ABSTRACT:

Diabetes mellitus is a world’s largest endocrine disease involving metabolic disorders of carbohydrate, protein and fat. This study was undertaken to investigate the anti-diabetic activity of corilagin, a member of polyphenolic tannins used against hyperglycemia and many other diseases in well-known animal models. Diabetes was induced chemically by intraperitoneal administration of Streptozotocin (40 mg/kg bw) to albino Wistar rats, which showed significant increase in the levels of fasting blood glucose, glycated haemoglobin, total cholesterol, triglyceride, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, and a significant decrease in the level of body weight, plasma insulin, high density lipoprotein cholesterol, antioxidant activities, viz. superoxide dismutase, catalase and reduced glutathione. However, after 30 days of oral administration of corilagin (10and 20 mg/kg bw/day) to these diabetic rats evoked significant alterations in the above mentioned parameters. The efficacy of corilagin was compared with the standard glibenclamide (0.1 mg/kg body weight/day). Thus, our study demonstrates that corilagin has a potential to regulate diabetes, by exhibiting antidiabetic, antihyperlipidemic and antioxidant properties in STZ induced diabetic rats.

Keywords

Corilagin; streptozotocin; glibenclamide; antidiabetic; antihyperlipidemic; antioxidant

1. Introduction

The world’s largest endocrine disease involving metabolic disorders is diabetes mellitus (DM) (Chaiyasut et al. 2011). DM is characterized by hyperglycemia due to relative or absolute deficiencies in insulin action or insulin secretion. DM is considered a “modern day epidemic” and is recognized as a global public health issue due to its substantial financial burden worldwide on the healthcare system and its negative impact on the quality of life. Over the last century, there is a dramatic increase in the incidence of diabetes resulted from obesity, sedentary lifestyle and consumption of calorie rich diets (Souto et al. 2011). According to International Diabetes Federation (IDF), 382 million people (8.3%) suffer from DM and the estimation of this illness is projected to increase more than 592 million by 2035 worldwide (IDF, 2014).

A large body of evidence suggests that inability of pancreatic β-cells to produce a physiologically appropriate amount of insulin leads to a chronic hyperglycemic condition in DM. The chronic hyperglycemia of diabetes generates auto oxidation of glucose and auto oxidative glycosylation of proteins which leads to oxidative stress by increasing the reactive oxygen species (ROS) (King and Loken, 2004). ROS contribute to the development of diabetic complications including tissue damage, heart and peripheral vascular complaints, retinopathy, nephropathy and neuropathy (Wiernsperger, 2003).

Drug prescription remains to be the major successful approach to improve diabetic condition, despite lifestyle modification as the first-line approach for an early stage of diabetes. Currently, different types of oral hypoglycemic agents are available along with insulin for the

treatment of DM. But these products possess adverse effects which include hypoglycemia, hepatotoxicity, dyslipidemia and attenuation of response after protracted use (Tahrani et al. 2011). In consequence, there is a need for the search of new therapeutic agents. Medicinal plants have always been rich sources of biologically active compounds vital to human health. Some plant-derived bioactive compounds, including epicatechin (Chakravarthy et al. 1982), quercetin (Shisheva and Shechter, 1992), pueranin (Hsu et al. 2003), kaempferol (De-Sousa et al. 2004), hesperidin (El-Alfy et al. 2005), proanthocyanidins and genistinin (Lee, 2006), are also known to regulate hyperglycaemia. Corilagin (Figure 1) (Schmidt and Lademann, 1951) is a member of polyphenolic tannins, has been discovered in a number of medicinal plants such as Punicagranatum(Guo et al. 2017),Terminaliachebula(Grover and Bala, 1992),Rosarugosa,Eugeniacaryophyllata,Punicagranatum(Li et al. 2014),Phyllanthusniruri(Jia et al. 2013),Emblicaofficinalis(Khan, 2009),DimocarpusLongan,Phyllanthusurinaria(Zheng et al. 2016), Syzygiumcumini(Chauhan and Intelli, 2015).Recent studies have shown that corilagin exhibit health benefits including antioxidant (Kinoshita et al. 2007), antihypertensive (Cheng, 1995), antiapoptotic and hepatoprotective effects (Hau, 2009). Corilagin also exhibit protective action against herpes simplex virus (HSV) 1 encephalitis (Guo et al. 2010). A previous study has shown that corilagin is protective against GalN/LPS-induced liver injury through suppression of oxidative stress and apoptosis (Kinoshita et al. 2007), and act as an inhibitor of TNF-α (Okabe et al. 2001). Furthermore, NF-κB activation also inhibited by corilagin (Gambari et al. 2012). The latest research reported that damage caused by cigarette smoke on lung epithelial cells could be attenuated by corilagin (Muresan et al. 2015). Although, there is an association exists between hyperglycemia  and  corilagin  (Honma  et  al.  2010),  there  is  no  systematic  investigation  is

