The effects of Momordica charantia on obesity and lipid profiles of mice fed a high-fat diet

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1 Nutrition Reserch nd Prctice 2015;9(5): c2015 The Koren Nutrition Society nd the Koren Society of Community Nutrition The effects of Momordic chrnti on obesity nd lipid profiles of mice fed high-ft diet Jun Wng nd Ho Kyung Ryu Deprtment of Food Science nd Nutrition, Pusn Ntionl University, Busndehk-ro, 63beon-gil, Geumjeong-gu, Busn , Kore BACKGROUND/OBJECTIVES: The present study ws conducted to investigte the effects of dried Momordic chrnti queous extrcts (MCA) nd ethnol extrcts (MCE) on obesity nd lipid profiles in mice fed high-ft diet. MATERIALS/METHODS: Forty two ICR mice were rndomly divided into six groups. The norml group ws fed bsl diet, nd other groups were fed 45% high-ft diet (HFD) for 7 weeks. The norml nd HFD groups were lso orlly dministered distilled wter ech dy for 7 weeks. The remining groups received Momordic chrnti extrct (0.5 or 1.0 g/kg/dy MCA, nd 0.5 or 1.0 g/kg/dy MCE). In order to mesure the nti-obesity nd lipid profile improvement effects, body nd viscerl tissue weight, lipid profiles, plsm insulin levels, heptic mlondildehyde (MDA) levels nd superoxide dismutse (SOD) ctivity were mesured. RESULTS: Both MCA nd MCE significntly decresed body nd viscerl tissue weight reltive to those of the HFD group (P < 0.05). Additionlly high doses of MCE nd MCA significntly reduced the plsmtic insulin levels compred to the HFD groups (P < 0.05) to concentrtions comprle to those found in the norml group. MCA nd MCE supplementtion lso significntly modulted the lipid profiles in plsm, liver, nd feces compred to mice fed the HFD (P < 0.05). Furthermore MCA nd MCE significntly incresed heptic SOD ctivity, nd reduced MDA genertion in the liver of the HFD mice (P <0.05). CONCLUSIONS: Results from the present study suggest tht Momordic chrnti extrcts hve nti-obesity effects nd the ility to modulte lipid prolife of mice fed HFD by suppressing body weight gin, viscerl tissue weight, plsm nd heptic lipid concentrtions, nd lipid peroxidtion long with incresing lipid metolism. Nutrition Reserch nd Prctice 2015;9(5): ; doi: /nrp ; pissn eissn Keywords: Momordic chrnti, ICR mouse, obesity, lipid profiles, weight INTRODUCTION 6) In 1997, obesity ws declred mjor public helth problem nd globl epidemic by the World Helth Orgniztion (WHO). The rte of obesity hs globlly incresed drmticlly during the lst three decdes. Over 200 million men nd nerly 300 million women were obese in 2008 ccording to the estimtes mde by the WHO [1]. The proportions of obese people hve incresed in Asi [2]. In South Kore, mrked environmentl nd lifestyle chnges hve occurred during the recent decdes. Due to incresed lcohol intke nd decresed physicl ctivity, the number of obese ptients hs significntly risen in South Kore. Additionlly the prevlence of obesity-relted diseses hs lso incresed remrkly [3]. In Chin, lifestyle hs lso chnged lot since reforms hve been mde nd the country opened up. An incresingly common high-ft, low-crbohydrte diet nd generl decline in physicl ctivity intensity hs led to the rpid growth of obesity rtes mong Chinese people. The prevlence of overweight nd obese Chinese ws 23.2%, close to qurter of the totl popultion. In Chin, obesity hs become n importnt epidemic disese. To keep mintin helth nd increse the qulity of life, mny people re looking for the wys to tret obesity nd promote weight loss [4]. Obesity is n underlying risk fctor for crdiovsculr disese [5]. Ptients suffering from crdiovsculr disese usully hve incresed blood cholesterol nd low density lipoprotein cholesterol levels, s well s elevted lipid peroxidtion ctivity [6]. Furthermore obesity is mjor risk fctor for dyslipidemi [7]. Thus, obesity is closely ssocited with lipid profiles. Hyperlipidemi is considered to be mjor risk fctors for therosclerosis, myocrdil infrction, hert ttcks, stoke, nd cerebrovsculr diseses [6]. Lipid peroxidtion cn dmge to cell membrnes, lipoproteins nd other lipid-contining structures. This process cn further influence the norml function of cells. Mny humn diseses, such s cncer, vsculr sclerosis, nd ging re ssocited with lipid peroxidtion [8]. Momordic chrnti is climber belonging to the fmily Cucurbitcee nd hs not been widely used in South Kore. However this plnt hs long been consumed s food nd medicine in mny countries, including Chin, Indi, Mly, Thilnd [9]. In Chinese nd Ayurvedic trditionl medicine, Momordic chrnti hs been typiclly used to tret hypogly- Corresponding Author: Ho Kyung Ryu, Tel , Fx , Emil. Received: June 9, 2014, Revised: Jnury 19, 2015, Accepted: Mrch 18, 2015 This is n Open Access rticle distributed under the terms of the Cretive Commons Attribution Non-Commercil License ( which permits unrestricted non-commercil use, distribution, nd reproduction in ny medium, provided the originl work is properly cited.

