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Potential Role of Cinnamaldehyde and Costunolide to Counteract Metabolic Syndrome Induced by Excessive Fructose Consumption Ayat S

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Potential Role of Cinnamaldehyde and Costunolide to Counteract Metabolic Syndrome Induced by Excessive Fructose Consumption Ayat S Rashwan et al. Beni-Suef University Journal of Basic and Applied Sciences Beni-Suef University Journal of (2019) 8:17 https://doi.org/10.1186/s43088-019-0025-9 Basic and Applied Sciences RESEARCH Open Access Potential role of cinnamaldehyde and costunolide to counteract metabolic syndrome induced by excessive fructose consumption Ayat S. Rashwan* , Marwa A. El-Beltagy, Sherif Y. Saleh and Ibrahim A. Ibrahim* Abstract Background: One of the serious public health problems in the world is metabolic syndrome. It includes visceral obesity, dyslipidemia, insulin resistance, hyperglycemia, and hypertension. As a contributor to almost all the classic signs of metabolic syndrome, fructose was the ideal choice. There are certain shortcomings with existing drugs for insulin-resistant treatment. Plants still represent the main source of most available medicines. Cinnamaldehyde (CNA) is an active principle of Cinnamomum zeylanicum. Costunolide (CE) is natural sesquiterpene lactones, which is the main bioactive constituent of Saussurea lappa. The main aim of the present study is to investigate the effect of the synthetic antidiabetic agent (metformin) in comparison with natural constituents (cinnamaldehyde, costunolide) after developing a reliable model for insulin resistance by using high fructose diet (HFD). Results: It was found that HFD increased plasma glucose, insulin, glycosylated hemoglobin, HbA1c, serum total cholesterol, LDL-cholesterol, triglyceride, ALT, AST, creatinine, and uric acid. Moreover, HFD decreased hepatic reduced glutathione and superoxide dismutase levels. While oral administration of cinnamaldehyde and costunolide significantly decreased plasma glucose, HbA1c, total cholesterol, LDL-cholesterol, triglyceride, and increased level of hepatic reduced glutathione and superoxide dismutase activity. Also, cinnamaldehyde and costunolide restored the altered plasma levels of ALT, AST, creatinine, and uric acid to normal. Conclusions: The results of this experimental study showed that cinnamaldehyde and costunolide could be used as safe drugs for treating different abnormalities of metabolic syndrome. Keywords: Metabolic syndrome, Fructose, Cinnamaldehyde, Costunolide, Insulin resistance 1 Background 28]. It has a unique metabolism that leads to an increase in The incidence of metabolic syndrome has risen world- lipogenesis and oxidative stress [3]. Consumption of wide mostly because of the extreme consumption of fructose for the long term is accompanied by diabetes in energy-dense foods and reduced physical activity. It ele- addition to insulin resistance and metabolic syndrome in vates the risk of developing many serious diseases as human in addition to experimental animals [6]. The rats type 2 diabetes mellitus (T2DM), cardiovascular diseases fed fructose 6 weeks provide an ideal model for insulin (CVD), cancer, nonalcoholic fatty liver disease (NAFLD), resistance study [34]. infertility, dementia, and other diseases [2]. Metformin, one of biguanide glucose–lowering drugs, is Fructose is a simple sugar, a monosaccharide found in considered the first medicine prescribed orally for people abundance in added dietary sugars, fruit, and honey [27, with T2DM [15]. In spite of using metformin for numerous years, it has only recently been valued as an insulin sensitizer [21]. Transcinnamaldehyde, an essential oil in cinnamon * Correspondence: [email protected]; [email protected] Department of Biochemistry, Faculty of Vet. Medicine, Suez Canal University, bark, is the cause of the prominent smell and taste of Ismailia, Egypt © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Rashwan et al. Beni-Suef University Journal of Basic and Applied Sciences (2019) 8:17 Page 2 of 8 cinnamon [10]. Cinnamaldehyde represents 98% of the 2.3 Induction of insulin resistance components of cinnamon oil [62]. Cinnamaldehyde has Insulin resistance was triggered by consumption of 60% several biological activities such as hypoglycemic, antihy- fructose mixed with standard rat chow for 10 weeks. perlipidemic, and anticancer activities [51, 56]. The selected percentage of fructose was based on previ- Costunolide is a well-known sesquiterpene lactone ous study for inducing insulin resistance in rats de- that is considered as important herbal treatment, with scribed by [34]. anti-inflammatory, anti-fungal, anti-viral properties, anti- pyretic, anti-ulcer, and antimycobacterial activities [46]. 