available on anti-diabetic activity of corilagin. Therefore, the present work was carried out to evaluate the efficacy of corilagin in regulating DM.

Figure1:Strcture of corilagin.

2. Materials and methods

1. Materials

Corilagin (≥95%) and STZ were purchased from Sigma- Aldrich (St. Louis, MO). For the biochemical assessments, the diagnostic kits were supplied from Swemed Biomedicals Pvt. Ltd.

(Bengaluru, India). All the other chemicals used in the present study are of analytical grade obtained from standard commercial suppliers.

2. Maintenance of animals

Healthy adult albino Wistar rats were used in the current study, weighing 180–210 g was acquired from Central Animal House, Department of studies in Zoology, University of Mysore. The animals were housed in standard polypropylene cages and maintained in an air-conditioned room (25 ± 10C) with a 12-h light/12-h dark cycle and were fed a standard diet of known composition, and water adlibitum.Animal experiments were performed in accordance with regulations specified and monitored by the Institutional Ethics Committee of University of Mysore (Approval number – UOM/IAEC/18/2012) and followed the guidelines of Committee for the Purpose of Control and Supervision of Experiments on Animals.

3. Induction of experimental diabetes

Streptozotocin (STZ) was freshly dissolved in (0.01 M, pH 4.5) citrate buffer. DM was induced in overnight fasted rats by a single intraperitoneal injection of STZ (40 mg/kg b.w.), and the injection volume was 1 ml/rat. Control animals were injected with citrate buffer alone. After 72h of STZ injection, diabetes was confirmed by measuring the fasting blood glucose (FBG) concentration. The animals with FBG values above 235 mg/dL were considered to be diabetic and included in the present study (Prisilla et al. 2012).

4. Experimental design

Rats (n=25) were randomized into the following groups after the induction of STZ diabetes:

Group I: Control

Group II: Diabetic Control

Group III: Diabetic + Glibenclamide (0.1 mg/kg body weight/day) Group IV: Diabetic + Corilagin (10 mg/kg body weight/day) Group V: Diabetic + Corilagin (20 mg/kg body weight/day)

Corilagin and glibenclamide were diluted in water and administered via oral intubation daily for a period of one month. The initial and final body weights of each rat in various groups were recorded. At the end of the experimental period, all the animals were fasted overnight, and sacrificed under mild ether anesthesia.

Blood samples were collected from the carotid artery and centrifuged at 1000 rpm for 10 min, and the serum was obtained and used for various biochemical estimations.

5. Analytical procedure

1. Fasting blood glucose (FBG)

At weekly intervals, blood samples were withdrawn by nicking the tip of the rat tail and the FBG level was estimated using glucometer (Accu-Chek, Mannheim, Germany) in which its principle is based on the glucose oxidase method. Results were expressed as mg/dL.

2. Plasma insulin and glycated hemoglobin (HbA1c)

Plasma insulin was estimated using a commercial ELISA kit purchased from DRG diagnostics (GmbH, Germany). HbA1c in whole blood was measured using commercial assay kit following the protocol provided by manufacturer (Swemed Biomedicals, Pvt. Ltd., Bengaluru, India).