2 490 Momordic chrnti on obesity nd lipid profiles cemic nd dietes [10]. In previous studies, this plnt ws reported to hve effect on dietic complictions s well s ntibcteril, ntivirl (including nti-hiv), ortifcient, ntifertility, nti-ulcer, nd ntimlril ctivities long with immunomodultory ctivity nd miscellneous effects [11]. In mice fed high-ft diet (HFD), freeze-dried Momordic chrnti juice ws found to possess potentil for reducing diposity nd extrcts from this plnt my reduce viscerl obesity [12,13]. However, no study out the nti-obesity nd lipid improvement effects of Momordic chrnti extrcts in mice fed HFD hs been conducted. In freeze-dried Momordic chrnti juice, portion of the dietry fiber could remin. Therefore, the diposity reduction effect of Momordic chrnti juice might be prtly due to the presence of dietry fiber. For prcticl pplictions, fresh Momordic chrnti is difficult to preserve for long time nd hs bitter tste. In Chin, dried Momordic chrnti hs been widely used to mke te. Therefore, the queous extrct nd ethnol extrct of dried Momordic chrnti ws evluted in the present study. The im of this investigtion ws to determine the effects of Momordic chrnti extrcts on obesity nd lipid profiles of mice fed HFD. MATERIALS AND METHODS Extrcts preprtion Dried Momordic chrnti ws purchsed from Yngwon Food (Chungcheongnmdo, Kore). The plnt were deseeded nd ground to powder. The queous extrct (MCA) ws recovered by boiling 300g of Momordic chrnti powder in 3L of wter for 1 hour three times. The mixtures were filtered with filter pper (Whtmn No.20). The filtrtes were concentrted, lyophilized nd freeze-dried. The ethnol extrct (MCE) ws prepred by mixing 300g of Momordic chrnti powder with 3L of 70% ethnol for 3 dys. The extrct ws filtered nd the residue underwent re-extrction under sme conditions. The filtrtes were combined, concentrted, lyophilized nd freeze-dried. The verge yield obtined for the MCA nd MCE ws out 30% nd 23%, respectively. Chemicls Phosphte buffered sline (PBS), HEPES buffer were purchsed from Biosesng Inc. (Gyonggi-do, Kore). Chloroform ws obtined from Junsei Chemicl Co. (Tokyo, Jpn). Methyl lcohol ws purchsed from Hymn Limited (Essex, Englnd). All chemicls were of nlyticl grde. Animls Five-week-old mle ICR mice were purchsed from Centrl L Animl, Inc. (Seoul, Kore) nd mintined t 23 ± 1 C with 12-h light-drk cycle during the entire experimentl procedure. The ICR mouse is generl-purpose model used for studies in wide rnge of fields including toxicity, phrmcology, drug efficcy, immunology, ging, nd nutritionl biochemicl reserch [13]. After 1 week of cclimtion, the nimls were rndomly divided into six groups of, seven mice ech. The mice were housed in stinless steel cges, nd ll hd free ccess to wter nd food. Animls in the norml group were fed bsl diet (Diet 12450B, Reserch Diets. Inc) with 10% ft nd mice in the other groups were fed HFD with 45% ft (Diet 12451, Reserch Diets. Inc) for 7 weeks. Compositions of diets re shown in Tle 1. The norml nd HFD control groups were orlly dministered distilled wter ech dy for 7weeks. The other four groups received 0.5 g/kg/dy MCA, 1.0 g/kg/dy MCA, 0.5 g/kg/dy MCE, or 1.0 g/kg/dy MCE. LD50 for the MCE is mg/100 g body weight. The dosges of Momordic chrnti