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Natural Product Research: Formerly Natural Product Letters Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/gnpl20
Protective effects of grape seed extract fractions with different degrees of polymerisation on blood glucose, lipids and hepatic oxidative stress in diabetic rats a
a
b
a
Zhaoxia Wu , Siyao Shen , Jiaqian Jiang , Dehong Tan , Donghua a
a
a
Jiang , Bing Bai , Xiyun Sun & Shichen Fu
a
a
Click for updates
College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning Province 110866, P.R. China b
College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, Liaoning Province 110866, P.R. China Published online: 07 Oct 2014.
To cite this article: Zhaoxia Wu, Siyao Shen, Jiaqian Jiang, Dehong Tan, Donghua Jiang, Bing Bai, Xiyun Sun & Shichen Fu (2014): Protective effects of grape seed extract fractions with different degrees of polymerisation on blood glucose, lipids and hepatic oxidative stress in diabetic rats, Natural Product Research: Formerly Natural Product Letters, DOI: 10.1080/14786419.2014.965165 To link to this article: http://dx.doi.org/10.1080/14786419.2014.965165
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
Downloaded by [McMaster University] at 19:00 16 February 2015
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
Natural Product Research, 2014 http://dx.doi.org/10.1080/14786419.2014.965165
SHORT COMMUNICATION Protective effects of grape seed extract fractions with different degrees of polymerisation on blood glucose, lipids and hepatic oxidative stress in diabetic rats
Downloaded by [McMaster University] at 19:00 16 February 2015
Zhaoxia Wua*, Siyao Shena, Jiaqian Jiangb, Dehong Tana, Donghua Jianga, Bing Baia, Xiyun Suna and Shichen Fua a College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning Province 110866, P.R. China; bCollege of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, Liaoning Province 110866, P.R. China
(Received 17 May 2014; final version received 10 September 2014) The purpose of this study was to evaluate the effect of grape seed procyanidin (GSPE) fractions with different degrees of polymerisation (DPs) on blood glucose, lipids and hepatic oxidative stress in diabetic rats. Diabetic rats received a daily oral supplement of GSPE with different DPs for 6 weeks. During this period, blood glucose, body weight and food intake were assessed weekly. At the end of the experiment, serum lipid and hepatic oxidative stress were assessed compared with those of rats that did not receive GSPE. GSPE significantly decreased blood glucose, serum lipids and hepatic oxidative stress. Moreover, these effects were significantly better in the groups administered the oligomeric rather than the polymeric forms. These results demonstrate that GSPE has a positive effect on diabetes in rats, and the oligomeric form of GSPE may be more protective than other forms. Keywords: procyanidins; antioxidation; diabetes; nitric oxide
1. Introduction Diabetes is a chronic metabolic disorder that represents a major global health problem and is characterised by an abnormal elevation of blood glucose, termed hyperglycaemia, which has been associated with oxidative stress (Bonnefont-Rousselot et al. 2004). It is estimated that the number of people with diabetes will increase from 171 million in 2000 to 366 million in 2030 (Wild et al. 2004). Grape seed procyanidins (GSPEs) are a mixture of monomers (þ )-catechin, (2 )epicatechin, (2 )-epicatechin-O-gallate and (2 )-epigallocatechin (Labarbe et al. 1999) derived from the flavan-3-ol class of flavonoids, which are widely distributed in red grape seeds. Some studies have reported that the monomers themselves confer blood glucose-lowering effects (Matsumoto et al. 1993; Kao et al. 2000; Shimizu et al. 2000; Waltner-Law et al. 2002; Kim et al. 2003), while considerable research has focused on the effect of GSPE mixtures on blood glucose levels and pathological oxidative stress in diabetic states (Pinent et al. 2004; El-Alfy et al. 2005; Cheng et al. 2007; Chis et al. 2009; Kar et al. 2009; Chedea et al. 2010). However, little information is available regarding the specific glucose-lowering effect of degrees of polymerisation (DPs). The identification of an optimal GSPE DPs would allow for the target DP compounds to be isolated or synthesised for diabetes treatment.
*Corresponding author. Email: [email protected] q 2014 Taylor & Francis
2
Z. Wu et al.
Therefore, we conducted an experiment to evaluate the effects of GSPE fractions with different DPs on diabetes in rats following 6 weeks of supplementation with the GSPE fractions. Diabetes was induced using streptozocin (STZ) in rats that had been fed a high-energy diet. The effects on blood glucose levels, serum lipid levels and hepatic oxidative stress were evaluated and compared with those in rats that did not receive treatment, received standard antidiabetic treatment or did not have diabetes.