3. Measurement of Serum Lipid Profile

Serum concentrations of triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were determined through Artos –Versatile Clinical Chemistry Analyzer using commercially available kits (supplied by Swemed Biomedicals, Pvt. Ltd., Bengaluru, India). Low-density lipoprotein cholesterol (LDL-C) and very  low-density lipoprotein cholesterol (VLDL-C) were calculated according to Friedewald’s formula LDL = [(TC − HDL) − TG/5] and VLDL cholesterol =TG/5 (Friedewald et al. 1972).

6.                        Measurements of antioxidant activity

1.    Assay of Superoxide dismutase (SOD)

Inhibition of superoxide driven oxidation of quercetin by SOD at 406 nm was measured in this assay. The complete reaction mixture consisted of 25 mM phosphate buffer (pH 7.8), 0.25 mM EDTA, 0.8 mM TEMED and 0.05 μM quercetin. The amount of enzyme that inhibits the auto-oxidation of quercetin by 50% was defined as one unit (Kostyuk and Potapovich, 1989).

2.    Assay of Catalase (CAT)

CAT activity was estimated by Aebi method (1984), following the clearance of H2O2 at 240 nm in a reaction media containing 50 mM phosphate buffer (pH 7.0), 0.5 mM EDTA, 10 mM H2O2, 0.012 %TRITONX100. Activity was expressed as µmol H2O2 (HP) decomposed/min/mg protein.

3.    Assay of reduced glutathione (GSH)

Samples were taken in 96-well microtiter plates. The final volume was made up to 100

µL with 100 mM phosphate buffer (pH 8.0, containing 5 mM EDTA), and 25 µL O- phthalaldehyde was added and incubated for 45 min at 37° C. After exciting the samples at 340 nm, fluorescence emission was recorded at 425 nm and the GSH was calculated (Hissin and Hilf, 1976).

2.7. Statistical analysis

Data were analyzed by one way analysis of variance followed by Duncan’s multiple range test using SPSS software package, version 14 (Chicago, IL). Results were expressed as the mean ± SE. The P-value <0.05 was taken as indicating statistical significance.

3. Results

Table1.Effectofcorilaginonbodyweightinstreptozotocin-induceddiabeticWistarrats.

Note: All the values are represented in mean ± SEM.

Mean values with same superscript letters in the given column are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

1. Effect of corilagin on Fasting blood glucose (FBG)

In different groups of rats FBG (Figure 2) was monitored. FBG level of diabetic control rats were significantly higher when compared with normal control rats at the end of the experimental period. Diabetic rats when treated orally with corilagin resulted in reduced FBG level when compared to diabetic control rats at the end of the study. Corilagin at the dose of 20

mg/kg.bw decreased the FBG level in a way similar to that of the reference drug, glibenclamide. Although the treatment with corilagin at a dose of 10mg/kg.bw significantly reduced the FBG level, the decrease was not comparable to that of the reference drug.

Figure2:Effect of corilagin on fasting blood glucose concentration at weekly intervals (4 weeks) in streptozotocin-induced diabetic rats. All the values are represented in mean ± SEM.

2. Effect of corilagin on Plasma insulin and glycated hemoglobin (HbA1c)

The effect of corilagin on the levels of plasma insulin and HbA1c in STZ-induced diabetic rats is shown in Figure 3 and 4. Plasma insulin level was significantly decreased in

diabetic rats as compared with normal control rats. Oral administration of corilagin (10 mg/kg.bw and 20mg/kg.bw) to diabetic rats significantly improved the altered level; Corilagin dose 20 mg/kg.bw seemed to be more effective than corilagin dose 10mg/kg.bw. HbA1c, on the other hand, exhibited an opposite response pattern; it was significantly elevated in diabetic rats as compared to normal ones and was significantly decreased as the result of treatment with corilagin (10 mg/kg.bw and 20mg/kg.bw). Corilagin dose 20 mg/kg.bw seemed to be more effective on elevated HbA1c.