extrcts used in the current study were fr less thn the LD50. Body weight nd food intke were mesured once week. All niml experiment procedures were pproved by Pusn Ntionl University-Institutionl Animl Cre nd Use Committee (PNU-IACUC; pprovl number PNU ). Smple collection At the end of the feeding period, the mice were scrificed using ethyl ether fter 12 hours of fsting. Blood smples were collected from the inferior ven cv in tubes contining sodium citrte s n nticogulnt. Plsm ws recovered by centrifugtion t 3,000 rpm for 20 minutes t 4 C. The plsm ws frozen t -80 C until further nlysis. The liver, kidney, spleen, testis, nd testis ft were removed nd weighed. The liver ws divided into five prts nd stored t -80 C for nlysis. Slices of liver were preserved in formlin for histologicl nlysis. Plsm sprtte minotrnsferse (AST), Alnine minotrnsferse (ALT), nd insulin levels AST nd ALT levels in plsm were mesured by using commercilly ville kit (AM101-K; Asn Phrm., Kore). The plsm insulin levels were determined using n insulin mouse ELISA kit (KMC2281; Novex, USA). Plsm lipid profiles The plsm triglyceride (TG), plsm totl cholesterol (TC) nd high-density lipoprotein cholesterol (HDL-C) levels were mesured using commercilly ville kits (AM157S-K, AM 202-K, nd AM 203-K; Asn Phrm.). The low-density lipoprotein cholesterol (LDL-C) levels were clculted s follows: LDL-C = TC - HDL-C Heptic lipid profiles To determine the heptic TG nd TC concentrtions, frozen liver tissues were mixed with volume of PBS buffer 10 times the weight of the tissue nd homogenized. The liver homogente ws centrifuged t 1600 x g for 10 minutes t 4 C nd the superntnt ws stored on ice for nlysis. The concentrtions of TG nd TC in liver were mesured using the sme kits (AM157S-K nd AM 202-K; Asn Phrm.) nd identicl methods s those performed for the plsm. Lipid peroxide nd ntioxidnt enzyme ctivity in liver In order to determine heptic mlondildehyde (MDA) concentrtions, the liver homogente ws nlyzed with commercilly ville kit (TBARS ssy kit; Cymn Chemicl Compny, USA). For the superoxide dismutse (SOD) ssy, frozen liver tissue ws mixed with volume of HEPES buffer 10 times tht of the tissue weight nd homogenized. SOD ctivity in the superntnt ws mesured with corresponding commercil

3 Jun Wng nd Ho Kyung Ryu 491 kit (SOD ssy kit; Cymn Chemicl Compny). Fecl lipids profiles To ssess fecl TG nd TC concentrtions, fecl mteril ws freeze-dried nd mixed with volume of CHCl 3 nd MeOH solution (2:1, v:v) 10 times tht of the fecl mteril weight. After 4 hours of extrction, the mixture ws centrifuged t 800 x g for 20 minutes t 4 C nd the superntnt ws recovered. The fecl level of TG nd TC were mesured using the sme kits (AM157S-K nd AM 202-K, Asn Phrm.) nd identicl methods s those used for plsm nd liver nlyses. Histologicl nlysis The liver smples preserved in formlin were embedded in prffin wx nd cut into section 4-μm thick. Next, the liver section ws stined with hemtoxylin nd eosin (H&E; Sigm- Aldrich, St. Louis, MO, USA). Morphologicl fetures of the heptocytes were observed using light microscopy t 400 mgnifiction [14]. Sttisticl nlysis All dt re expressed s the men ± stndrd error of the men. A one wy nlysis of vrince (ANOVA) followed by Duncn s multiple rnge test were