Action of Corilagin on Hyperglycemia, Hyperlipidemia and Oxidative Damage in Streptozotocin-induced Diabetic Rats

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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.

  1. 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.

  1. 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.

  1. 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).

  1. 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.

  1. 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.

  1. 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).

  1. 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).

  1.                        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).

  1.    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.

  1.    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.

  1. Results

 

 

 

Table1.Effectofcorilaginonbodyweightinstreptozotocin-induceddiabeticWistarrats.

 

 

 

 

Groups

 

Body weight (g)

Initial Final
 

 

Control

 

 

187.4±1.54

 

 

214.2±1.37b

 

Diabetic Control

 

197.6±1.78

 

141±1.87a

 

Diabetic+Glibenclamide (0.1mg/kg body weight/day) Diabetic+corilagin (10 mg/kg body weight/day)

 

177.4±2.11

 

186±1.00

 

217.6±1.08b

 

210.8±3.15b

 

Diabetic+ corilagin (20 mg/kg body weight/day)

 

187.8±1.95

 

212.4±2.58b

 

 

 

 

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.

  1. 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.

  1. 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.

 

 

 

Groups Totalcholesterol(mg/dL) Triglycerides(mg/dL) HDLcholesterol

(mg/dL)

LDLcholesterol(mg/dL) VLDLcholesterol(mg/dL)
 

 

 

Control

 

 

 

100.53±0.67a

 

 

 

79.58±0.76a

 

 

 

51.48±0.94d

 

 

 

33.13±1.26a

 

 

 

15.91±0.15a

 

Diabetic Control

 

162.34±0.61e

 

165.87±1.51e

 

33.87±0.76a

 

95.3±1.00e

 

33.17±0.30e

 

 

Diabetic+Glibenclamide (0.1mg/kg body weight/day)

 

 

103.06±1.47b

 

 

81.10±0.85b

 

 

50.12±0.94cd

 

 

36.72±2.03b

 

 

16.22±0.17ab

 

Diabetic+corilagin

(10 mg/kg body weight/day) 108.53±1.74d 86.81±0.82d 47.09±0.41b 44.08±1.73d 17.36±0.16d
 

Diabetic+corilagin

(20 mg/kg body weight/day) 104.04±0.76bc 83.50±0.61c 48.95±0.66b 38.38±0.6c 16.70±0.12bc

 

 

 

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 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.

  1. 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.

  1. 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.

REFERENCES

 

 

