD in hamsters fed high-fat/high-fructose diets.

Moringa oleifera leaf extract lowers high blood pressure by alleviating vascular dysfunction and decreasing oxidative stress in L-NAME hypertensive rats.

BACKGROUND: Enhancing relaxation of resistance arteries and decreasing oxidative stress by using natural products are potential strategies for prevention and treatment of hypertension. PURPOSE: This study investigated whether aqueous extract of Moringa oleifera leaves (MOE) could alleviate Nω-nitro-L-arginine-methyl ester (L-NAME)-induced high blood pressure via modulation of vascular function and antioxidant properties. METHODS: An experimental hypertensive model was established by administration of L-NAME (50 mg/kg/day) in drinking water to male Wistar rats for 3 weeks. Arterial pressure was measured indirectly by tail-cuff plethysmography and directly via femoral artery catheterization. Vasoreactivity of isolated rat mesenteric arterial bed was determined by the changes in perfusion pressure detected by a pressure transducer. Vascular superoxide anion (O2•-) production was determined by lucigenin-enhanced chemiluminescence. Other biochemical measurements including malondialdehyde (MDA) level, superoxide dismutase (SOD), and catalase (CAT) activities were measured by colorimetric assay. RESULTS: L-NAME-treated rats developed significantly increased blood pressure and heart rate. Concurrent oral treatment with MOE (30 and 60 mg/kg/day) could decrease the high blood pressure and tachycardia in a dose-dependent manner. MOE reduced the impairment of acetylcholine-induced relaxation and decreased the hyperreactivity of adrenergic-mediated contraction in response to periarterial nerve stimulation and phenylephrine in isolated mesenteric arterial beds. In addition, MOE exhibited antioxidant effects in the hypertensive rats, as indicated by suppression of vascular O2•- production, decrease of plasma and thoracic aorta MDA levels, and increase of antioxidant activities of SOD and CAT. Moreover, MOE (0.001-0.3 mg) produced a dose-dependent relaxation in methoxamine pre-contracted arterial beds isolated from L-NAME hypertensive rats, which was abolished by endothelium denudation. CONCLUSION: These findings suggest that the antihypertensive effect of MOE in L-NAME-hypertensive rats may be mediated by alleviating vascular dysfunction and oxidative stress and promoting endothelium-dependent vasorelaxation. MOE may be potentially useful as a natural product against hypertension.

Vernonia cinerea water extract improves insulin resistance in high-fat diet-induced obese mice.

Vernonia cinerea (V cinerea) is a plant distributed in grassy areas in Southeast Asia and has several pharmacological effects, including antidiabetic activity. However, the information available regarding the effect of V cinerea on insulin resistance in high-fat diet (HFD)-induced obese mice is not yet determined. We hypothesized that V cinerea water extract (VC) improves insulin sensitivity in HFD-induced obese mice by modulating both phosphatidylinositol-3-kinase (PI3K) and adenosine monophosphate-activated protein kinase (AMPK) pathways in liver, skeletal muscle, and adipose tissue. Obesity was induced in mice from the Institute for Cancer Research by feeding an HFD 188.28 kJ (45 kcal % lard fat) for 12 weeks. During the last 6 weeks of the HFD, obese mice were treated with VC (250 and 500 mg/kg). We found that VC at both doses significantly reduced the hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia. Obese mice treated with VC could increase serum adiponectin but reduce the proinflammatory cytokines, tumor necrosis factor-α, and monocyte chemoattractant protein-1. The extracts decreased triglyceride storage in liver and skeletal muscle of obese mice. The average size of fat cells was smaller in VC-treated groups than that of the HFD group. The protein expressions of PI3K and AMPK pathways in liver, skeletal muscle, and adipose tissue were upregulated (increased phosphorylation of PI3K, protein kinase B, AMPK, and acetyl-CoA carboxylase) by VC treatment. Furthermore, the glucose transporter 4 was increased in muscle and adipose tissue in obese mice treated with VC. These data indicate that VC treatment stimulates phosphorylation of PI3K and AMPK pathways in liver, muscle, and adipose tissue. Stimulating these pathways may improve impaired glucose and lipid homeostasis in an HFD-induced obesity mouse model. Based on these findings, it appears that VC has potential as a functional food or therapeutic agent in management of insulin resistance related diseases, such as type 2 diabetes mellitus.

