35 GREEN TEA EXTRACT EFFECT ON BLOOD GLUCOSE LEVEL AND LIVER HISTOPATHOLOGY IN DIABETIC MICE Diana Holidah 1 , Fransiska Maria Christianty 1 , Wilda Zidni Ilma 1 Faculty of Pharmacy, University of Jember, Indonesia E-mail: dien_holy@yahoo.com INTRODUCTION Diabetes mellitus is a disorder of hyperglycemia and glucose intolerance due to insulin deficiency, impaired of insulin receptor or both (Unwin et al., 2009). There are generally two types of diabetes are type 1 diabetes (pancreatic beta cell damage caused absolute insulin deficiency) and type 2 (a combination of a lack of insulin production and secretion and sensitivity to insulin receptor) (Dipiro et al, 2008). Diabetes mellitus disease is increasing rapidly in worlwide. The incidences in 2010 were about 285 million people and It has been estimated that by the year 2025, the global incidence of diabetes would increase to 350 million (International diabetes federation, 2006). In diabetes, activation of hepatic gluconeogenesis enzymes can increase glucose production and thus contribute to increase blood glucose which could deteriorate diabetes (Sundaram et al., 2013). The state of diabetes characterized by decreased insulin sensitivity is the major cause of NAFLD (Non - Alcoholic Fatty Liver Disease), because in diabetes state occurs disorders of glucose metabolism and fat so that could result in fibrosis, infiltration, necroinflamation, to acute liver disease (Marchesini et al., 2001). Treatment of diabetes mellitus is chronic and long life, causing undesirable side effects (Unwin et al., 2009). Metformin is an oral hypoglycemic agent, which belongs to the class known as the biguanides. Metformin is now widely used as one of the mainstays in the management of type 2 diabetes. Metformin reduces fasting plasma glucose concentration by reducing rate of hepatic glucose production via gluconeogenesis and glycogenolysis. Metformin improves glycemic control as monotherapy and in combination with other oral antidiabetic agents, such as sulfonylureas and thiazolidinediones (Frendell et al. 2003). Several plant extracts are known to have antidiabetic properties and a large number of compounds from plant extracts have been reported to have beneficial effects for treatment of diabetes mellitus (Anhauser, 2003). Tea (Camellia sinensis L.) is one of plant that can decrease blood glucose. Green tea is produced by enzymatic inactivation of the leaves of Camellia sinensis followed by rolling or comminution and drying. In the manufacturer of green tea, the enzymatic inactivation achieved by steam or pan firing treatment to preserve natural polyphenols with respect to the health promoting properties. Green tea derived products are mainly extracts of green tea in liquid or powder form varying in the proportion of polyphenols (45-90%) and caffeine content (0.4-10%). The polyphenolic fraction of green tea, has been reported to have multiple pharmacological actions (Sano et al., 1995). Green tea is an excellent source of polyphenol antioxidants, known as green tea catechins. The important catechins of green tea are epicatechin (EC), epicatechin-3-gallate (ECG), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG). The polyphenolic fractions of green tea have been reported to have multiple pharmacological actions. They exhibit potent antioxidant activity in vitro and in vivo. Epidemiologic observation and laboratory studies have indicated that polyphenolic compounds present in the tea may reduce the risk of a variety of illnesses, including cancer and coronary heart disease (McKay and Blumberg 2002). Some studies suggest that green tea extract lowered cholesterol levels and blood glucose on mice and rat (Yang et al., 2001). Green tea extract at dose of 300mg /kg /day can lower blood glucose in diabetic rats and was also able to reduce the lipids in heart defects (Babu et al., 2006). Blood glucose lowering activity of green tea was greater and total polyphenol content was higher when compared with black tea and oolong tea (Holidah et al., 2015). METHODS Animal Adult male Balb/C mice (20-30 g and 2-3 month age) were kept in mice cages at room temperature (27 ± 2 0 C) and humidity (55 ± 5%) and a 12 hours cycle of light and dark. The mice were acclamatized for two weeks prior to commencement of the experiment and supplied with standard pellet food with tap water ad libitum. Chemical