Downloaded by [McMaster University] at 19:00 16 February 2015
2. Results and discussion 2.1. Effect of GSPE on blood glucose Figure S1 illustrates the changes in fasting blood glucose over the 6-week period. Treatment with metformin hydrochloride, which is an oral antidiabetic drug in the biguanide category and the drug of choice for first-line treatment of type 2 diabetes, and the GSPE fractions resulted in significantly lower blood glucose levels than in the untreated diabetic model (DM) rats starting at week 4. However, there were no significant differences between the GSPE supplementation with different DPs, and the use of GSPE had a similar effect on the blood glucose level as metformin hydrochloride.
2.2. Effect of GSPE on body weight All of the groups commenced the experiment with similar average body weights. Following the various treatments, body weight increased in all groups except the DM group that did not receive treatment (Figure S2). From week 3, the difference in body weight between the GSPE-treated groups (oligomeric GSPE [DO], polymeric GSPE with DP of 6.5 [PG1] and polymeric GSPE with DP of 11.8 [PG2]) and DM group increased, resulting in a significant difference after 5 weeks. Furthermore, the DO and PG1 groups gained more weight than the PG2 group.
2.3. Effect of GSPE on 24-h food intake The non-diabetic normal (ND) group maintained their intake during the study period, while the diabetic groups, including those receiving treatment, significantly increased their food intake (Figure S3). The 24-h food intakes in the proanthocyanidin-administered groups were significantly lower than that of the DM group after week 4. There were no significant differences between the different DPs. Table 1. Effect of GSPEs with different DPs on serum lipids in rats. Group
TG (mmol/L)
TC (mmol/L)
HDL (mmol/L)
LDL (mmol/L)
ND DM DO PG1 PG2 MH
0.41 ^ 0.11 1.58 ^ 0.18d 0.96 ^ 0.03b 1.40 ^ 0.12c 1.44 ^ 0.13c 0.98 ^ 0.07b
1.25 ^ 0.10 1.77 ^ 0.17c 1.56 ^ 0.09b 1.60 ^ 0.10b 1.73 ^ 0.09c 1.44 ^ 0.05b
0.87 ^ 0.07 0.60 ^ 0.02c 0.71 ^ 0.04b 0.63 ^ 0.04c 0.61 ^ 0.03c 0.72 ^ 0.04b
0.37 ^ 0.07a 0.54 ^ 0.01b 0.50 ^ 0.02b 0.52 ^ 0.05b 0.54 ^ 0.03b 0.49 ^ 0.03b
a
a
a
Notes: TG, triglycerides; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ND, nondiabetic normal group; DM, diabetic model group; DO, oligomeric proanthocyanidin group (degree of polymerisation [DP] ¼ 3.2); DP1, polymeric proanthocyanidin group 1 (DP ¼ 6.5); PG2, polymeric proanthocyanidin group 2 (DP ¼ 11.8); MH, metformin hydrochloride group. All the values are in mean ^ SD and the differences between the groups were analysed using one-way ANOVA. The letters indicate statistically significant differences between treatments: P , 0.05 (Tukey tests).
2.24 ^ 0.11 5.45 ^ 0.25d 4.47 ^ 0.23b 5.00 ^ 0.28cd 5.25 ^ 0.10d 4.65 ^ 0.28bc
27.52 ^ 1.12 21.22 ^ 1.33c 23.39 ^ 0.88b 22.73 ^ 1.02bc 22.49 ^ 0.93bc 23.35 ^ 1.26b
193.23 ^ 33.31 143.47 ^ 16.06b 174.19 ^ 10.28ab 160.75 ^ 11.70b 169.55 ^ 14.89ab 175.76 ^ 17.84a
ND DM DO PG1 PG2 MH
0.10 ^ 0.12 2.76 ^ 0.22a 1.94 ^ 0.12c 2.51 ^ 0.16ab 2.69 ^ 0.25a 2.17 ^ 0.32bc d
NO (mmol/L) 0.87 ^ 0.30 0.47 ^ 0.04b 0.62 ^ 0.02b 0.51 ^ 0.03b 0.50 ^ 0.02b 0.60 ^ 0.04b a
GSH (g GSH/L)
230.19 ^ 9.67 180.47 ^ 10.99c 197.23 ^ 14.44b 193.67 ^ 5.43bc 190.11 ^ 2.42bc 202.53 ^ 3.45b a
GSH-ST (U/mg prot)
294.78 ^ 20.19a 217.47 ^ 13.68c 244.46 ^ 13.27b 237.08 ^ 10.97b 231.54 ^ 8.47bc 245.57 ^ 20.50b
GSH-Px (U/mg prot)
Notes: SOD, superoxide dismutase; CAT, hydrogen peroxidase; MDA, malondialdehyde; NO, nitric oxide; GSH, glutathione; GSH-ST, GSH S-transferase; GSH-Px, GSH peroxidase; ND, non-diabetic normal group; DM, diabetic model group; DO, oligomeric proanthocyanidin group, group (degree of polymerisation [DP] ¼ 3.2); PG1, polymeric proanthocyanidin group 1 (DP ¼ 6.5); PG2, polymeric proanthocyanidin group 2 (DP ¼ 11.8); MH, metformin hydrochloride group. All the values are in mean ^ SD and the differences between the groups were analysed using one-way ANOVA. The letters indicate statistically significant differences between treatments: P , 0.05 (Tukey tests).
