History suggests that diabetes and cardiovascular diseases were present in ancient civilisations. Physicians in Ancient Egypt described the diabetes-like syndrome about 3,500 old ages ago in Ebers papyrus, found in a grave in Thebes part in the South of Egypt in 1862 ( Ahmed, 2002 ) . Sushrant, an Indian doctor, described diabetes as polyuric wastage diseases in literature from the 5th-6th century AD ( Ahmed, 2002 ) . The term “ diabetes ” was foremost coined by Arataeus the Cappodocian ( about 81-133AD ) , intending “ a syphon ” . Thomas Willis ( Britain ) in 1675 added another word “ mellitus ” intending “ honey-like Sweet ” ( Ahmed, 2002 ) . The Iranian doctor, Ibn Sina ( 980-1037 ) , known as Avicenna in Western Europe, described some of the clinical characteristics and complications of diabetes such as peripheral neuropathy, sphacelus and erectile disfunction ( Iskeandar, 1986 ) .
Diabetess can be described as disfunction of the pancreatic i??-cell endocrine, insulin. The most common signifier of diabetes involves the development of insulin opposition where insulin loses its effectivity to increase glucose uptake into cells, particularly in skeletal musculus and liver. This signifier of diabetes, known as type 2 diabetes, frequently occurs in patients with high blood pressure and fleshiness ; this bunch of symptoms is now known as the metabolic syndrome ( Huang, 2009 ) , once as syndrome X ( Reaven, 1988 ) . The clinical definition of the metabolic syndrome was foremost reported by Alberti & A ; Zimmer ( 1998 ) with the indispensable demands being insulin opposition together with any two of the following four standards: fleshiness, dyslipidaemia, high blood pressure and microalbuminuria ( Alberti and Zimmer 1998 ) . Diagnostic standards were refined in 1999 by the European Group for the Study of Insulin Resistance ( EGIR ) , in 2001 by the National Cholesterol Education Program ( NCEP ) Adult Treatment Panel III ( ATP III ) updated in 2005 by American Heart Association and the National Heart Lung and Blood Institute and in 2005 by the International Diabetes Foundation ( IDF ) ( Alberti et al. , 2006 ) . All the definitions required increased plasma glucose concentrations together with high blood pressure, dyslipidaemia and cardinal fleshiness. These symptoms do non to the full specify the syndrome as the socioeconomic background, life manner, household history, age, sex and environmental factors are seldom considered.
Harmonizing to the American Heart Association study, metabolic syndrome and cardiovascular disease are the prima causes of morbidity and mortality of patients in USA and besides in the developed universe ( Bleich et al. , 2008 ; Lloyd-Jones et al. , 2010 ) . The figure of patients is besides increasing in developing states such as India, China, Latin America and Eastern Europe ( Hossain et al. , 2007, Mishra and Khurana, 2008 ) . Major well-known hazard factors of cardiovascular disease include a household history of premature coronary disease, high blood pressure, elevated concentrations of low-density lipoprotein cholesterin ( LDL-C ) , lipemia, smoke and type-2 diabetes. Clinical features of cardiovascular disease include myocardial infarction, coronary arteria disease, shot, peripheral arteria disease and congestive bosom failure. The Framingham Heart Study revealed that high blood pressure, diabetes and left ventricular remodelling lead to the development of congestive bosom failure ( Armstrong 2000 ) . The Framingham Heart Study besides found that a 5 % addition in weight additions the opportunity of high blood pressure by 30 % over a four-year period of clip. An increased sympathetic activity, impaired renin-angiotensin system, keeping of fluid volume, peripheral vasoconstriction, dyslipidaemia, increased blood viscousness due to the increased hematocrit and factor I may increase force per unit area overload on bosom in fleshiness ( Schunkert, 2002 ) . Recently, inflammatory signalling mechanisms and an overrun of reactive O species have been good documented in cardiovascular upset and diabetes ( du Toit et al. , 2005 ; Rodford et al. , 2008 ; Renna et al. , 2009 ; Yamaguchi et al. , 2009 ) .