2.4 Experimental design and treatment In addition to the powerful ability of costunolide to de- Experimental animals were divided randomly into 5 cline serum total cholesterol (TC), LDL-cholesterol and groups (each group contains 8 rats) as the following. triglyceride (TG), it also elevates plasma insulin, tissue glycogen, serum protein, and HDL-cholesterol [55]. Group I: Normal control rats that received standard rat The objective of the current study was the comparison ration all over the experiment without treatment. of the effect of cinnamaldehyde and costunolide on a Group II: Received HFD all over the experiment weeks model of insulin resistance induced by the consumption as an insulin resistance model. of high fructose diet. Group III: Received HFD for 10 weeks then received cinnamaldehyde at a dose 40 mg/kg described by [57] 2 Methods by oral gavage with HFD for 4 weeks. 2.1 Experimental animals Group IV: Received HFD for 10 weeks then received The current study was carried out on a total number of costunolide at a dose 20 mg/kg described by (James 40 healthy male albino rats; weighing 220–290 g. They [17]) by oral gavage with HFD for 4 weeks. were housed in metal cages in an air-conditioned room Group V: Received HFD for 10 weeks then received maintained at 22 ± 2 °C with a 12-h light/12-h dark cycle metformin at a dose 300 mg/kg described by [39]by and allowed free access to food and water. They were oral gavage with HFD for 4 weeks . maintained on a standard balanced ration for 2 weeks accommodation (Table 1) according to [40]. Treatments were administered once daily for 4 weeks. The positive and negative control groups were given an equivalent volume of DMSO 25%. 2.2 Drugs and chemicals Blood samples were taken at the end of the experi- ment from all groups after overnight fasting from retro- Fructose was purchased as white crystals (Safety orbital venous plexus then serum was obtained directly Misr, Specialized Food Industry Co., Cairo, Egypt). by centrifugation. Cinnamaldehyde was obtained as a light yellow color After collection of blood samples, rats were euthanized liquid from Sigma-Aldrich (St. Louis, Missouri, by inhalant anesthetic overdose using a bell jar followed USA). by cervical dislocation. Costunolide was supplied as a white powder from Cinnamaldehyde and costunolide were prepared with Herbest (Baoji Herbest Bio-Tech Co., Ltd). mixing in 25% of DMSO for oral administration to rats Metformin HCl (Cidophage) was supplied as tablets while metformin tablets were crushed with a pestle and from CID Company, Cairo, Egypt. mortar then dissolved in distilled water for oral adminis- Dimethyl sulfoxide (DMSO) was purchased from s d tration to rats. fine-chem limited (SDFCL), Mumbai-30, India. 2.5 Estimation of fasting blood glucose level Table 1 Composition of standard balanced ration (g / Kg diet) Fasting blood glucose was estimated by glucose oxidase Ingredients Amounts (g) peroxidase method [52]. Poultry meal 300 Yellow corn 480 2.6 Estimation of fasting blood insulin Sucrose 50 Insulin is estimated by using Rat Insulin ELISA Kits, Fine wheat bran 90 Catalog Number:-MBS289124 according to [18]. Linseed oil 40 Premix 37 2.7 Estimation of glycosylated hemoglobin Fully automated auto-analyzer Cobas C311 (Roche Diag- Methionine 2 nostics, Germany) was used in glycosylated hemoglobin Choline 1 (HbA1c) estimation. Rashwan et al. Beni-Suef University Journal of Basic and Applied Sciences (2019) 8:17 Page 3 of 8 2.8 Calculation of HOMA-IR index 3.2 Effect of cinnamaldehyde and costunolide on fasting Homeostasis model assessment of insulin resistance blood glucose, insulin, HbA1c %, and HOMA-IR (HOMA- IR) index was calculated according to the follow- There was a significant increase in fasting blood glucose, in- ing formula: sulin, HbA1c %, and HOMA-IR in HFD treated group (Fasting blood insulin (U/L) × Fasting blood glucose when compared with normal control group. Cinnamalde- (mg/dL)/405) hyde- and costunolide-treated groups showed a significant decrease in fasting blood glucose level when compared with 2.9 Estimation of lipids profile HFD-treated group. On the other hand, cinnamaldehyde- TC, TG, and HDL-cholesterol levels in plasma were esti- treated group showed a significant decrease in fasting blood mated using kits Biomed Diagnostics, Badr City, Egypt. glucose level when compared to costunolide. Also, cinna- Friedewald’s equation is used in LDL-cholesterol level maldehyde treated group showed a significant increase in calculation [19]. blood insulin level when compared with normal control group. Moreover, costunolide- and metformin-treated 2.10 Estimation of antioxidants groups showed no difference in blood insulin level when Determination of reduced glutathione
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