The protective role of amla (Emblica officinalis Gaertn.) against fructose-induced metabolic syndrome in a rat model Hyun Young Kim 1,2 , Tsutomu Okubo 3 , Lekh Raj Juneja 3 and Takako Yokozawa 2 * 1 Department of Food Science, Jinju National University, 150 Chilamdong, Jinju 660-758, Korea 2 Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan 3 Bio-nutrition Division, Taiyo Kagaku Co. Ltd, 1 – 3 Takaramachi, Yokkaichi 510-0844, Japan (Received 17 April 2009 – Revised 10 August 2009 – Accepted 11 August 2009 – First published online 2 November 2009) We investigated the effects of amla (Emblica officinalis Gaertn.) on fructose-induced metabolic syndrome using a rat model. Male Wistar rats were fed a high-fructose (65 %) diet or standard chow for 1 week, and treated with an ethyl acetate (EtOAc) extract of amla, a polyphenol-rich fraction, at 10 or 20 mg/kg body weight per d, or vehicle, for 2 weeks. Serum glucose, TAG, total cholesterol and blood pressure levels of the high-fructose diet-fed rats were increased compared with those of the normal rats (P,0·001). However, the EtOAc extract of amla ameliorated the high fructose- induced metabolic syndrome, including hypertriacylglycerolaemia and hypercholesterolaemia. Also, the elevated levels of hepatic TAG and total cholesterol in rats given the high-fructose diet were significantly reduced by 33·8 and 24·6 %, respectively (P, 0·001), on the administration of the EtOAc extract of amla at the dose of 20 mg/kg with the regulation of sterol regulatory element-binding protein (SREBP)-1 expression. The protein levels of PPARa and SREBP-2 were not affected by the feeding of the high-fructose diet or EtOAc extract of amla. In addition, oral administration of the amla extract at the dose of 20 mg/kg significantly inhibited the increased serum and hepatic mitochondrial thiobarbituric acid-reactive substance levels (21·1 and 43·1 %, respectively; P,0·001). Furthermore, the amla extract inhibited the increase of cyclo-oxygenase-2 with the regulation of NF-kB and bcl-2 proteins in the liver, while the elevated expression level of bax was significantly decreased by 8·5 and 10·2 % at the doses of 10 and 20 mg/kg body weight per d, respectively. These findings suggest that fructose-induced metabolic syndrome is attenuated by the polyphenol-rich fraction of amla. Amla: High-fructose diet: Metabolic syndrome: Sterol regulatory element-binding protein-1: NF-kB The incidence of the metabolic syndrome characterised by insu- lin resistance, dyslipidaemia and hypertension is increasing worldwide. This is also associated with increased morbidity and mortality from several prevalent diseases, such as diabetes, cancer, myocardial infarction and stroke. Recent findings have shown that dietary fructose facilitates metabolic derangement and induces oxidative damage (1 – 5) . Also, numerous studies suggest that increased fructose consumption may be an import- ant contributor to the metabolic syndrome (6 – 12) . In addition, a high-fructose diet leads to a well-characterised metabolic syn- drome, typically resulting in hyperinsulinaemia, insulin resist- ance, hypertension, hypertriacylglycerolaemia, dyslipidaemia and a decline in the level of HDL-cholesterol (13,14) . Also, high-fructose diet-fed animals have been shown to exhibit altered lipid metabolism due to hepatic stress as a result of the burden of fructose metabolism (3) . Recently, functional foods which possess antioxidant activity have attracted attention as agents possibly reducing the risk of the metabolic syndrome induced by a high-fructose diet (15 – 21) . Emblica officinalis Gaertn., commonly known as amla, is a member of the small genus of Emblica (Euphorbiaceae). It grows in tropical and subtropical parts of China, India, Indo- nesia and the Malay Peninsula. It is an important dietary source of vitamin C, minerals and amino acids, and also con- tains phenolic compounds, tannins, phyllembelic acid, phyl- lemblin, rutin, curcuminoides and emblicol. All parts of the plant are used for medicinal purposes. Especially, the fruit has been used in Ayurveda as a potent rasayana (22) and tra- ditional medicine for the treatment of diarrhoea, jaundice and inflammation (23) . In addition, the pulp of the fruit is smeared on the head to alleviate headaches and dizziness (24) . Recently, amla extract has been tested for various pharmaco- logical activities. The fruit extract was reported to exhibit hypolipidaemic (25) , antidiabetic (26) and anti-inflammatory activities (27) and inhibit retroviruses such as HIV-1 (28) , tumour development (29) and gastric ulcer (30) . Moreover, amla extract has been shown to exhibit antioxidant properties (31,32) , and it has been reported that the aqueous extract of amla is a potent inhibitor of lipid peroxide formation and a scavenger of hydroxyl and superoxide radicals in vitro (33) . In a previous study, we demonstrated the antioxidative property of amla using Cu 2þ -induced oxidised human LDL (34) . Also, we * Corresponding author: Dr Takako Yokozawa, fax þ81 76 434 5068, email yokozawa@inm.u-toyama.ac.jp Abbreviations: BW, body weight; COX-2, cyclo-oxygenase-2; EtOAc, ethyl acetate; IDL, intermediate-density lipoprotein; I-kBa, inhibitor binding protein kB-a; iNOS, inducible NO synthase; SREBP, sterol regulatory element-binding protein; TBA, thiobarbituric acid; Tris, 2-amino-2-hydroxymethyl-1,3-propanediol. British Journal of Nutrition (2010), 103, 502–512 doi:10.1017/S0007114509991978 q The Authors 2009 British Journal of Nutrition http://dx.doi.org/10.1017/S0007114509991978 Downloaded from http:/www.cambridge.org/core. IP address: 54.162.207.63, on 23 Oct 2016 at 22:01:16, subject to the Cambridge Core terms of use, available at http:/www.cambridge.org/core/terms.