performed to identify significnce differences mong the groups. P-vlues < 0.05 were considered significnt. All sttisticl nlyses were performed with the SPSS progrm (ver.21). RESULTS Body weight, food intke, nd viscerl tissue weight As shown in Tle 2, the initil body weights of the mice in the six groups were sttisticlly identicl. After 7 weeks of orl dministrtion, the finl body weight of mice in the HFD group (44.47 ± 2.36 g) ws 20.74% higher compred to nimls in the norml group (36.83 ± 2.84 g, P < 0.05). Finl body weights of the Momordic chrnti-treted groups (MCA0.5, ± 2.07 g; MCA1, ± 3.82 g; MCE0.5, ± 2.25 g; nd MCE1, ± 2.52 g) were significntly lower (P < 0.05) thn tht of the HFD group. There ws no difference in food intke between the HFD nd Momordic chrnti- treted mice. However, food intke of the norml group ws significntly higher thn of the other groups (P <0.05). Tle 1. Ingredient composition of diets Ingredient Bsl diet (%) HF diet (%) Csein, 80 Mesh L-Csein Corn Strch Mltodextrin Sucrose Cellulose, BW Soyben Oil Lrd DiClcium Phosphte 0 0 Clcium Crbonte 0 0 PotssiumCitrte H2O 0 0 Vitmin Mix V Choline Bitrtrte HF: high-ft The reltive kidney weight nd reltive testicle weight did not differ significntly mong the six groups. In contrst, mice in the HFD group hd higher reltive liver weight, nd reltive spleen weight, reltive testicle ft weight compred to the norml group (P < 0.05). The reltive liver weights of the Momordic chrnti-treted groups (MCA0.5, 3.37 ± g/g; MCA1, 3.35 ± g/g; MCE0.5, 3.28 ± g/g; nd MCE1, 3.25 ± g/g) were significntly lower (P < 0.05) thn tht of the HFD groups (3.83 ± g/g). Reltive spleen weights of the MCE-treted mice (MCE0.5, 0.24 ± g/g nd MCE1, 0.22 ± g/g) were lower (P <0.05) thn tht of the HFD group (0.33 ± g/g). Additionlly, mice in the MCE1 group hd lower reltive testicle ft weight (1.81 ± g/g) compred to tht of the HFD group (4.10 ± g/g; P < 0.05). Plsm AST nd ALT levels Both AST nd ALT levels re commonly used to identify the liver dmge [15]. Plsm AST nd ALT levels mesured in the current study re shown in Tle 3. Plsm AST nd ALT levels of mice only fed the HFD were found to be significntly higher thn tht of mice in ll norml groups. Plsm AST levels of the Momordic chrnti-treted groups (MCA0.5, ± 2.93 Krmen units/ml; MCA1, ± 1.89; MCE0.5, ± 0.72 Krmen units/ml; nd MCE1, ± 4.24 Krmen units/ml) were Tle 2. Effect of Momordic chrnti extrcts on body weight, food intke, nd tissue weight HFD + momordic chrnti extrcts Group Norml HFD MCA0.5 MCA1 MCE0.5 MCE1 Initil body weight (g) ± ± ± ± ± ± 0.32 Finl body weight (g) ± ± 2.36 c ± 2.07 b ± ± ± 2.52 Food intke (g) 3.83 ± 0.38 b 3.31 ± ± ± ± ± 0.15 Liver weight (g/g B.W.) 3.30 ± ± 0.42 b 3.37 ± ± ± ± 0.36 Kidney weight (g/g B.W.) 1.35 ± ± ± ± ± ± 0.31 Spleen weight (g/g B.W.) 0.25 ± ± 0.11 c 0.29 ± 0.11 bc 0.27 ± 0.06 bc 0.24 ± ± 0.04 Testicle weight (g/g B.W.) 0.53 ± ± ± ± ± ± 0.07 Testicle ft weight (g/g B.W.) 2.07 ± ± 0.99 c 4.00 ± 1.13 c 3.35 ± 1.04 bc 2.90 ± 1.22 c 1.81 ± 1.34 Vlues re presented s men±sd (n=6). The different letters in sme line indicte sttisticlly significnt difference (P < 0.05) ccording to Duncn's multiple rnge test. Tissue weight ws expressed s tissue weight (g) 100/finl body weight. HFD: high-ft diet; MCA0.5: Momordic chrnti queous extrcts 0.5 g/kg/dy; MCA1: Momordic chrnti queous extrcts 1 g/kg/dy; MCE0.5: Momordic chrnti ethnol extrcts 0.5 g/kg/dy; MCE1: Momordic chrnti ethnol extrcts 1 g/kg/dy