Co-occurrence of opisthorchiasis and diabetes exacerbates morbidity of the hepatobiliary tract disease.

Complications arising from infection with the carcinogenic liver fluke Opisthorchis viverrini cause substantial morbidity and mortality in Thailand and adjacent lower Mekong countries. In parallel, the incidence rate of diabetes mellitus (DM) is increasing in this same region, and indeed worldwide. Many residents in opisthorchiasis-endemic regions also exhibit DM, but the hepatobiliary disease arising during the co-occurrence of these two conditions remains to be characterized. Here, the histopathological profile during co-occurrence of opisthorchiasis and DM was investigated in a rodent model of human opisthorchiasis in which diabetes was induced with streptozotocin. The effects of excretory/secretory products from the liver fluke, O. viverrini (OVES) on hepatocyte and cholangiocyte responses during hyperglycemic conditions also were monitored. Both the liver fluke-infected hamsters (OV group) and hamsters with DM lost weight compared to control hamsters. Weight loss was even more marked in the hamsters with both opisthorchiasis and DM (OD group). Hypertrophy of hepatocytes, altered biliary canaliculi, and biliary hyperplasia were more prominent in the OD group, compared with OV and DM groups. Profound oxidative DNA damage, evidenced by 8-oxo-2'-deoxyguanosine, proliferating cell nuclear antigen, and periductal fibrosis characterized the OD compared to OV and DM hamsters. Upregulation of expression of cytokines in response to infection and impairment of the pathway for insulin receptor substrate (IRS)/phosphatidylinositol-3-kinases (PI3K)/protein kinase B (AKT) signaling attended these changes. In vitro, OVES and glucose provoked time- and dose-dependent effects on the proliferation of both hepatocytes and cholangiocytes. In overview, the co-occurrence of opisthorchiasis and diabetes exacerbated pathophysiological damage to the hepatobiliary tract. We speculate that opisthorchiasis and diabetes together aggravate hepatobiliary pathogenesis through an IRS/PI3K/AKT-independent pathway.

Rice bran protein hydrolysates reduce arterial stiffening, vascular remodeling and oxidative stress in rats fed a high-carbohydrate and high-fat diet.

PURPOSE: Rice bran protein hydrolysates (RBPH) contain highly nutritional proteins and antioxidant compounds which show benefits against metabolic syndrome (MetS). Increased arterial stiffness and the components of MetS have been shown to be associated with an increased risk of cardiovascular disease. This study aimed to investigate whether RBPH could alleviate the metabolic disorders, arterial stiffening, vascular remodeling, and oxidative stress in rats fed a high-carbohydrate and high-fat (HCHF) diet. METHODS: Male Sprague-Dawley rats were fed either a standard chow and tap water or a HCHF diet and 15 % fructose solution for 16 weeks. HCHF rats were treated orally with RBPH (250 or 500 mg/kg/day) for the final 6 weeks of the experimental period. RESULTS: Rats fed with HCHF diet had hyperglycemia, insulin resistance, dyslipidemia, hypertension, increased aortic pulse wave velocity, aortic wall hypertrophy and vascular remodeling with increased MMP-2 and MMP-9 expression. RBPH supplementation significantly alleviated these alterations (P < 0.05). Moreover, RBPH reduced the levels of angiotensin-converting enzyme (ACE) and tumor necrosis factor-alpha in plasma. Oxidative stress was also alleviated after RBPH treatment by decreasing plasma malondialdehyde, reducing superoxide production and suppressing p47phox NADPH oxidase expression in the vascular tissues of HCHF rats. RBPH increased plasma nitrate/nitrite level and up-regulated eNOS expression in the aortas of HCHF-diet-fed rats, indicating that RBPH increased NO production. CONCLUSION: RBPH mitigate the deleterious effects of HCHF through potential mechanisms involving enhanced NO bioavailability, anti-ACE, anti-inflammatory and antioxidant properties. RBPH could be used as dietary supplements to minimize oxidative stress and vascular alterations triggered by MetS.

