In recent old ages, more so 100 medicative workss are mentioned in the Indian system of medical specialty including common people medical specialties for the direction of diabetes, which are effectual either individually or in combination3. We have under taken a survey on combination of works and doing a preparation so measuring its anti hyperglycemic belongings along with its antioxidant potency.
Preliminary phytochemical analysis of ethanolic infusion of rootstocks of Picrorhiza scrophulariiflora ( EEPS ) shown the presence of phytochemicals such as glycosides, alkaloids, polysterols, saccharides, proteins, phenols, tannic acids, saponins, and steroid alcohols etc. ,
Acute unwritten toxicity survey of EEPS did non exhibit mortality or any profound toxic reactions at a dosage of 2000mg/kg/p.o. Harmonizing to the ( OECD ) 423 guidelines for acute unwritten toxicity survey LD50, dosage of 2000mg/kg/p.o of PHF is found to be safe.
The EEPS at a dose 250mg/kg/p.o and 500mg/kg/p.o did non significantly suppress blood glucose degree in over dark fasted normal animate beings after 1st,2nd and 3rd hours of unwritten disposal when compared with standard drug like biguanide categories of drugs such as Glucophage which is anti-hyperglycemic drug. They do non impact blood glucose in normal individuals.68
The EEPS showed important betterment in glucose tolerance in glucose fed hyperglycemic normal rats. Such an consequence may be accounted for, in portion, by a lessening in the rate of enteric glucose soaking up, achieved by an excess pancreatic action including the stimulation of peripheral glucose use or heightening glycolytic and glycogenic process62. However the consequence was important when compared to standard drug glibenclamide and Glucophage.
STZ is the most normally used drug for the initiation of experimental diabetes for both insulin -dependent diabetes mellitus and non-insulin dependant diabetes mellitus. Type II diabetes diabetes is associated with fleshiness, and fleshiness itself causes or aggravates insulin opposition which is found to be a major cause of type II diabetes. There is an increasing grounds that streptozotocin causes diabetes by rapid depletion of ?-cells, by DNA alkylation and accretion of cytotoxic free groups that is suggested to ensue from initial islet redness. It leads to a decrease in insulin release at that place by a drastic decrease in plasma insulin concentration taking to stable hyperglycemic state69. In this survey important hyperglycaemia was achieved within 48 hours after streptozotocin ( 35mg/kg b.w i.p ) injection. Streptozotocin induced diabetic rats with more than 250mg/dl of blood glucose were considered to be diabetic and used for survey.
A individual dose disposal of EEPS at a dose 250mg/kg/p.o and 500mg/kg/p.o significantly reduced the blood glucose degrees at 120 and 240min. In the sub-acute survey, glibenclamide intervention reduces blood sugar degree from the first hebdomad to 3rd hebdomad. Treatment with EEPS at dose 250mg / K g biological warfare / p.o significantly ( P & A ; lt ; 0.05 ) decreased the blood glucose degree after 2nd hebdomad. Treatment with EEPS at dose 500mg/kg/p.o significantly ( P & A ; lt ; 0.01 ) decreased the blood glucose degree after first hebdomad. At the terminal of the survey a pronounced anti hyperglycemic consequence was observed with the EEPS intervention. The possible mechanism involved in stamp downing of blood glucose degrees by EEPS are transition glucose conveyance, glucose disposal, secretagogue insulin secretion69 and which in bend to command the hyper glycemic state70.
Histopathological surveies showed outstanding islet cell hyperplasia and regeneration of islet cells show a cogent evidence for possible anti-hyperglycemic belongings of the EEPS.
Eperimental initiation of diabetes with High fat-fed diet with low dosage of STZ is associated with the characteristic loss of organic structure weight which is due to increased musculus cachexia and due to loss of tissue protein. Diabetic rats treated with EEPS show an addition in the organic structure weight every bit compared to the diabetic control which may be due to its protective consequence in commanding musculus blowing i.e reversal of gluconeogenesis and may besides be to the betterment in insulin secernment and glycemic control71.