4 492 Momordic chrnti on obesity nd lipid profiles Tle 3. Effect of Momordic chrnti extrcts on liver function HFD + Momordic chrnti extrcts Group Norml HFD MCA0.5 MCA1 MCE0.5 MCE1 AST (Krmen unit/ml) ± ± 3.85 d ± 2.93 c ± 1.89 b ± 0.72 c ± 4.24 b ALT (Krmen unit/ml) ± ± 2.04 b ± 1.28 b ± ± 4.94 b ± 3.67 Vlues re presented s men±sd (n=6). The different letters in sme line indicte sttisticlly significnt difference (P < 0.05) ccording to Duncn's multiple rnge test. HFD: high-ft diet; MCA0.5: Momordic chrnti queous extrcts 0.5 g/kg/dy; MCA1: Momordic chrnti queous extrcts 1 g/kg/dy; MCE0.5: Momordic chrnti ethnol extrcts 0.5 g/kg/dy; MCE1: Momordic chrnti ethnol extrcts 1 g/kg/dy; AST: sprtte minotrnsferse; ALT: Alnine minotrnsferse Tle 4. Effect of momordic chrnti extrcts on plsm, heptic nd fecl lipid levels HFD + momordic chrnti extrcts Group Norml HFD MCA0.5 MCA1 MCE0.5 MCE1 In plsm TG (mg/dl) ± ± c ± b ± b ± ± TC (mg/dl) ± ± c ± c ± b ± bc ± HDL-C (mg/dl) ± bc ± ± ± ± c ± c LDL-C (mg/dl) ± 4.18 b ± d ± c ± c ± c ± 2.69 In liver TG (mg/g liver) 9.41 ± ± 1.61 d ± 0.28 c 8.69 ± ± 0.41 b 9.16 ± 0.53 TC (mg/g liver) 6.45 ± ± 1.90 b 6.72 ± ± ± 2.16 b 6.85 ± 1.36 In feces TG (mg/g feces) 9.27 ± ± ± ± ± ± 2.77 b TC (mg/g feces) 7.87 ± ± ± ± ± ± 0.07 Vlues re presented s men±sd (n=6). The different letters in sme line indicte sttisticlly significnt difference (P < 0.05) ccording to Duncn's multiple rnge test. HFD: high-ft diet; MCA0.5: momordic chrnti queous extrcts 0.5 g/kg/dy; MCA1: momordic chrnti queous extrcts 1 g/kg/dy; MCE0.5: momordic chrnti ethnol extrcts 0.5 g/kg/dy; MCE1: momordic chrnti ethnol extrcts 1 g/kg/dy; TG: totl triglyceride; TC: totl cholesterol; HDL-C: high density lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol significntly lower (P < 0.05) compred to tht of the HFD group (36.17 ± 3.85 Krmen units/ml; P < 0.05). Additionlly ALT ctivity in mice fed high dose of MCA (16.60 ± 2.00 Krmen units/ml) or MCE (16.75 ± 3.67 Krmen units/ml) ws lso significntly lower (P < 0.05) thn tht of the HFD group (23.61 ± 2.04 Krmen units/ml). Plsm insulin levels Obesity is ssocited with n increse risk of developing insulin resistnce. To compenste for this resistnce, more insulin is produced. Therefore, insulin levels were mesured. The level of plsm insulin for mice in the HFD group ws significntly higher compred to the norml group (P < 0.05). The insulin levels of mice fed high dose MCE or MCA were lower thn tht of the HFD group (P < 0.05) nd comprle to the level found in the norml group (Fig. 1). Plsm, heptic, nd fecl lipid levels In order to study the effects of Momordic chrnti extrcts on lipid profiles, plsm, heptic, nd fecl lipid levels were mesured. The levels of plsm TC, TG, nd LDL-C in the HFD group were significntly higher thn those in the norml group. Plsm TG levels were significntly higher in the HFD group ( ± mg/dl) thn tht of the norml control group ( ± mg/dl; P < 0.05). Furthermore, plsm TG levels of the Momordic chrnti-treted groups (MCA0.5, ± mg/dl; MCA1, ± mg/dl; MCE0.5, ± mg/dl; nd