ETHANOLIC EXTRACT OF TUBTIM-CHUMPHAE RICE BRAN DECREASES INSULIN RESISTANCE AND INTRAHEPATIC FAT ACCUMULATION IN HIGH-FAT-HIGH-FRUCTOSE DIET FED RATS

Objective: Tubtim-chumphae rice is hybrid Thai rice with a red pericarp. This study was aimed to investigate the effect of Tubtim-chumphae rice bran on insulin resistance and intrahepatic fat accumulation in high-fat-high-fructose diet (HFFD) fed rats.Methods: Ethanolic extract of rice bran (ERB) was prepared using a 50% ethanol-water. Male Sprague-Dawley rats were fed HFFD (40% lard, 20% fructose) for 10 weeks, followed by concomitant administrations of distilled water or ERB at 250 or 500 mg/kg/day or pioglitazone at 10 mg/kg/day for a further 4 weeks in treated groups. Normal control rats were fed normal chow and distilled water. At the end of all treatments, fasting blood glucose (FBG), an oral glucose tolerance test (OGTT), serum insulin levels, lipid profiles, and liver fat contents were measured. Liver histological and peroxisome proliferator-activated receptor-α (PPAR-α) gene expression examinations were performed.Results: At week 14, control HFFD rats had significantly (p<0.05) higher FBG, low-density lipoprotein cholesterol, triglycerides, and insulin secretions together with impaired OGTT as compared to normal control rats. These parameters indicated an insulin resistant and dyslipidemic condition in HFFD rats. ERB 250 and 500 mg/kg or pioglitazone 10 mg/kg significantly ameliorated all of these changes. HFFD also caused a significant increase in fat accumulation and a decrease in PPAR-α gene expression in the livers which were significantly decreased by ERB.Conclusions: ERB decreases insulin resistance and intrahepatic fat accumulation possibly through increasing PPAR-α gene expression in HFFD rats. ERB might possibly be a neutraceutical for the metabolic syndrome patients.1. Gauthier MS, Favier R, Lavoie JM. Time course of the development of non-alcoholic hepatic steatosis in response to high-fat diet-induced obesity in rats. Br J Nutr 2006;95:273-81.2. Roberts CK, Hevener AL, Barnard RJ. Metabolic syndrome and insulin resistance: Underlying causes and modification by exercise training. Compr Physiol 2013;3:1-58.3. Grundy SM. Metabolic syndrome update. Trends Cardiovasc Med 2016;26:364-73.4. Fouret G, Gaillet S, Lecomte J, Bonafos B, Djohan F, Barea B, et al. 20-week follow-up of hepatic steatosis installation and liver mitochondrial structure and activity and their interrelation in rats fed a high-fat-high-fructose diet. Br J Nutr 2018;119:368-80.5. Dekker MJ, Su Q, Baker C, Rutledge AC, Adeli K. Fructose: A highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome. Am J Physiol Endocrinol Metab 2010;299:E685-94.6. Vichit W, Saewan N. Antioxidant activities and cytotoxicity of thai pigmented rice. Int J Pharm Pharm Sci 2015;7:329-34.7. Settharaksa S, Madaka F, Charkree K, Charoenchai L. The study of anti-inflammatory and antioxidant activity in cold press rice bran oil from rice in Thailand. Int J Pharm Pharm Sci 2014;6:428-31.8. Sukrasno S, Tuty S, Fidrianny I. Antioxidant evaluation and phytochemical content of various rice bran extracts of three varieties rice from Semarang, central Java, Indonesia. Asian J Pharm Clin Res 2017;10:377-82.9. Sabir A, Rafi M, Darusman LK. Discrimination of red and white rice bran from indonesia using HPLC fingerprint analysis combined with chemometrics. Food Chem 2017;221:1717-22.10. Niu Y, Gao B, Slavin M, Zhang X, Yang F, Bao J, et al. Phytochemical compositions, and antioxidant and anti-inflammatory properties of twenty-two red rice samples grown in Zhejiang. LWT Food Sci Technol 2013;54:521-7.11. Boonloh K, Kukongviriyapan V, Kongyingyoes B, Kukongviriyapan U, Thawornchinsombut S, Pannangpetch P, et al. Rice bran protein hydrolysates improve insulin resistance and decrease pro-inflammatory cytokine gene expression in rats fed a high carbohydrate-high fat diet. Nutrients 2015;7:6313-29.12. Peñarrieta JM, Alvarado JA, Akesson B, Bergenståhl B. Total antioxidant capacity and content of flavonoids and other phenolic compounds in canihua (Chenopodium pallidicaule): An andean pseudocereal. Mol Nutr Food Res 2008;52:708-17.13. Mungkhunthod S, Senggunprai L, Tangsucharit P, Sripui J, Kukongviriyapan U, Pannangpetch P. Antidesma thwaitesianum pomace extract improves insulin sensitivity via upregulation of PPAR-γ in high fat diet/streptozotocin-induced Type 2 diabetic rats. Asia Pac J Sci Technol 2016;21:63-76.14. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC, et al. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9.15. Naowaboot J, Wannasiri S. Anti-lipogenic effect of Senna alata leaf extract in high-fat diet-induced obese mice. Asian Pac J Trop Biomed 2016;6:232-8.16. Couturier K, Qin B, Batandier C, Awada M, Hininger-Favier I, Canini F, et al. Cinnamon increases liver glycogen in an animal model of insuli