a
MDA (nmol/mg prot)
a
CAT (U/mg prot)
a
SOD (U/mg prot)
Group
Table 2. Effect of GSPEs with different DPs on hepatic oxidative stress levels in rats.
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2.4. Effect of GSPE on serum lipids Chronic hyperglycaemia results in increased serum cholesterol and triglyceride (TG) levels. As shown in Table 1, the serum concentrations of TG, total cholesterol (TC) and low-density lipoprotein (LDL) significantly decreased, and high-density lipoprotein (HDL) concentration significantly increased in the DO group compared with the DM group, although all of the diabetic groups had significantly poorer values than the ND rats. DO and metformin resulted in similar effects. Moreover, the two polymeric proanthocyanidin groups (PG1 and PG2) did not have improved lipid levels compared with the DM group. It appears that the lower DP of the DO group mediated the effect of GSPE on blood lipids.
2.5. Effect of GSPE on hepatic oxidative stress The effects of GSPE administration on hepatic oxidative stress are shown in Table 2. DO and metformin resulted in similar effects. There were no significant differences between the GSPE groups, except in malondialdehyde (MDA) and nitric oxide (NO) levels in the DO group, with improved elimination of MDA and NO in this group.
3. Conclusions The type 2 diabetes model used in this study was successfully achieved by feeding adult Sprague-Dawley rats a high-fat diet (40% of calories as fat) for 2 weeks followed by an injection of STZ. In these type 2 diabetes model rats, GSPE extracted from grape seed demonstrated a positive effect on blood glucose levels in addition to lowering TG, TC and LDL levels while increasing the HDL level, thereby modulating the effect of hyperlipidaemia. The changes in MDA, NO, SOD, CAT, GSH-Px and GSH-ST provide further evidence that GSPE may be effective in the treatment of diabetes. Of the GSPE DPs used in this study, the oligomers (DP ¼ 3.2) demonstrated the best results. Many of the available antidiabetic pharmaceutical drugs have side effects such as hepatic and/or renal dysfunction and gastrointestinal reactions. In comparison, oligomeric GSPE, which is naturally derived from plants and demonstrates the properties of high efficiency, low toxicity and high biological utilisation, may be promising as a phytochemical option to reduce the oxidative stress induced by hyperglycaemia and aid in the prevention and treatment of diabetes.
Supplementary material Experimental materials relating to this article are available online, alongside Figures S1 –S3.
References Bonnefont-Rousselot D, Beaudeux JL, The´rond P, Peynet J, Legrand A, and Delattre J. (2004). Diabetes mellitus, oxidative stress and advanced glycation endproducts. Annales Pharmaceutiques Franc aises. 62:147–157. Chedea VS, Braicu C, Socaciu C. 2010. Antioxidant/prooxidant activity of a polyphenolic grape seed extract. Food Chem. 121:132–139. Cheng M, Gao HQ, Xu L, Li BY, Zhang H, Li XH. 2007. Cardioprotective effects of grape seed proanthocyanidins extracts in streptozocin induced diabetic rats. J Cardiovasc Pharmacol. 50:503–509. Chis IC, Ungureanu MI, Marton A, Simedrea R, Muresan A, Postescu ID, Decea N. 2009. Antioxidant effects of a grape seed extract in a rat model of diabetes mellitus. Diabetes Vasc Dis Res. 6:200–204. El-Alfy AT, Ahmed AA, Fatani AJ. 2005. Protective effect of red grape seeds proanthocyanidins against induction of diabetes by alloxan in rats. Pharma Res. 52:264– 270. Kao YH, Hiipakka RA, Liao S. 2000. Modulation of endocrine systems and food intake by green tea epigallocatechin gallate. Endocrinology. 141:980–987.