MCE1, ± mg/dl) were significntly lower compred to the HFD group ( ± mg/dl; P < 0.05). Mice fed high dose of MCA ( ± mg/dl) or MCE ( ± mg/dl) hd lower plsm TC level compred to the HFD group ( ± mg/dl; P < 0.05). Tretment with high dose of MCE (33.76 ± 2.69 mg/dl) significntly lowered plsm TG concentrtions by 185.2% compred to the HFD group (96.31 ± mg/dl). The HDL-C levels of mice in the HFD group (95.32 ± 7.96 mg/dl) were significntly lower thn those of the norml group ( ± mg/dl, P < 0.05). In ddition, MCE-treted mice hd higher HDL-C level (MCE0.5, ± mg/dl nd MCE1, ± mg/dl) compred to the HFD group (P < 0.05). The levels of heptic TC nd TG for the HFD group were significntly higher thn those for the norml group. All of the Momordic chrnti-treted nimls hd lower TG levels (MCA0.5, ± 0.28 mg/dl; MCA1, 8.69 ± 0.44 mg/dl; MCE0.5, 9.50 ± 0.41 mg/dl nd MCE1, 9.16 ± 0.53 mg/dl) thn tht of the HFD group (13.27 ± 1.61 mg/dl; P < 0.05). The heptic TC levels of the MCA- nd high dose MCE-treted group (MCA0.5, 6.72 ± 1.94 mg/dl; MCA1, 6.12 ± 1.24 mg/dl; nd MCE1, 6.85 ± 1.36 mg/dl) were significntly lower reltive to the HFD group (13.27 ± 1.61 mg/dl; P < 0.05). There were no significnt differences in fecl TG levels between the norml nd HFD groups. However, the fecl TG levels of the in MCE1 group were significntly lower thn those of the other groups (P < 0.05). No significnt differences in fecl TC levels were observed mong the groups (Tle 4). Lipid peroxide nd ntioxidnt enzyme ctivity in the liver Lipid peroxidtion is well-estlished mechnism of cellulr injury in both plnts nd nimls nd is used s n indictor of oxidtive stress in cells nd tissues [16]. MDA is nturlly

5 Jun Wng nd Ho Kyung Ryu b Plsm insulin (ng/ml) norml HFD MCA0.5 MCA1 MCE0.5 MCE1 Fig. 1. Effect of momordic chrnti extrcts on plsm insulin. Vlues re presented s men ± SD (n = 6). -b Different letters over the brs indicte tht the men vlues re significntly different (P < 0.05) ccording to Duncn's multiple rnge test. HFD: high-ft diet; MCA0.5: high-ft diet + momordic chrnti queous extrcts 0.5 g/kg/dy; MCA1: high-ft diet + momordic chrnti queous extrcts 1 g/kg/dy; MCE0.5: high-ft diet + momordic chrnti ethnol extrcts 0.5 g/kg/dy; MCE1: momordic chrnti ethnol extrcts 1 g/kg/dy; MDA content(μm) b Norml HFD MCA0.5 MCA1 MCE0.5 MCE1 Fig. 2. Effect of momordic chrnti extrcts on MDA content. Ech vlue is expressed s men ± SD (n = 6). -b Different letters over the brs indicte tht the men vlues re significntly different (P < 0.05) ccording to Duncn's multiple rnge test. HFD: high-ft diet; MCA0.5: high-ft diet + momordic chrnti queous extrcts 0.5 g/kg/dy; MCA1: high-ft diet + momordic chrnti queous extrcts 1 g/kg/dy; MCE0.5: high-ft diet + momordic chrnti ethnol extrcts 0.5 g/kg/dy; MCE1: high-ft diet+ momordic chrnti ethnol extrcts 1 g/kg/dy; MDA: Mlondildehyde SOD ctivity (U/ml) Norml HFD MCA0.5 MCA1 MCE0.5 MCE1 Fig. 3. Effect of momordic chrnti extrcts on SOD ctivity. Ech vlue is expressed s men ± SD (n = 6). -b Different letters over the brs indicte tht the men vlues re significntly different (P < 0.05) ccording to Duncn's multiple rnge test. HFD: high-ft diet; MCA0.5: high-ft diet + momordic chrnti queous extrcts 0.5 g/kg/dy; MCA1: high-ft diet + momordic chrnti queous