Rice bran protein hydrolysates attenuate diabetic nephropathy in diabetic animal model.

INTRODUCTION: Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells. METHODS: Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks. At the end of the experiment, diabetic nephropathy in kidney tissues was investigated for histological, ultrastructural, and clinical chemistry changes, and biomarkers of angiogenesis, fibrosis, inflammation, and antioxidant in kidney were analyzed by Western blotting. Protection against proangiogenic proteins and induction of cytoprotection by RBP in cultured mesangial cells was evaluated. RESULTS: RBP treatment improved insulin sensitivity, decreased elevated fasting serum glucose levels, and improved serum lipid levels and urinary albumin/creatinine ratios in diabetic mice. RBP ameliorated the decreases in podocyte slit pore numbers, thickening of glomerular basement membranes, and mesangial matrix expansion and suppressed elevation of MCP-1, ICAM-1, HIF-1α, VEGF, TGF-ß, p-Smad2/3, and type IV collagen expression. Moreover, RBP restored suppressed antioxidant Nrf2 and HO-1 expression. In cultured mesangial cells, RBP inhibited high glucose-induced angiogenic protein expression and induced the expression of Nrf2 and HO-1. CONCLUSION: RBP attenuates the progression of diabetic nephropathy and restored renal function by suppressing the expression of proangiogenic and profibrotic proteins, inhibiting proinflammatory mediators, and restoring the antioxidant and cytoprotective system.

Anti-insulin resistant effect of ferulic acid on high fat diet-induced obese mice

To evaluate the insulin sensitivity action of ferulic acid (FA) in skeletal muscle and hypothalamus of high-fat diet (HFD)-induced obese mice.Methods: Obese mouse model was induced by HFD (45 kcal％ lard fat) for 16 weeks. After 8 weeks of HFD feeding, these obese mice were orally treated with FA at doses of 25 and 50 mg/kg/day for 8 weeks. At the end of all treatments, the epididymal fat, pancreas, skeletal muscle and hypothalamus were removed for biochemical parameter and protein expression examinations.Results: FA treatment significantly decreased leptin level in fat tissue and insulin level in pancreas (P < 0.05). Interestingly, obese mice treated with FA increased the protein expressions of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and phosphorylated-protein kinase B in both muscle and brain (P < 0.05). The phosphorylations of adenosine monophosphate-activated protein kinase and acetyl-CoA carboxylase in muscle, and leptin receptor protein in hypothalamus were also increased (P < 0.05). The pancreatic islets histology showed smaller size in obese mice treated with FA compared to untreated obese mice.Conclusions: These findings indicate the beneficial effect of FA in improving insulin resistance in HFD-induced obese mice. These effects are probably mediatedvia modulating the insulin receptor substrate/phosphatidylinositol 3-kinase/protein kinase B or adenosine monophosphate-activated protein kinase pathways.

Garcinia mangostana pericarp extract protects against oxidative stress and cardiovascular remodeling via suppression of p47phox and iNOS in nitric oxide deficient rats.

Nω-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension and cardiovascular remodeling are associated with oxidative stress and inflammation. Garcinia mangostana Linn., has been reported to have antioxidant and anti-inflammatory properties. This study investigated whether G. mangostana pericarp extract (GME) could prevent l-NAME-induced hemodynamic alterations, cardiovascular remodeling, oxidative stress and inflammation in rats. Male Sprague-Dawley rats were given 40mg/kg/day of l-NAME in drinking water to induce hypertension, and were simultaneously treated with GME at a dose of 200mg/kg/day. Rats that received l-NAME for five weeks had high blood pressure, left ventricular hypertrophy and thickening of aortic wall. Vascular superoxide production, plasma malondialdehyde (MDA), and plasma tumor necrosis factor alpha (TNF-α) were significantly increased in l-NAME-hypertensive rats (p<0.05). This was consistent with up-regulation of the p47phox NADPH oxidase subunit and iNOS protein expression in aortic tissues (p<0.05). Low levels of plasma nitric oxide metabolites were observed in l-NAME hypertension. GME prevented the development of hypertension and cardiovascular remodeling induced by l-NAME with reduced oxidative stress and inflammation. These data suggest that GME had a protective effect against l-NAME-induced hypertension and cardiovascular remodeling via suppressing p47phox NADPH oxidase subunit and iNOS protein expression resulting in enhancing NO bioavailability.

