天然产物化学英文版副本汇总.doc
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1、Effect of Oryzanol and Ferulic Acid on the Glucose Metabolism of Mice Fed with a High-Fat DietMyoung Jin Son, Catherine W. Rico, Seok Hyun Nam, and Mi Young KangAbstract: The effects of oryzanol and ferulic acid on the glucose metabolism of high-fat-fed mice were investigated. Male C57BL/6N mice wer
2、e randomly divided into 4 groups: NC group fed with normal control diet; HF group fed with high-fat (17%) diet; HF-O group fed with high-fat diet supplemented with 0.5% oryzanol; and HF-FA group fed with high-fat diet supplemented with 0.5% ferulic acid. All animals were allowed free access to the e
3、xperimental diets and water for 7 wk. At the end of the experimental period, the HF-O and HF-FA groups exhibited significantly lower blood glucose level and glucose-6-phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities, and higher glycogen and insulin concentrations and glu
4、cokinase (GK) activity compared with NC and HF groups. The results of this study illustrate that both oryzanol and ferulic acid could reduce the risk of high-fat diet-induced hyperglycemia via regulation of insulin secretion and hepatic glucose-regulating enzyme activities.Keywords: diabetes, feruli
5、c acid, high-fat-fed mice, hypoglycemic effect, oryzanolIntroductionChronic consumption of a high-fat diet has been associated with the development of obesity and type 2 diabetes mellitus (Hill and others 1992; Bray and others 2004). Scientific studies have shown that excessive intake of dietary fat
6、 results in increased body weight and poor glucose regulation (Alsaif and Duwaihy2004; Petro and others 2004; Messier and others 2007). Diabetes is characterized by hyperglycemia that results in the generation of free radicals leading to oxidative stress (West 2000). Due to changes in lifestyle patt
7、erns, particularly poor eating habit and sedentary lifestyle, the incidence of diabetes has rapidly increased in epidemic proportions. Around 171 million cases of diabetes worldwide were reported in 2001 and it was projected that by 2030, 366 million people will have diabetes (Wild and others 2004).
8、 With this increasing global prevalence of diabetes, the need for therapeutic measures against the disease has become stronger and more urgent. A wide range of oral medicines are currently being used for treating diabetes. However, various adverse effects and high rates of secondary failures have be
9、en associated with the available antidiabetic medicines (Inzucchi 2002). Thus, finding natural drugs with hypoglycemic activity has now become the focus of scientists and researchers. At present, there is a considerable public and scientific interest in utilizing phytochemicals for the treatment and
10、 prevention of various diseases. Naturally occurring phenolic compounds, such as oryzanol and ferulic acid, are known to have strong antioxidant activities (Wang and others 2002; Srinivasan and others 2007). Oryzanol is a mixture of ferulic acid (4-hydroxy-3-methoxycinnamic acid) esters with phytost
11、erols (Lerma-Garcia and others 2009) and primarily extracted from rice bran. Ferulic acid is commonly found in fruits and vegetables, including banana, broccoli, rice bran, and citrus fruits (Zhao and Moghadasian 2008). Both oryzanol and ferulic acid possess several physiological proper ties, such a
12、s reduction of serum cholesterol levels (Wilson and others 2007), inhibition of tumor promotion (Yasukawa and others 1998), and protective action against liver injury (Choti-markorn and Ushio 2008). Oxidative stress is regarded as the key factor in the development of diabetes and its associated heal
13、th disorders. The high-fat diet fed C 57BL/6 mouse model has long been used by researchers in investigating the pathophysiology of impaired glucose tolerance and type 2 diabetes and for the development of new treatments (Surwit and others 1988; Surwit and other s 1991; Schreyer and others 1998; Winz
14、ell and Ahren 2004). Since diabetes is a free radical mediated disease, the strong antioxidant activity of oryzanol and ferulic acid may be useful in preventing the development of diabetic hyperglycemia under a high-fat diet. There are limited reports on the physiological functions of these phenolic
15、 compounds in relation to glucose metabolism in animal models. Thus, this study was conducted to investigate the effects of dietary feeding of oryzanol and ferulic acid on the glucose metabolism in high-fat-fed C57BL/6 mice.1. Materials and Methods1.1 Animals and dietsTwenty-four male C57BL/6N mice
16、of 4 wk of age, weighing 12 g, were obtained from Orient Inc. (Seoul, Korea). They were individually housed in stainless steel cages in a room maintained at 25C with 50% relative humidity and 12/12 h light/dark cycle and fed with a pelletized chow diet for 2 wk after arrival. The mice were then rand
17、omly divided into 4 dietary groups (n = 6). The 1st and 2nd groups were fed with a normal and high-fat (17%, w/w) diets, respectively, while the other 2 groups were fed with high-fat diet supplemented with either 0.5% oryzanol or 0.5% ferulic acid (98% pure, Tsuno, Osaka, Japan). The composition of
18、the experimental diet (Table 1) was based on the AIN-76 semisynthetic diet. The mice were fed for 7 wk and allowed free access to food and water during the experimental period. The body weight gain was measured weekly. At the end of the experimental period, the mice were anaesthetized with 60-L Keta
19、mine-HCl following a 12 h fast and sacrificed. Blood samples were collected and centrifuged at 1000 g for 15 min at 4C to obtain the plasma. The livers were removed, rinsed with physiological saline, and stored at 70C until analysis. The current study protocol was approved by the Ethics Committee of
20、 Kyungpook Natl. Univ. for anima studies.1.2 Measurement of blood glucose levelThe blood glucose level in mice was measured using Accu-Chek Active Blood Glucose Test Strips (Roche Diagnostics GmbH, Germany). Blood samples were drawn from the tail vein of the mice before and after 3 and 7 wk of feedi
21、ng the animals with experimental diets. 1.3 Determination of glycogen and insulin levelsThe glycogen concentration in liver was determined using the method described by Seifter and others (1950)。 Fresh liver (100 mg) was mixed with 30% KOH and heated at 100C for 30 min. The mixture was then added wi
22、th 1.5 mL ethanol (95%) and kept over night at 4C. The pellet was mixed with 4 mL distilled water. A 500 L of the mixture was added with 0.2% anthrone (in 95% H2SO4) and the absorbance of the sample solution was measured at 620 nm. The results were calculated on the basis of a standard calibration c
23、urve of glucose. The insulin content was measured using enzyme-linked immunosorbent assay (ELISA) kits (TMB Mouse Insulin ELISA kit, Sibayagi, Japan).1.4 Measurement of hepatic glucose-regulating enzyme activitiesThe hepatic enzyme source was prepared according to the method developed by Hulcher and
24、 Oleson (1973). The glucokinase (GK) activity was determined based from the method of Davidson and Arion (1987) with slight modification. A 0.98 mL of the reaction mixture containing 50 mM Hepes-NaOH(pH 7.4), 100 mM KCl, 7.5 m M MgCl2, 2.5 mM dithioerythritol, 10 mg/mL albumin, 10 mM glucose, 4 unit
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