  1. Aebi, H., 1984. Catalase in vitro. Methods Enzymol. 105, 121–6.
  1. Agardh, C.D., Bjorgell, P., Nilsson, E., 1999. The effect of tolbutamide on lipoproteins, lipoprotein lipase and hormone sensitive lipase. Diabetes Res Clin Pract. 46, 99–108.
  1. Ahad, A., Ganai, A.A., Mujeeb, M., Siddiqui, W.A., 2014. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats. Toxicol. Appl. Pharmacol. 279, 1–7. https://doi.org/10.1016/j.taap.2014.05.007
  1. Aissaoui, A., Zizi, S., Israili, Z.H., Lyoussi, B., 2011. Hypoglycemic and hypolipidemic effects of Coriandrum sativum L. in Meriones shawi rats. J. Ethnopharmacol. 137, 652– 661. https://doi.org/10.1016/j.jep.2011.06.019
  1. Beck-Nielsen, H., 2002. Insulin resistance: Organ manifestations and cellular mechanisms. Ugeskr. Laeger.164, 2130–2135.
  1. Bruce, A., Freeman, D., James, C., 1982. Biology of disease free radicals and tissue injury. Lab Invest. 47,412-426.
  1. Chaiyasut, C., Kusirisin, W., Lailerd, N., Lerttrakarnnon, P., Suttajit, M., Srichairatanakool, S., 2011. Effects of phenolic compounds of fermented thai indigenous plants on oxidative stress in streptozotocin-induced diabetic rats. Evidence-based Complement. Altern. Med. 2011. https://doi.org/10.1155/2011/749307
  1. Chakravarthy, B. K., Gupta, S., Gode, K. D., 1982. Functional β-cells regeneration in the islets of pancreas in alloxan induced diabetic rats by (-) epicatechin. Life Sci. 31, 2693– 269.
  1. Chance, B., Greenstein, D.S., Roughton, R.J.W., 1952. The mechanism of catalase action – steady state analysis. Arch Biochem Biophys. 37,301-339.
  1. Chauhan, A., Intelli., 2015. Syzygiumcumini(Jamun): Potential Benefits in Hyperglycemia. SOJ Pharm Pharm Sc. 2(3),1-3.
  1. Cheng, J.T., Lin, T.C., Hsu, F.L., 1995. Antihypertensive effect of corilagin in the rat. Can. J. Physiol. Pharmacol. 73, 1425–9. https://doi.org/10.1139/y95-198
  1. De-Sousa, E., Zanatta, L., Seifriz, I., Creczyski-Pasa, T. B., Pizzolatti, M. O., Szpoganicz, B., Silva, F. R., 2004. Hypoglycemic effect and antioxidant potential of kaempferol-3, 7-O- (alpha) – dirhamnoside from Bauhiniaforfictaleaves. J.Nat.Prod. 67, 829–832.
  1. El-Alfy, A. T., Ahmed, A. A., Fatani, A. J., 2005. Protective effect of red grape seeds proanthocyanidins against induction of diabetes by alloxan in rats. PharmacolRes. 52, 264–270.
  1. Friedewald, W.T., Levy, R.I., Fredrickson, D.S., 1972. Estimation of the concentration of LDL-C in plasma without the use of the preparative ultracentrifuge. Clin. Chem. 18,449– 502.
  1. Gambari, R., Borgatti, M., Lampronti, I., Fabbri, E., Brognara, E., Bianchi, N., Piccagli, L., Yuen, M.C.W., Kan, C.W., Hau, D.K.P., Fong, W.F., Wong, W.Y., Wong, R.S.M., Chui, C.H., 2012. Corilagin is a potent inhibitor of NF-kappaB activity and downregulates TNF- alpha induced expression of IL-8 gene in cystic fibrosis IB3-1 cells. Int. Immunopharmacol. 13, 308–315. https://doi.org/10.1016/j.intimp.2012.04.010
  1. Gaona-Gaona, L., Molina-Jijón, E., Tapia, E., Zazueta, C., Hernández-Pando, R., Calderón- Oliver, M., Zarco-Márquez, G., Pinzón, E., Pedraza-Chaverri, J., 2011. Protective effect of sulforaphane pretreatment against cisplatin-induced liver and mitochondrial oxidant damage in rats. Toxicology 286, 20–27. https://doi.org/10.1016/j.tox.2011.04.014
  1. Ghatak, S.B., Panchal, S.J., 2012. Anti-hyperlipidemic activity of oryzanol, isolated from crude rice bran oil, on Triton WR-1339-induced acute hyperlipidemia in rats. Revista brasileira de farmacognosia. 22,642–648.
  1. Grover, I.S.,  Bala,  S.,  1992.  Antimutagenic  activity  of Terminalia chebula(myroblan) in Salmonellatyphimurium. Indian J Exp Biol. 30(4), 339–341.
  1. Guo, Q., Du, G., Qi, H., Zhang, Y., Yue, T., Wang, J., Li, R., 2017. A Nematicidal tannin from Punica granatum L. rind and its physiological effect on pine wood nematode (Bursaphelenchus xylophilus). Pestic. Biochem. Physiol. 135, 64–68. https://doi.org/10.1016/j.pestbp.2016.06.003
  1. Guo, Y.J., Zhao, L., Li, X.F., Mei, Y.W., Zhang, S.L., Tao, J.Y., Zhou, Y., Dong, J.H., 2010. Effect of Corilagin on anti-inflammation in HSV-1 encephalitis and HSV-1 infected microglias. Eur. J. Pharmacol. 635, 79–86. https://doi.org/10.1016/j.ejphar.2010.02.049
  1. Han, J., Zhang, Z., Yang, S., Wang, J., Yang, X., Tan, D., 2014. Betanin attenuates paraquat- induced liver toxicity through a mitochondrial pathway. Food Chem Toxicol. 70,100–106.
  1. Hau, D.K.P., Gambari, R., Wong, R.S.M., Yuen, M.C.W., Cheng, G.Y.M., Tong, C.S.W., Zhu, G.Y., Leung, A.K.M., Lai, P.B.S., Lau, F.Y., Chan, A.K.W., Wong, W.Y., Kok, S.H.L., Cheng, C.H., Kan, C.W., Chan, A.S.C., Chui, C.H., Tang, J.C.O., Fong, D.W.F., 2009. Phyllanthus urinaria extract attenuates acetaminophen induced hepatotoxicity: Involvement of cytochrome P450 CYP2E1. Phytomedicine 16, 751–760.  https://doi.org/10.1016/j.phymed.2009.01.008
  1. Hissin, P.J., Hilf, R., 1976. A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal. Biochem. 74, 214–26.
  1. Honma, A., Koyama, T., Yazawa, K., 2010. Antihyperglycemic effects of Japanese maple Acer amoenum leaf extract and its constituent corilagin. J. Wood Sci. 56, 507–512.  https://doi.org/10.1007/s10086-010-1130-5