Morin attenuates hepatic insulin resistance in high-fat-diet-induced obese mice

Morin is a natural bioflavonoid that exhibits antioxidant and anti-inflammatory properties. The present study was designed to evaluate the effect of morin on insulin resistance, oxidative stress, and inflammation in a high-fat-diet (HFD)-induced obese mice. Obesity was induced in ICR mice by feeding a HFD (60 % kcal from fat) for 12 weeks. After the first 6 weeks, obese mice were treated with morin (50 or 100 mg/kg/day) once daily for further 6 weeks. Blood glucose, lipid profile, insulin, leptin, adiponectin, and markers of oxidative stress and inflammation were then measured. Liver was excised, subjected to histopathology, glycogen determination, and gene and protein expression analysis. Morin administration reduced blood glucose, serum insulin, leptin, malondialdehyde, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) levels and increased serum adiponectin levels. Moreover, there was a reduction in serum lipid and liver triglyceride levels. Liver histology indicated that morin limited accumulation of lipid droplets. Interestingly, morin reduced expression of hepatic sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and up-regulated hepatic carnitine palmitoyltransferase 1a (CPT1a) expression. Morin also stimulated glycogen storage and suppressed phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) protein expression. Furthermore, hepatic superoxide dismutase (SOD) and catalase (CAT) expression were increased after morin treatment. These findings indicate that morin has a positive effect in the HFD-induced obesity condition by suppressing lipogenesis, gluconeogenesis, inflammation, and oxidative stress activities (AU)

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Morin attenuates hepatic insulin resistance in high-fat-diet-induced obese mice.

Morin is a natural bioflavonoid that exhibits antioxidant and anti-inflammatory properties. The present study was designed to evaluate the effect of morin on insulin resistance, oxidative stress, and inflammation in a high-fat-diet (HFD)-induced obese mice. Obesity was induced in ICR mice by feeding a HFD (60 % kcal from fat) for 12 weeks. After the first 6 weeks, obese mice were treated with morin (50 or 100 mg/kg/day) once daily for further 6 weeks. Blood glucose, lipid profile, insulin, leptin, adiponectin, and markers of oxidative stress and inflammation were then measured. Liver was excised, subjected to histopathology, glycogen determination, and gene and protein expression analysis. Morin administration reduced blood glucose, serum insulin, leptin, malondialdehyde, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) levels and increased serum adiponectin levels. Moreover, there was a reduction in serum lipid and liver triglyceride levels. Liver histology indicated that morin limited accumulation of lipid droplets. Interestingly, morin reduced expression of hepatic sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and up-regulated hepatic carnitine palmitoyltransferase 1a (CPT1a) expression. Morin also stimulated glycogen storage and suppressed phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) protein expression. Furthermore, hepatic superoxide dismutase (SOD) and catalase (CAT) expression were increased after morin treatment. These findings indicate that morin has a positive effect in the HFD-induced obesity condition by suppressing lipogenesis, gluconeogenesis, inflammation, and oxidative stress activities.

Protocatechuic Acid Restores Vascular Responses in Rats With Chronic Diabetes Induced by Streptozotocin.