Figure3:Effect of corilagin on insulin in streptozotocin-induced diabetic rats. C, control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph  are not significantly

different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure4:Effect of corilagin on glycated haemoglobin in streptozotocin-induced diabetic rats. C, control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

3. Effect of corilagin on serum lipid profile

Data on the effect of corilagin on lipid profile of diabetic rats are presented in Table 2.Diabetic rats characterized by a significant increase in TG, TC, LDL-C and VLDL-C levels and a significant decrease in HDL-C level as compared with the non-diabetic group. On the other hand, all groups of STZ induced diabetic rats treated with corilagin 10 and 20 mg/kg.bw and glibenclamide, these markers were brought towards near normal level. These results indicate that corilagin 20 mg/kg.bw can effectively ameliorate of all parameters of the altered lipid profile.

Table 2. Effect of corilagin on lipid profile in streptozotocin-induced diabetic Wistar rats.

Note: All the values are represented in mean ± SEM.

Mean values with same superscript letters in the given column are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

4. Effect of corilagin on antioxidant status

The changes in the activities of SOD (Fig. 5and 6), CAT (Fig. 7 and 8), and GSH (Fig.9 and 10) level in the liver and kidney of diabetic and corilagin treated rats were measured. STZ diabetic rats were found to have decreased SOD, CAT activity and GSH level in the liver and kidney compared with control rats. Treatment of corilagin 10 and 20 mg/kg.bw and glibenclamide to diabetic animals produced a significant increase in SOD, CAT activity and GSH level. Corilagin at 20 mg/kg.bw was more effective than 10 mg/kg.bw in antioxidant parameters.

Figure5:Effect of corilagin on the activitity of SOD of liver in streptozotocin-induced diabetic rats. C, control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given

graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure6:Effect of corilagin on the activitity of SOD of kidney in streptozotocin-induced diabetic rats. C, control; VC, vehicle control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure7:Effect of corilagin on the activitity of CAT of liver in streptozotocin-induced diabetic rats. C, control; VC, vehicle control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure8:Effect of corilagin on the activitity of CAT of kidney in streptozotocin-induced diabetic rats. C, control; VC, vehicle control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure9:Effect of corilagin on GSH level of liver in streptozotocin-induced diabetic rats. C, control; VC, vehicle control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure10:Effect of corilagin on GSH level of kidney in streptozotocin-induced diabetic rats. C, control; VC, vehicle control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

4. Discussion

In the present study, the possible therapeutic effect of corilagin on STZ-induced diabetic rats was evaluated through carbohydrate metabolism, lipid metabolism and antioxidant status. Rats treated with STZ showed development of hyperglycemia and its complications. The cytotoxic action of STZ is mediated by the oxidative stress that can cause rapid destruction of β- cells of the pancreas by single- strand breaks in DNA. This ultimately leads to the partial loss of

insulin production, which paves the way for the decreased utilization of glucose by the tissues (Suthagar et al. 2009).

Insulin regulates the carbohydrate metabolizing enzymes in order to maintain glucose homeostasis. Elevation in FBG level may be due to the impairment in insulin secretion with reduced entry of glucose to peripheral tissues, muscle and adipose tissue (Beck-Nielsen, 2002), increased glycogen breakdown, increased gluconeogenesis and hepatic glucose production (Raju et al. 2001). The present data indicated a marked increase in FBG level in diabetic animals as compared to normal rats. Treatment with corilagin (10 and 20 mg/kg b.w. /day) significantly reduced the elevated FBG levels in STZ-induced diabetic rats. This could be due to the alteration of insulin metabolism, stimulation of glucose uptake by peripheral tissues and inhibition of glucose reabsorption by the kidneys (Roselino et al. 2012).It was also supported by a significant increase in body weight in treated rats compared to STZ-induced diabetic rats. The characteristic loss of body weight in the diabetic group may be because of protein wasting due to the inaccessibility of carbohydrates for energy metabolism and the degradation of structural proteins (Ramesh and Pugalendi, 2005). Oral administration of corilagin and glibenclamide ameliorates the hyperglycemia which in turn promotes the body weight gain by reversing gluconeogenesis in STZ-induced diabetic rats. The decrease in elevated FBG level and increase in body weight gain is in agreement with the results of Ramesh and Pugalendi (2006). This antihyperglycemic activity was further supported by the significant recovery in plasma insulin level in corilagin treated rats compared to diabetic rats. The possible mechanism by which corilagin (10 and 20 mg/kg b.w./day) increases plasma insulin level may be through potentiating the pancreatic secretion of insulin from existing β-cells of islets as previously reported by Han et al. 2014.