1.2 Oxidative emphasis
Oxidative emphasis can be defined as the cellular harm caused by extra formation of extremely reactive molecules such as reactive O species ( ROS ) and reactive N species or an deficient remotion of ROS due to the deficiency of antioxidative enzymes including superoxide dismutase, catalase and preoxidase or both ( Turko et al. , 2003 ; Johansen et al. , 2005 ) . ROS include free groups such as superoxide ( aˆ?O2- ) , hydroxyl ( aˆ?OH ) every bit good as nonradical species such as H peroxide ( H2O2 ) and hypochlorous acid ( HOCl ) etc. ( Evans et al. , 2002 ; Johansen et al. , 2005 ) . The mitochondrial respiratory concatenation and NADPH oxidase household are the most of import beginnings of ROS in non-phagocytic cells including pancreatic islets ( Yu et al. , 2008 ; Nishikawa et al. , 2000 ; Uchizono et al. , 2006 ; Dworakowski et al. , 2006, Paravicini and Touyz, 2008 ) . The tissue harm caused by ROS in diabetes includes lipid peroxidation, inactivation of proteins and protein glycation as intermediate mechanisms ( Wolffe et al. , 1991 ) which may do complications including retinopathy, nephropathy and coronary bosom disease ( Makimattila et al. , 1999 ; Inoguchi et al. , 2003 ) .
1.3 Cardiac remodelling and hypertrophy
Cardiac remodelling is normally an adaptative procedure that occurs in response to long-run alterations in haemodynamic conditions such as volume overload or increased sheer emphasis, but it may later lend to the pathophysiology of vascular diseases and circulatory upsets. Therefore cardiac remodelling can be defined as a procedure of structural alterations in one or more cardiac Chamberss, in peculiar the ventricles. Cardiac remodelling is best described as molecular, cellular, interstitial and genomic alterations that are manifested clinically as changes in size, form and map of the bosom following cardiac hurt ( Feuerstein and Weck, 1999 ) . Epidemiologic surveies suggest that left ventricular remodelling is common in patients with metabolic syndrome ( Patel et al. , 2009 ) . Important go-betweens include haemodynamic burden, wall emphasis, neurohormonal activation ( sympathetic system, renin-angiotensin system, aldosterone and endothelin ) , cytokines, oxidative emphasis and ischemia.
1.4 Obesity, diabetes and cardiovascular remodelling
Fleshiness is considered as an independent hazard factor for developing cardiovascular upset and assorted grades of cardiac remodelling ( Avelar et al. , 2007, Abel et al. , 2008 ) . These alterations include hypertrophy of the bosom, left ventricular weight addition, interstitial fibrosis and collagen deposition, epicardial fat accretion and infiltration of lipoid in myocardium ( Avelar et al. , 2007, Abel et al. , 2008 ) . High saccharide, high fat eating caused fleshiness, left ventricular hypertrophy and remodelling in Wistar rats ( Panchal et al. , 2010 ) .
Insulin itself is another regulator of cardiac myocyte growing and energy metamorphosis. Clinical surveies have found that hypertensive patients with high plasma insulin concentrations have an increased incidence of left ventricular hypertrophy, proposing that insulin may trip pathological cardiac growing when the bosom is subjected to chronic force per unit area overload ( Shigematsu et al. , 2005 ; Rutter et al. , 2003 ; Stiefel et al. , 2004 ) .
Glucose auto-oxidation increases the ROS coevals through mitochondrial negatron conveyance concatenation during production of ATP. Accelerated flux of glucose through glycolysis and eating of pyruvate to the tricarboxylic acerb rhythm overloads chondriosomes, doing inordinate coevals of free groups at the degree of complex II ( succinate: ubiquinone oxidoreductase ) , one of the four interior membrane-associated composites cardinal to oxidative phosphorylation ( Nishikawa et al. , 2000 ) . Cross-talk between mitochondrial negatron conveyance concatenation ROS production and NAD ( P ) H oxidase system has been reported late ( Ceriello, 2003 ) . The activation of protein kinase C together with increased de novo synthesis of NAD ( P ) H oxidase contributes to bring forth more superoxide anions ( Hink et al. , 2001 ) .