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Kar P, Laight D, Rooprai HK, Shaw KM, Cummings M. 2009. Effects of grape seed extract in type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabetic Med. 26:526–531. Kim MJ, Ryu GR, Chung JS, Sim SS, Min DS, Rhie DJ, Yoon SH, Hahn SJ, Kim MS, Jo YH. 2003. Protective effects of epicatechin against the toxic effects of streptozotocin on rat pancreatic islets: in vivo and in vitro. Pancreas. 26:292–299. Labarbe B, Cheyneir V, Brossaud F, Souquet JM, Moutounet M. 1999. Quantitative fractionation of grape proanthocyanidins according to their degree of polymerization. J Agric Food Chem. 47:2719–2723. Matsumoto N, Ishigaki F, Ishigaki A, Iwashina H, Hara Y. 1993. Reduction of blood glucose levels by tea catechin. Biosci Biotechnol Biochem. 57:525–527. Pinent M, Blay M, Blade´ MC, Salvado´ MJ, Arola L, Arde´vol A. 2004. Grape seed-derived procyanidins have an antihyperglycemic effect in streptozotocin-induced diabetic rats and insulinomimetic activity in insulin-sensitive cell lines. Endocrinology. 145:4985–4990. Shimizu M, Kobayashi Y, Suzuki M, Satsu H, Miyamoto Y. 2000. Regulation of intestinal glucose transport by tea catechins. Biofactors. 13:61–65. Waltner-Law ME, Wang XL, Law BK, Hall RK, Nawano M, Granner DK. 2002. Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J Biol Chem. 277:34933–34940. Wild S, Roglic G, Green A, Sicree R, King H. 2004. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 27:1047– 1053.
Natural Product Research: Formerly Natural Product Letters Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/gnpl20
Protective effects of grape seed extract fractions with different degrees of polymerisation on blood glucose, lipids and hepatic oxidative stress in diabetic rats a
a
b
a
Zhaoxia Wu , Siyao Shen , Jiaqian Jiang , Dehong Tan , Donghua a
a
a
Jiang , Bing Bai , Xiyun Sun & Shichen Fu
a
a
Click for updates
College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning Province 110866, P.R. China b
College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, Liaoning Province 110866, P.R. China Published online: 07 Oct 2014.
To cite this article: Zhaoxia Wu, Siyao Shen, Jiaqian Jiang, Dehong Tan, Donghua Jiang, Bing Bai, Xiyun Sun & Shichen Fu (2014): Protective effects of grape seed extract fractions with different degrees of polymerisation on blood glucose, lipids and hepatic oxidative stress in diabetic rats, Natural Product Research: Formerly Natural Product Letters, DOI: 10.1080/14786419.2014.965165 To link to this article: http://dx.doi.org/10.1080/14786419.2014.965165
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
Downloaded by [McMaster University] at 19:00 16 February 2015
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
Natural Product Research, 2014 http://dx.doi.org/10.1080/14786419.2014.965165
SHORT COMMUNICATION Protective effects of grape seed extract fractions with different degrees of polymerisation on blood glucose, lipids and hepatic oxidative stress in diabetic rats
Downloaded by [McMaster University] at 19:00 16 February 2015
Zhaoxia Wua*, Siyao Shena, Jiaqian Jiangb, Dehong Tana, Donghua Jianga, Bing Baia, Xiyun Suna and Shichen Fua a College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning Province 110866, P.R. China; bCollege of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, Liaoning Province 110866, P.R. China
(Received 17 May 2014; final version received 10 September 2014) The purpose of this study was to evaluate the effect of grape seed procyanidin (GSPE) fractions with different degrees of polymerisation (DPs) on blood glucose, lipids and hepatic oxidative stress in diabetic rats. Diabetic rats received a daily oral supplement of GSPE with different DPs for 6 weeks. During this period, blood glucose, body weight and food intake were assessed weekly. At the end of the experiment, serum lipid and hepatic oxidative stress were assessed compared with those of rats that did not receive GSPE. GSPE significantly decreased blood glucose, serum lipids and hepatic oxidative stress. Moreover, these effects were significantly better in the groups administered the oligomeric rather than the polymeric forms. These results demonstrate that GSPE has a positive effect on diabetes in rats, and the oligomeric form of GSPE may be more protective than other forms. Keywords: procyanidins; antioxidation; diabetes; nitric oxide
1. Introduction Diabetes is a chronic metabolic disorder that represents a major global health problem and is characterised by an abnormal elevation of blood glucose, termed hyperglycaemia, which has been associated with oxidative stress (Bonnefont-Rousselot et al. 2004). It is estimated that the number of people with diabetes will increase from 171 million in 2000 to 366 million in 2030 (Wild et al. 2004). Grape seed procyanidins (GSPEs) are a mixture of monomers (þ )-catechin, (2 )epicatechin, (2 )-epicatechin-O-gallate and (2 )-epigallocatechin (Labarbe et al. 1999) derived from the flavan-3-ol class of flavonoids, which are widely distributed in red grape seeds. Some studies have reported that the monomers themselves confer blood glucose-lowering effects (Matsumoto et al. 1993; Kao et al. 2000; Shimizu et al. 2000; Waltner-Law et al. 2002; Kim et al. 2003), while considerable research has focused on the effect of GSPE mixtures on blood glucose levels and pathological oxidative stress in diabetic states (Pinent et al. 2004; El-Alfy et al. 2005; Cheng et al. 2007; Chis et al. 2009; Kar et al. 2009; Chedea et al. 2010). However, little information is available regarding the specific glucose-lowering effect of degrees of polymerisation (DPs). The identification of an optimal GSPE DPs would allow for the target DP compounds to be isolated or synthesised for diabetes treatment.
