Phytomedicine 19 (2011) 88–97 Contents lists available at ScienceDirect Phytomedicine jou rn al hom epage: www.elsevier.de/phymed Protective and ameliorative effects of maté (Ilex paraguariensis) on metabolic syndrome in TSOD mice Ghazi M.E. Hussein a,b , Hisashi Matsuda a , Seikou Nakamura a , Toshihito Akiyama b , Kouhei Tamura b , Masayuki Yoshikawa a,∗ a Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan b Tamura Pharmaceutical Co. Ltd., Gose-shi, Nara 639-2295, Japan a r t i c l e i n f o Keywords: Maté Ilex paraguariensis Metabolic syndrome Insulin resistance Adiponectin a b s t r a c t Yerba maté (mate) tea, a herbal tea prepared from the leaves of Ilex paraguariensis, is widely consumed in southern Latin America, and is gaining popularity worldwide. We investigated effects of an aqueous extract of mate on metabolic syndrome features in a metabolic syndrome model Tsumura Suzuki obese diabetic (TSOD) mouse. Oral administration of mate (100 mg/kg) for 7 weeks induced significant decreases in body weight, body mass index, and food intake in TSOD. It significantly decreased the hyperglycemia by reducing fasting blood glucose level, and increasing glucose uptake in glucose tolerance test. It also showed significant improvement in insulin sensitivity by increasing glucose uptake in insulin tolerance test, increasing quantitative insulin sensitivity check index, and decreasing homeostasis model assess- ment of insulin resistance index. The results also showed significant effects of mate on hyperlipidemia by decreasing blood levels of triglycerides, non-esterified fatty acids, and total cholesterol. Moreover, mate significantly improved adiponectin (AD) level, and exhibited significant reduction in white adi- pose tissue weight, and adiposity index in TSOD. It also showed significant ameliorative effects on TSOD histopathology, by reducing adipocytes proliferation, and improving hepatic steatosis. Furthermore, mate administration induced a dose-dependent delay in gastric emptying. The current data suggest that mate ameliorates metabolic syndrome by mechanisms involving increase of peripheral insulin sensitivity and cellular glucose uptake, and by modulating the level of circulating lipid metabolites and AD. These results indicate that mate can induce protective and ameliorative effects on insulin resistance, diabesity, and dyslipidemia in metabolic syndrome. © 2011 Elsevier GmbH. All rights reserved. Introduction Metabolic syndrome, a clustering of multiple metabolic abnormalities and cardiovascular risk factors including obesity, hyperlipidemia, insulin resistance (InsR) and hypertension (Alberti et al. 2005), is worldwide growing epidemic lifestyle disease (Eckel et al. 2005). Its risks are directly influenced by environmental lifestyle (diet and exercise) and genetic factors (Nugent 2004). Recent studies and reviews reported that clinical and research def- initions of metabolic syndrome are focused on obesity and InsR, with some specific ethnic group-related definitions. To date, no drugs are approved specifically for treating metabolic syndrome (Matfin 2008). Current treatment of metabolic syn- drome indications may include one or more pharmacological therapies, mainly statins (3-hydroxy-3-methylglutaryl coenzyme A inhibitors), angiotensin converting enzyme inhibitors, fibrates ∗ Corresponding author. Tel.: +81 75 595 4634; fax: +81 75 595 4768. E-mail address: myoshika@mb.kyoto-phu.ac.jp (M. Yoshikawa). and thiazolidinediones (Scott 2003), in addition to lifestyle changes, diet and physical activities. Recent reports suggest a number of potential drug targets for new therapies for metabolic syndrome (Flordellis et al. 2005; Yamada et al. 2008). A few current reports described some proven complementary and alternative therapies (Hollander and Mechanick 2008), and some natural products and medicines (Ba˜ nos et al. 2008; Minich and Bland 2008) as candidates against metabolic syndrome and InsR. Yerba maté (mate) tea is a herbal tea prepared from the leaves of Ilex paraguariensis St. Hill (Aquifoliaceae). It is widely con- sumed in South America, and is gaining interest and popularity worldwide (Heck and De Mejia 2007). Mate extract is used in complementary and alternative medicine as a mild CNS stimu- lant, diuretic, and in weight reducing preparations (Heck and De Mejia 2007). It contains methyl xanthine alkaloids (majorly caffeine and theobromine), vitamins (vit A, the B complex, C and E), urso- lic acid-derived saponins, and phenolics including caffeoylquinic acid derivatives (majorly chlorogenic acid), flavonoids (e.g. rutin), and tannins (Heck and De Mejia 2007; Bastos et al. 2007). Mate polyphenols level is higher than those of green tea, and parallel to 0944-7113/$ – see front matter © 2011 Elsevier GmbH. All rights reserved. doi:10.1016/j.phymed.2011.06.036