Further hyperglycemia, a hallmark of DM, leads to increase in the levels of HbA1c. Excess of glucose present in blood reacts with hemoglobin to form HbA1c in diabetes. The level of blood glucose is directly proportional to the amount of increase in HbA1c (Subash Babu et al. 2007). So the estimation of HbA1c has been found very useful to monitor the effectiveness of therapy in diabetes. Corilagin and glibenclamide administration decreased the elevation  of HbA1c in diabetic rats may be due to improved glycemic control by corilagin. Our results harmonized with the previous study reported using lycopene, a dietary pigment, which improved HbA1c by decreasing blood glucose level in diabetic rats (Ozmutlu et al. 2012).

A plethora of studies reported that profound alterations in lipid profile play a significant role in the development of diabetes and its complications (Aissaoui et al. 2011; Li et al. 2012). In addition, Keenoy et al. (2005) and Ravi et al. (2005) showed that the abnormalities in lipid metabolism generally led to elevation in the levels of serum lipids and lipoproteins. Insulin also plays an important role in the metabolism of lipids, apart from the regulation of carbohydrate metabolism. In diabetic animals rise in TG, TC, VLDL, LDL-C and fall in HDL-C is due to increased lipolysis in adipose tissue, and decreased activity of insulin dependent lipoprotein lipase leading to elevated level of fatty acids (Kavitha et al. 2016). Increased fatty acids concentration also increases the β-oxidation of fatty acids, producing more acetyl-CoA and cholesterol causes hypercholesterolemia, and further fatty acids are available for the synthesis of TG causes hypertriglyceridemia (Agardh et al. 1999). Glucose oxidation competitively inhibited by oxidation of TG, and thus reduces uptake and utilization of glucose in skeletal muscles and leads to insulin resistance. Under normal conditions, insulin increases the receptor-mediated removal  of  cholesterol,  and  it  also  activates  insulin  dependent  lipoprotein  lipase  which

hydrolyzes TG (Taskinen et al. 1986). During diabetes, enhanced lipolysis also increases the release of glycerol and hence increases the synthesis of phospholipids. Thus, the levels of lipids were altered, and these lipid abnormalities impair insulin secretion and action leading to β-cell failure in diabetic rats (Guo et al. 2017). In this study, elevation in FBG was accompanied by a marked increase in TC, TG, LDL-C, and VLDL in diabetic rats. On the other hand, a different pattern was shown by HDL-C, which was lowered detectably in diabetic rats. Treatment with corilagin produced profound improvements of the altered serum lipid variables in diabetic rats.

These results are consistent with previous reports (Ghatak and Panchal, 2012; Guo et al. 2017) that treated diabetic rats exhibit significantly decreased serum levels of TC, TG, LDL-C, VLDL and significantly increased HDL-C level. Hence, in diabetic rats corilagin may directly or indirectly influence on various lipid regulation systems.