Oxidative stress has been shown to play an important role in development of vascular dysfunction in diabetes. Protocatechuic acid (PCA) has been reported to exert antioxidant and anti-hyperglycemic activities. Diabetes was induced in male Sprague-Dawley rats by a single intraperitoneal injection of 50 mg/kg streptozotocin (STZ). The rats were maintained in a state of hyperglycemia for 12 weeks. Then, PCA (50 or 100 mg/kg/day) was administered orally or insulin (4 U/kg/day) was subcutaneous injected to the rats for 6 weeks. Blood pressure, vascular responses to vasoactive agents, vascular superoxide production, blood glucose, insulin, malondialdehyde, nitric oxide and antioxidant enzymes were examined. The diabetic rats showed weight loss, insulin deficiency, hyperglycemia, increased oxidative stress, decreased plasma nitric oxide, elevated blood pressure, increased vascular response to phenylephrine and decreased vascular responses to acetylcholine and sodium nitroprusside. PCA significantly decreased blood glucose and oxidative stress, and increased plasma nitric oxide in diabetic rats. Interestingly, PCA treatment restored blood pressure and vascular reactivity, and antioxidant enzyme activity diabetic rats. This study provides the first evidence of the efficacy of PCA in restoring the vascular reactivity of diabetic rats. The mechanism of action may be associated with an alleviation of oxidative stress.

Ferulic acid improves lipid and glucose homeostasis in high-fat diet-induced obese mice.

Ferulic acid (FA) is a plant phenolic acid that has several pharmacological effects including antihyperglycaemic activity. Thus, the objective of this study is to investigate the effect of FA on glucose and lipid metabolism in high-fat diet (HFD)-induced obese mice. Institute for Cancer Research (ICR) mice were fed a HFD (45 kcal% fat) for 16 weeks. At the ninth week of induction, the obese mice were orally administered with daily FA doses of 25 and 50 mg/kg for the next eight weeks. The results show that FA significantly reduced the elevated blood glucose and serum leptin levels, lowered the insulin resistance, and increased the serum adiponectin level. Moreover, serum lipid level, and liver cholesterol and triglyceride accumulations were also reduced. The histological examination showed clear evidence of a decrease in the lipid droplets in liver tissues and smaller size of fat cells in the adipose tissue in the obese mice treated with FA. Interestingly, FA reduced the expression of hepatic lipogenic genes such as sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). It could also up-regulate hepatic carnitine palmitoyltransferase 1a (CPT1a) gene and peroxisome proliferator-activated receptor alpha (PPARα) proteins. The FA treatment was also found to suppress the protein expressions of hepatic gluconeogenic enzymes, phosphoenolpyruvate carboxylase (PEPCK) and glucose-6-phosphatase (G6Pase). In conclusion, the findings of this study demonstrate that FA improves the glucose and lipid homeostasis in HFD-induced obese mice probably via modulating the expression of lipogenic and gluconeogenic genes in liver tissues.

Rice Bran Protein Hydrolysates Improve Insulin Resistance and Decrease Pro-inflammatory Cytokine Gene Expression in Rats Fed a High Carbohydrate-High Fat Diet.

A high carbohydrate-high fat (HCHF) diet causes insulin resistance (IR) and metabolic syndrome (MS). Rice bran has been demonstrated to have anti-dyslipidemic and anti-atherogenic properties in an obese mouse model. In the present study, we investigated the beneficial effects of rice bran protein hydrolysates (RBP) in HCHF-induced MS rats. After 12 weeks on this diet, the HCHF-fed group was divided into four subgroups, which were orally administered RBP 100 or 500 mg/kg, pioglitazone 10 mg/kg, or tap water for a further 6 weeks. Compared with normal diet control group, the MS rats had elevated levels of blood glucose, lipid, insulin, and HOMA-IR. Treatment with RBP significantly alleviated all those changes and restored insulin sensitivity. Additionally, RBP treatment increased adiponectin and suppressed leptin levels. Expression of Ppar-γ mRNA in adipose tissues was significantly increased whereas expression of lipogenic genes Srebf1 and Fasn was significantly decreased. Levels of mRNA of proinflammatory cytokines, Il-6, Tnf-α, Nos-2 and Mcp-1 were significantly decreased. In conclusion, the present findings support the consumption of RBP as a functional food to improve insulin resistance and to prevent the development of metabolic syndrome.