Glycated heamoglobin is formed throughout the circulative life of RBC with the add-on of glucose to the N-terminal of the haemoglobin beta concatenation. This procedure which is nonenzymatic reflects the mean exposure of haemoglobin to glucose to an drawn-out period. Glycoheamoglobin is used as an index of metabolic control of diabetes72. In the present survey, High fat-fed diet with STZ treated distinct abnormalcies in the HbA1C degrees were apparent from elevated degree of normal glycated heamoglobin. EEPS at the dosage of 500mg/kg intervention over 21days significantly reduced the HbA1C degrees compared to the diabetic control.
In diabetes hyperlipidimea is found to be pathological province, in which elevated serum entire cholesterin and decreased serum HDL cholesterin addition diabetic complications by speed uping cell decease and coronary artery disease. In present survey, intervention with EEPS at dose 250mg/kg and 500mg/kg significantly ( p & A ; lt ; 0.01 ) , decrease sum cholesterin and significantly increase HDL degrees. This consequence non merely due to better glycemic control but could besides been due to that drugs direct action on lipid metabolic tract. Hypolipidemic consequence could stand for a protective mechanism against the development of atheroscclerisis73. Lipid take downing activity of EEPS at the dosage of 500mg/kg related to acitivty of standard drug Glucophage.
Elevated production of Reactive Oxygen Species ROS leads to cell harm. High degree of ROS has been found to play major function in the pathogenisis of type II diabetes. In this signifier of diabetes hypo-insulinaemia additions the activity of the enzyme, fatty acyl coenzyme A oxidase and initiates ?-oxidation of fatty acid that favors to roll up free groups ensuing in Lipid peroxidation. Increased concentration of lipid peroxidation in the liver impairs membrane maps by diminishing membrane fluidness and altering the activity of membrane-bound enzyme and receptor. Its end merchandise ( lipid group and lipid peroxide ) are harmful to the cells in the organic structure and associated with atherosclerosis57.
An addition in the degree of MDA concentration in High fat-fed diet with STZ induced type II diabetic rats57. In the present survey MDA and hydrogen peroxide degrees in liver were high in diabetic animate beings. The intervention with EEPS, glibenclamide and Glucophage exerted aprotective against peroxidative harm.
The enzymatic antioxidant defence mechanism contains assorted signifiers of SOD, catalase, glutathione peroxidase, glutathione reducatse and glutathione s transferases. Despite the presence of such a delicate cellular antioxidant systems an over production of ROS in both intra and extracellular infinites frequently occur exposure of cells to certain chemicals like STZ that output to the pathogenisis of DM in experimental animate beings. In the present survey we have examined the oxidatvioe emphasis tract marker in STZ induced diabetes rats. SOD and catalase are the most of import enzymes that scavenge the toxic free groups and organize the major anti oxidizer system. SOD protects the tissues against O free groups by catalysing the remotion of superoxide groups ( O2. ) into H2O2 plus O2 at that place by decreasing the toxic effects of the free groups. Catalase is a heme protein localized in the peroxyzomes or the micro peroxyzomes it is a major determiner of hepatic anti oxidant position. It catalyse the decomposition of H peroxide to H2O and O therefore protecting the cell from the oxidative damage74. Super oxide dismutase and catalase activity in the in the diabetic control animate beings was significantly low due to oxidative strees when compared to the normal animate beings. Treatment with EEPS at a dose 250mg/kg and 500mg/kg a significantly ( p & A ; lt ; 0.050 and ( P & A ; lt ; 0.01 ) , glibenclamide and Glucophage treated animate beings addition in the enzyme activity. EEPS at dosage of 500mg/kg exhibit pharmacological response related to Glucophages.
The decrease of H peroxide is catalysed by glutathione peroxidase into H2O and O at the disbursal of GSH. GPx activity is besides reduced in diabetic status. This may be due to inactivation of the enzyme involved in disposal of O2 species and besides deficient handiness of GSH75. Glutatathione peroxidase activity in the diabetic control animate being was significantly low due to increased oxidative emphasis when compared to the normal animate beings. Treatment with EEPS at a dose 250mg/kg and 500mg/kg a important ( p & A ; lt ; 0.050 and ( P & A ; lt ; 0.01 ) addition in the hepatic glutathione peroxidase antioxidant enzyme degrees.