25. Hsu,  F.-L.,  Liu,  I.-M.,  Kuo,  D.-H.,  Chen,  W.-C.,  Su,  H.-C.,  Cheng,  J.-T.,  2003.

Antihyperglycemic Effect of Puerarin in Streptozotocin-Induced Diabetic Rats. J. Nat. Prod. 66, 788–792. https://doi.org/10.1021/np0203887

  1. International Diabetes Federation, 2014. Idf Diabetes Atlas 2014 Update. Diabetes Atlas, six Ed. https://doi.org/10.1016/j.diabres.2009.10.007
  1. Jia, L., Jin, H., Zhou, J., Chen, L., Lu, Y., Ming, Y., Yu, Y., 2013. A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-β signaling pathways. BMC Complement. Altern. Med. 13. https://doi.org/10.1186/1472- 6882-13-33
  1. Kavitha, K., Gopala Reddy, A., Kondal Reddy, K., Satish Kumar, C.S.V., Boobalan, G., Jayakanth, K., 2016. Hypoglycemic, hypolipidemic and antioxidant effects of pioglitazone, insulin and synbiotic in diabetic rats. Vet. World 9, 118–122. https://doi.org/10.14202/vetworld.2016.118-122
  1. Keenoy, B.M.Y., Campenhout, V.A., Aerts, P., Vertommen, J., Abrams, P., Gaal, L.F.V., Gils, C.V., Leeuw, I.H.D., 2005. Time course of oxidative stress status in the postprandial and postabsorptive states in type 1 diabetes mellitus: relationship to glucose and lipid changes. J Am College Nutr. 24(6), 474-485.
  1. Khan, K. H., 2009. Rols of Emblica officinalise in medicine – A review. Bot. Res. Int. 2, 218–228.
  1. King, G.L., Loeken, M.R., 2004. Hyperglycemia-induced oxidative stress in diabetic complications. Histochem. Cell Biol. https://doi.org/10.1007/s00418-004-06789
  1. Kinoshita,  S.,  Inoue,  Y.,  Nakama,  S.,  Ichiba,  T.,  Aniya,  Y.,  2007.  Antioxidant  and hepatoprotective actions of medicinal herb, Terminalia catappa L. from Okinawa Island

and its tannin corilagin. Phytomedicine 14, 755–762.