Systemic high blood pressure induces chronic left ventricular force per unit area overload and is a recognized subscriber to bosom failure. Several surveies besides suggest that the cause of high blood pressure itself may lend to go forth ventricular hypertrophy in corpulent persons as the addition of BMI increases the opportunity of high blood pressure ( De Simone et al. , 1994 ; Avelar et al. , 2007 ) . High dietetic fat consumption increases the look of AT1B and ETA receptors ( Neilsen et al. , 2004 ; Zhang et al. , 2005 ) . Plasma concentrations of angiotonin II and endothelin 1 ( physiological vasoconstrictive agents ) were increased in both corpulent patients and carnal theoretical accounts ( Barton et al. , 2000 ; Neilsen et al. , 2004 ; Zhang et al. , 2005 ) . Mouse theoretical accounts deficient in ROS-forming enzymes have lower blood force per unit areas compared with wild-type opposite numbers and angiotonin II extract in these mice failed to bring on high blood pressure ( Bendall et al. , 2002 ; Li and Shah 2003 ) . Angiotensin II besides stimulated ROS coevals by triping the NADPH oxidase in endothelial system. PLD, PLA, PKC, c-Src, PI3 K, RhoA, and Rac 1, 2 proteins are believed to be involved in up-regulating signalling cascade for AT1 signalling to NAD ( P ) H oxidase ( Seshiah et al. , 2002 ; Touyz et al. , 2003 ) .
Significance of the survey
The usage of natural merchandises in handling diseases and unwellness has been recognized since antediluvian times. Public and scientific involvement in the usage of natural merchandises is considerable with the premise that they have notably less toxicity compared to man-made drug medicine to battle human diseases such as cardiovascular disease, malignant neoplastic disease and inflammatory diseases. Diabetess and cardiovascular diseases are going epidemic non-communicable diseases around the universe. This is making a load on the wellness sector of both developed and underdeveloped universe and slows down the growing of economic systems of these states. This economic load includes the productiveness lost and increasing cost for the direction and intervention of the diseases status. The International Diabetes Federation Diabetes Atlas ( 4th edition, 2009 study ) notes that planetary health care outgo to handle and forestall diabetes is International Dollars ( ID ) 418 billion in 2010 and is predicted to lift to 561 billion ID in 2030 ( Economic impacts of diabetes, Diabetes atlas, 2009 ) .
Australia is one of the most developed states where life anticipation is the 2nd highest in the universe after Japan ( about 81.4 old ages ) with cardiovascular diseases staying the major cause of decease ( Australian Institute of Health and Welfare, 2008 ) . Diabetes, fleshiness and cardiovascular diseases have been increasing in recent old ages, duplicating between 1988 and 2002. With an ripening and progressively corpulent population, the fiscal load of handling type II diabetes could quadruple by 2051 unless more is done to forestall or detain the disease and its complications ( Davis et al. , 2006 ) . The Australian Diabetes, fleshiness and life manner survey ( AUSDIAB ) predicted the alterations in glucose indices, wellness behavior and incidence of diabetes in 5 twelvemonth follow-up experiments among 5842 participants ( Barr et al. , 2007 ) . This survey suggested that a big figure of Australians suffer mortality due to cardiovascular diseases associated with unnatural glucose metamorphosis every twelvemonth. The undertakings reported in this thesis will find the structural and functional alterations in the cardiovascular system every bit good as in the liver and pancreas, every bit good as metabolic alterations due to oxidative emphasis and metabolic syndrome and so find the possible good functions of phenolic acids and natural antioxidants utilizing an appropriate rat theoretical account