extrcts 1 g/kg/dy; MCE0.5: high-ft diet + momordic chrnti ethnol extrcts 0.5 g/kg/dy; MCE1: high-ft diet+ momordic chrnti ethnol extrcts 1 g/kg/dy; SOD: superoxide dismutse b Fig. 4. Effects of momordic chrnti extrcts on histopthologic chnges in mice fed high-ft diet. Representtive H&E stined mouse liver smples from (A): Norml group (B): HFD group (C): MCA0.5 group (D): MCA1 group (E): MCE0.5 group (F): MCE1 group. H&E: hemtoxylin nd eosin; HFD: high-ft diet; MCA0.5: high-ft diet + momordic chrnti queous extrcts 0.5 g/kg/dy; MCA1: high-ft diet + momordic chrnti queous extrcts 1 g/kg/dy; MCE0.5: high-ft diet+momordic chrnti ethnol extrcts 0.5 g/kg/dy; MCE1: high-ft diet + momordic chrnti ethnol extrcts 1 g/kg/dy; mgnifiction: 400 occurring product of lipid peroxidtion [17]. SOD is n enzyme tht ctlyzes the dismuttion of the superoxide nion into moleculr oxygen nd hydrogen peroxide. SOD is crucil for the prevention of diseses linked to oxidtive stress [18]. In order to determine the effects of Momordic chrnti on liver lipid peroxidtion in mice, heptic MDA nd SOD levels were exmined. MDA levels in the liver re shown in Fig. 2. MDA concentrtion in the HFD group (36.30 ± 2.11 μm) ws significntly higher thn tht in the norml group (24.10 ± 4.44 μm, P < 0.05). The MDA level in mice treted with high dose of MCE ws significntly lowered by 41.9% compred to the HFD group (P < 0.05). As shown in Fig. 3, there ws no significnt difference in SOD levels when compring the norml nd HFD groups. However mice given high dose of MCE hd higher level of SOD ctivity compred to the other groups (P < 0.05). Histopthologicl nlysis of the heptocytes H&E-stined heptic sections re shown in Fig. 4. Mice in the norml group hd norml histology. No excess lipid ws observed in these nimls. Mice in the HFD group hd severe mcrovesiculr stetosis nd undnt lipid droplets ccumultion inside the prenchym cells. But only slight chnges in dosge groups. Lipid deposition ws reduced remrkly in heptocytes of mice treted with Momordic chrnti extrcts compred to the HFD group. Liver histology of the extrcttreted groups ws similr to tht of the norml group. Overll, histologicl nlysis reveled tht HFD consumption induced lipid ccumultion in the heptocytes tht could be effectively prevented by tretment with Momordic chrnti extrcts. DISCUSSION Momordic chrnti contins bioctive compounds tht include glycosides, sponins, lkloids, fixed oils, triterpenes, proteins nd steroids. Severl phytochemicls such s momorchrins, momordenol, momordolol, chrntin, chrine, cryptoxnthin, cucurbitcins, cyclortenols, diosgenin, eleosteric cids, erythrodiol, glcturonic cids, gentisic cid, goyglycosides,, multiflorenol, hve been isolted [11]. The im of the current study ws to determine the effects

6 494 Momordic chrnti on obesity nd lipid profiles of dried Momordic chrnti extrcts on obesity nd lipid profiles of mice fed HFD. We found tht the extrcts effectively suppressed body weight gin of mice tht consumed HFD. Chen et l. previously demonstrted tht Momordic chrnti juice reduced weight gin without ffecting energy intke or pprent ft sorption [12]. In the present investigtion, Momordic chrnti-s-extrcts treted mice lso hd lower reltive liver weight, spleen weight, nd testicle ft weight