https://doi.org/10.1016/j.phymed.2006.12.012

  1. Kostyuk, V.A., Potapovich, A.I., 1989. Superoxide–driven oxidation of quercetin and a simple sensitive assay for determination of superoxide dismutase. Biochem. Int. 19, 1117– 24.
  1. Lee, J.S., 2006. Effects of soy protein and genistein on blood glucose, antioxidant enzyme activities, and lipid profile in streptozotocin-induced diabetic rats. Life Sci. 79, 1578–1584. https://doi.org/10.1016/j.lfs.2006.06.030
  1. Li, R., Zang, A., Zhang, L., Zhang, H., Zhao, L., Qi, Z., Wang, H., 2014. Chrysin ameliorates diabetes-associated cognitive deficits in Wistar rats. Neurol. Sci. 35, 1527– 1532.    https://doi.org/10.1007/s10072-014-1784-7
  1. Li, W., Zhang, M., Gu, J., Meng, Z.J., Zhao, L.C., Zheng, Y.N., Chen, L., Yang, G.L., 2012. Hypoglycemic effect of protopanaxadiol-type ginsenosides and compound K on Type 2 Diabetes mice induced by High-Fat Diet combining with Streptozotocin via suppression       of       hepatic       gluconeogenesis.       Fitoterapia       83,       192–198.

https://doi.org/10.1016/j.fitote.2011.10.011

  1. Matcovis, B., Varga, S.I., Szaluo Witsas, H., 1982. The effect of diabetes on the activities of the peroxide metabolic enzymes. Horm Metab Res. 14, 77- 79.
  1. McCord, J.M., Keele, B.B., Fridovich, I., 1976. An enzyme based theory of obligate anaerobiosis, the physiological functions of superoxide dismutase. Proc Natl Acad Sci USA. 68, 1024-1027.
  1. Muresan, X.M., Cervellati, F., Sticozzi, C., Belmonte, G., Chui, C.H., Lampronti, I., Borgatti, M., Gambari, R., Valacchi, G., 2015. The loss of cellular junctions in epithelial lung cells induced by cigarette smoke is attenuated by corilagin. Oxid. Med. Cell. Longev. 2015. https://doi.org/10.1155/2015/631758
  1. Okabe, S., Suganuma, M., Imayoshi, Y., Taniguchi, S., Yoshida, T., Fujiki, H., 2001. New TNF-alpha releasing inhibitors, geraniin and corilagin, in leaves of Acer nikoense, Megusurino-ki. Biol. Pharm. Bull. 24, 1145–8. https://doi.org/10.1248/bpb.24.1145
  1. Ozmutlu, S., Dede, S., Ceylan, E., 2012. The effect of lycopene treatment on ACE activity in rats with experimental diabetes. J Renin Angiotensin Aldosterone Syst. 13,328–333.
  1. Prisilla, D.H., Balamurugan, R., Shah, H.R., 2012. Antidiabetic activity of methanol extract of Acorus calamus in STZ induced diabetic rats. Asian Pacific J. Trop. Biomed. Asian Pacific   J.   Trop.   Biomed.   J.   homepage   941–946.   https://doi.org/10.1016/S2221-

1691(12)60341-4

  1. Raju, J., Gupta, D., Rao, A.R., Yadava, P.K., Baquer, N.Z., 2001. Trigonella foenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes. Mol. Cell. Biochem. 224, 45–51. https://doi.org/10.1023/A:1011974630828
  1. Ramesh, B., Pugalendi, K. V., 2005. Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats. Yale J. Biol. Med. 78, 187–194.
  2. Ramesh, B., Pugalendi, K. V, 2006. Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic              rats.              J.              Med.              Food              9,           562–566.

https://doi.org/10.1089/jmf.2006.9.562

  1. Ravi, K., Rajasekaran, S., Subramanian, S., 2005. Antihyperlipidemia effect of Eugeniajambolanaseed kernel on streptozotocin-induced diabetes in rats. Food Chem Toxicol. 43,1433-1439.
  1. Roselino, M.N., Pauly-Silveira, N.D., Cavallini, D.C.U., Celiberto, L.S., Pinto, R.A., Vendramini, R.C., Rossi, E.A., 2012. A potential synbiotic product improves the lipid profile of diabetic rats. Lipids Health Dis. 11. https://doi.org/10.1186/1476-511X-11-114
  1. Schmidt, O. T., Lademann, R., 1951. Corilagin, ein weiterer kristallisierter Gerbstoff aus Dividivi. X. Mitteilung über  natürliche  Gerbstoffe. Justus  Liebigs  Annalen  der Chemie. 571 (3), 232. doi: 10.1002/jlac.19515710305.
  1. Shisheva, A., Shechter, Y., 1992. Quercetin Selectively Inhibits Insulin Receptor Function in Vitro and the Bioresponses of Insulin and Insulinomimetic Agents in Rat Adipocytes. Biochemistry 31, 8059–8063. doi: 10.1021/bi00149a041
  1. Souto, S.B., Souto, E.B., Braga, D.C., Medina, J.L., 2011. Prevention and current onset delay approaches of type 2 diabetes mellitus (T2DM). Eur. J. Clin. Pharmacol.  https://doi.org/10.1007/s00228-011-1038-z
  1. Subash Babu, P., Prabuseenivasan, S., Ignacimuthu, S., 2007. Cinnamaldehyde-A potential antidiabetic              agent.              Phytomedicine              14,              15–22.