Ferulic Acid Alleviates Changes in a Rat Model of Metabolic Syndrome Induced by High-Carbohydrate, High-Fat Diet

Agricultural Research Development Agency Fund, the Thailand Research Fund, the Khon Kaen University Research Fund and the Invitation Research Fund, Faculty of Medicine, Khon Kaen University. Senaphan K. was supported by a scholarship (PHD/0048/2553) from the Royal Golden Jubilee PhD Program, the Thailand Research Fun

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

Antihyperglycemic activity of agarwood leaf extracts in STZ-induced diabetic rats and glucose uptake enhancement activity in rat adipocytes

Agarwood leaf extract was found to possess antipyretic, laxative and antimicrobial activities. A trial of one diabeticpatient taking long term agarwood leaf tea was found to have blood glucose returned to normal. In this work, the effects ofmethanol, water and hexane crude extracts of agarwood leaf on hyperglycemia in streptozotocin-induced diabetic rats wereinvestigated. Only methanol and water extracts at the dose of 1 g/kg body weight lowered the fasting blood glucose levels,54 and 40%, respectively. The results were comparable to 4 U/kg body weight of insulin (73%). In in vitro experiment, theeffect of the methanol and water extracts at the concentration of 10 g/mL enhanced glucose uptake activity on ratadipocytes by 172±10 and 176±21% of the control, respectively. The glucose uptake enhancement activity is comparable to1.5 nM insulin (166±16%). The thin-layer chromatographic characteristics of all extracts were documented. The findingssuggest that agarwood leaf is a promising potential antidiabetic agent

Curcumin Protects against Cadmium-Induced Vascular Dysfunction, Hypertension and Tissue Cadmium Accumulation in Mice

Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd)—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L) in drinking water for eight weeks. Curcumin (50 or 100 mg/kg) was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd

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

Objective: 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 mediated via modulating the insulin receptor substrate/phosphatidylinositol 3-kinase/protein kinase B or adenosine monophosphate-activated protein kinase pathways

Peptides-Derived from Thai Rice Bran Improves Endothelial Function in 2K-1C Renovascular Hypertensive Rats

In recent years, a number of studies have investigated complementary medical approaches to the treatment of hypertension using dietary supplements. Rice bran protein hydrolysates extracted from rice is a rich source of bioactive peptides. The present study aimed to investigate the vasorelaxation and antihypertensive effects of peptides-derived from rice bran protein hydrolysates (RBP) in a rat model of two kidney-one clip (2K-1C) renovascular hypertension. 2K-1C hypertension was induced in male Sprague-Dawley rats by placing a silver clip around the left renal artery, whereas sham-operated rats were served as controls. 2K-1C and sham-operated rats were intragastrically administered with RBP (50 mg kg−1 or 100 mg kg−1) or distilled water continuously for six weeks. We observed that RBP augmented endothelium-dependent vasorelaxation in all animals. Administration of RBP to 2K-1C rats significantly reduced blood pressure and decreased peripheral vascular resistance compared to the sham operated controls (p &lt; 0.05). Restoration of normal endothelial function and blood pressure was associated with reduced plasma angiotensin converting enzyme (ACE), decreased superoxide formation, reduced plasma malondialdehyde and increased plasma nitrate/nitrite (p &lt; 0.05). Up-regulation of eNOS protein and down-regulation of p47phox protein were found in 2K-1C hypertensive rats-treated with RBP. Our results suggest that RBP possesses antihypertensive properties which are mainly due to the inhibition of ACE, and its vasodilatory and antioxidant activity

Mamao Pomace Extract Alleviates Hypertension and Oxidative Stress in Nitric Oxide Deficient Rats

Reactive oxygen species (ROS)-induced oxidative stress plays a major role in pathogenesis of hypertension. Antidesma thwaitesianum (local name: Mamao) is a tropical plant distributed in the tropical/subtropical areas of the world, including Thailand. Mamao pomace (MP), a by-product generated from Mamao fruits, contains large amounts of antioxidant polyphenolic compounds. The aim of this study was to investigate the antihypertensive and antioxidative effects of MP using hypertensive rats. For this purpose, male Sprague-Dawley rats were given Nω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of endothelial nitric oxide synthase (eNOS), in drinking water (50 mg/kg) for three weeks. MP extract was orally administered daily at doses of 100 and 300 mg/kg. l-NAME administration induced marked increase in blood pressure, peripheral vascular resistance, and oxidative stress. MP treatment significantly prevented the increase in blood pressure, hindlimb blood flow and hindlimb vascular resistance of l-NAME treated hypertensive rats (p &lt; 0.05). The antihypertensive effect of MP treatment was associated with suppression of superoxide production from carotid strips and also with an increase in eNOS protein expression and nitric oxide bioavailability. The present results provide evidence for the antihypertensive effect of MP and suggest that MP might be useful as a dietary supplement against hypertension