thn those of the HFD group. Furthermore, Momordic chrnti ws lso found to suppress the HFD-induced increse in liver weight in study by Shih et l. [19]. Momordic chrnti tretment of 3T3-L1 predipocytes cells resulted in decresed lipid ccumultion. And peroxisome prolifertor-ctivted receptor-γ (PPARγ) expression ws significntly down-regulted with the tretment [18]. So Momordic chrnti extrcts reduced the body weight gin possibly by reducing the expression of PPARγ nd reduce the lipid ccumultion [20]. We lso found tht insulin levels of mice treted with high doses of MCE or MCA were lower thn those of the HFD group nd comprle to the levels of the norml group. The hypoglycemic potentil of Momordic chrnti in norml nd dietic rts or humns with type 2 dietes hs been previously reported [21-23]. This plnt my lso increse insulin-positive cell numbers in the pncres [24] nd improve insulin resistnce [23,25]. In our study, supplementtion with Momordic chrnti extrcts significntly lowered the plsm TG, TC, nd LDL-C levels long with heptic TG nd TC concentrtions in mice fed HFD. Tretment with the extrcts lso elevted plsm HDL-C levels nd fecl TG concentrtion in nimls given the HFD. These findings indicte tht Momordic chrnti extrcts could improve lipid profiles nd lipid metolism. Similr results hve been found in previous studies, Momordic chrnti extrcts were lso discovered to reduce serum cholesterol long with heptic TC nd TG in norml rts [26] while incresing HDL-C in streptozotocin-treted dietic rts [10]. In the present investigtion, mice treted with the Momordic chrnti extrcts hd lower MDA contents nd higher SOD ctivity thn those in the HFD group, indicting tht the extrcts cn significntly suppress lipid peroxidtion. Momordic chrnti extrcts possess potent ntioxidnt nd free rdicl scvenging ctivities. These ntioxidnt ctivities could hve contributed, t lest prtly, to the effect of Momordic chrnti extrcts on suppressing lipid peroxidtion [27]. There ws no significnt difference between MCA or MCE treted groups in generl. But the plsm TG level in MCE treted groups ws significntly lower compred to MCA treted groups. And the plsm TC nd LDL-C level in MCE1 group ws lower thn tht in the MCA treted groups. The plsm MCA treted mice lso hd significntly higher HDL-C level compred to MCE treted groups. So the MCE treted groups perhps hd better effect on the plsm lipid profiles of mice fed high-ft diet. In conclusion, we demonstrted tht Momordic chrnti extrcts hve potent in vitro ntioxidnt ctivity. Furthermore, the extrcts hve nti-obesity effects nd cn improve profiles of lipid improvement effect in mice fed HFD by suppressing body weight, reducing plsm nd heptic lipid concentrtions, nd inhibiting lipid peroxidtion while incresing lipid metolism. REFERENCES 1. Hththotuw RN, Wijeyrtne CN, Senrth U. Worldwide epidemic of obesity. In: Mhmood T, Arulkumrn S, editors. Obesity: A Ticking Time Bomb for Reproductive Helth. London: Elsevier; p Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, Zimmet P, Son HY. Epidemic obesity nd type 2 dietes in Asi. Lncet 2006;368: Oh SW. Obesity nd metolic syndrome in Kore. Dietes Met J 2011;35: Wu YF, M GS, Hu YH, Li YP, Li X, Cui ZH, Chen CM, Kong LZ. 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