The considered unifying factor in the development of diabetes complications is oxidative stress. Changes in oxidative stress occur due to either steaming from glucose mediated increase in free radical generation and/or reduction of endogenous antioxidant defense. These are the two strong contenders for the title of root cause of diabetic complications. Lipid peroxidation causes membrane and tissue damage due to overproduction of free radicals in diabetic animals. (Gaona- Gaona et al. 2011). Therefore during the treatment of diabetes, regulation of damaging ROS by antioxidants and free radical scavengers represents an attractive benefit. The cellular antioxidants SOD, CAT, GSH are known to protect against ROS such as O−, OH− and H2O2. Since superoxide dismutase and catalase involved in the direct elimination of ROS, they are considered as primary enzymes. The SOD catalyzes the dismutation of superoxide radicals (McCord et al. 1976), and  a  hemoprotein  CAT  protects  tissues from  highly  reactive  hydroxyl  radicals  by

catalyzing the reduction of H2O2 (Chance et al. 1952). Another antioxidant, GSH detoxifies H2O2 to H2O through the oxidation of reduced glutathione and helps to regulate the internal redox environment  of  cells  (Bruce  et  al.  1982).  Thus,  lipid  peroxidation  is  counteracted  by  the

antioxidants such as SOD, CAT and GSH. A significant decrease in the SOD and CAT activities and GSH level, observed in the tissues of diabetic rats, has been shown to be a significant adaptive response to increased oxidative stress (Matcovis et al. 1982). In our study, corilagin treatment of diabetic rats was observed to significantly recover decreased activities of the SOD and CAT with augmented GSH level. The obtained data in the present study confirm the amelioration of oxidative stress in the STZ diabetic rats. These results are compatible with the findings reported by Li et al. (2014); Ahad et al. (2014) which restrains oxidative damage in STZ-induced diabetic rats.

In conclusion, the present study indicates that the corilagin treatment ameliorates hyperglycemia, hyperlipidemia, and oxidative stress in diabetic rats. The antidiabetic activity of this compound could be because of enhanced peripheral glucose utilization by skeletal muscle in addition to that of β-cell stimulation. However, these findings are encouraging for further studies on the structure activity relationship and its mode of action. Our study provides comprehensive insights for the discovery of safer and beneficial therapeutics.

5. Data availability

All the data and materials supporting the conclusions were included in the main paper.

Declarations of interest:

None.

Funding sources:

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgement:

The authors thank for all lab members.

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Legends:

Figure1:Strcture of corilagin.

Figure2:Effect of corilagin on fasting blood glucose concentration at weekly intervals (4  weeks) in streptozotocin-induced diabetic rats. All the values are represented in mean ± SEM.

Figure3:Effect of corilagin on insulin in streptozotocin-induced diabetic rats. C, control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure4:Effect of corilagin on glycated haemoglobin in streptozotocin-induced diabetic rats. C, control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure5:Effect of corilagin on the activitity of SOD of liver in streptozotocin-induced diabetic rats. C, control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure6:Effect of corilagin on the activitity of SOD of kidney in streptozotocin-induced diabetic rats. C, control; VC, vehicle control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure7:Effect of corilagin on the activitity of CAT of liver in streptozotocin-induced diabetic rats. C, control; VC, vehicle control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure8:Effect of corilagin on the activitity of CAT of kidney in streptozotocin-induced diabetic rats. C, control; VC, vehicle control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure9:Effect of corilagin on GSH level of liver in streptozotocin-induced diabetic rats. C, control; VC, vehicle control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the

given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Figure10:Effect of corilagin on GSH level of kidney in streptozotocin-induced diabetic rats. C, control; VC, vehicle control; DC, diabetic control; D,diabetic; GB,glibenclamide; CO, corilagin. All the values are represented in mean ± SEM. Mean values with same superscript letters in the given graph are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

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Table 1. Effect of corilagin on body weight in streptozotocin-induced diabetic Wistar rats.

Body weight (g)

Groups Initial Final

Note: All the values are represented in mean ± SEM.

Mean values with same superscript letters in the given column are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.

Table 2. Effect of corilagin on lipid profile in streptozotocin-induced diabetic Wistar rats.

Note: All the values are represented in mean ± SEM.

Mean values with same superscript letters in the given column are not significantly different, whereas those with different superscript letters are significantly different (p<0.05) as judged by DMRT.