https://doi.org/10.1016/j.phymed.2006.11.005

  1. Suthagar, E., Soudamani, S., Yuvaraj, S., Ismail Khan, A., Aruldhas, M.M., Balasubramanian, K., 2009. Effects of streptozotocin (STZ)-induced diabetes and insulin replacement     on     rat     ventral     prostate.     Biomed.     Pharmacother.     63,     43–50.

https://doi.org/10.1016/j.biopha.2008.01.002

  1. Tahrani, A. A., Bailey, C.J., Del Prato, S., Barnett, A.H., 2011. Management of type 2 diabetes:    new    and    future    developments    in    treatment.    Lancet    378,    182–97.

https://doi.org/10.1016/S0140-6736 (11)60207-9

  1. Taskinen, M.R., Beltz, W.F., Harper. I., 1986. Effect of noninsulin dependent diabetes mellitus on VLDL, triglycerides and apolipoprotein B metabolism: Studies before and after sulfonylurea therapy. Diabetes. 35, 1268–1277.
  1. Wiernsperger, N.F., 2003. Oxidative stress as a therapeutic target in diabetes: Revisiting the controversy. Diabetes Metab. https://doi.org/10.1016/S1262-3636(07)70072-1
  1. Zheng, Z.Z., Chen, L.H., Liu, S.S., Deng, Y., Zheng, G.H., Gu, Y., Ming, Y.L., 2016. Bioguided Fraction and Isolation of the Antitumor Components from Phyllanthus niruri L. Biomed Res. Int. 2016. https://doi.org/10.1155/2016/972927

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

 

 

 

Control

 

 

187.4±1.54

 

 

214.2±1.37b

Diabetic Control 197.6±1.78 141±1.87a
Diabetic+Glibenclamide (0.1mg/kg body weight/day) 177.4±2.11 217.6±1.08b
Diabetic+corilagin (10 mg/kg body weight/day) 186±1.00 210.8±3.15b
Diabetic+ corilagin (20 mg/kg body weight/day) 187.8±1.95 212.4±2.58b

 

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.

 

 

 

Groups

 

 

Totalcholesterol(mg/dL)

 

 

Triglycerides(mg/dL)

 

 

HDLcholesterol

(mg/dL)

 

 

LDLcholesterol(mg/dL)

 

 

VLDLcholesterol(mg/dL)

 

 

Control

 

 

100.53±0.67a

 

 

79.58±0.76a

 

 

51.48±0.94d

 

 

33.13±1.26a

 

 

15.91±0.15a

Diabetic Control 162.34±0.61e 165.87±1.51e 33.87±0.76a 95.3±1.00e 33.17±0.30e
 

Diabetic+Glibenclamide (0.1mg/kg body weight/day)

 

103.06±1.47b

 

81.10±0.85b

 

50.12±0.94cd

 

36.72±2.03b

 

16.22±0.17ab

Diabetic+corilagin
(10 mg/kg body weight/day) 108.53±1.74d 86.81±0.82d 47.09±0.41b 44.08±1.73d 17.36±0.16d
Diabetic+corilagin
(20 mg/kg body weight/day) 104.04±0.76bc 83.50±0.61c 48.95±0.66b 38.38±0.6c 16.70±0.12bc

 

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.

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