*Corresponding author. Email: [email protected] q 2014 Taylor & Francis
2
Z. Wu et al.
Therefore, we conducted an experiment to evaluate the effects of GSPE fractions with different DPs on diabetes in rats following 6 weeks of supplementation with the GSPE fractions. Diabetes was induced using streptozocin (STZ) in rats that had been fed a high-energy diet. The effects on blood glucose levels, serum lipid levels and hepatic oxidative stress were evaluated and compared with those in rats that did not receive treatment, received standard antidiabetic treatment or did not have diabetes.
Downloaded by [McMaster University] at 19:00 16 February 2015
2. Results and discussion 2.1. Effect of GSPE on blood glucose Figure S1 illustrates the changes in fasting blood glucose over the 6-week period. Treatment with metformin hydrochloride, which is an oral antidiabetic drug in the biguanide category and the drug of choice for first-line treatment of type 2 diabetes, and the GSPE fractions resulted in significantly lower blood glucose levels than in the untreated diabetic model (DM) rats starting at week 4. However, there were no significant differences between the GSPE supplementation with different DPs, and the use of GSPE had a similar effect on the blood glucose level as metformin hydrochloride.
2.2. Effect of GSPE on body weight All of the groups commenced the experiment with similar average body weights. Following the various treatments, body weight increased in all groups except the DM group that did not receive treatment (Figure S2). From week 3, the difference in body weight between the GSPE-treated groups (oligomeric GSPE [DO], polymeric GSPE with DP of 6.5 [PG1] and polymeric GSPE with DP of 11.8 [PG2]) and DM group increased, resulting in a significant difference after 5 weeks. Furthermore, the DO and PG1 groups gained more weight than the PG2 group.
2.3. Effect of GSPE on 24-h food intake The non-diabetic normal (ND) group maintained their intake during the study period, while the diabetic groups, including those receiving treatment, significantly increased their food intake (Figure S3). The 24-h food intakes in the proanthocyanidin-administered groups were significantly lower than that of the DM group after week 4. There were no significant differences between the different DPs. Table 1. Effect of GSPEs with different DPs on serum lipids in rats. Group
TG (mmol/L)
TC (mmol/L)
HDL (mmol/L)
LDL (mmol/L)
ND DM DO PG1 PG2 MH
0.41 ^ 0.11 1.58 ^ 0.18d 0.96 ^ 0.03b 1.40 ^ 0.12c 1.44 ^ 0.13c 0.98 ^ 0.07b
1.25 ^ 0.10 1.77 ^ 0.17c 1.56 ^ 0.09b 1.60 ^ 0.10b 1.73 ^ 0.09c 1.44 ^ 0.05b
0.87 ^ 0.07 0.60 ^ 0.02c 0.71 ^ 0.04b 0.63 ^ 0.04c 0.61 ^ 0.03c 0.72 ^ 0.04b
0.37 ^ 0.07a 0.54 ^ 0.01b 0.50 ^ 0.02b 0.52 ^ 0.05b 0.54 ^ 0.03b 0.49 ^ 0.03b
a
a
a
Notes: TG, triglycerides; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ND, nondiabetic normal group; DM, diabetic model group; DO, oligomeric proanthocyanidin group (degree of polymerisation [DP] ¼ 3.2); DP1, polymeric proanthocyanidin group 1 (DP ¼ 6.5); PG2, polymeric proanthocyanidin group 2 (DP ¼ 11.8); MH, metformin hydrochloride group. All the values are in mean ^ SD and the differences between the groups were analysed using one-way ANOVA. The letters indicate statistically significant differences between treatments: P , 0.05 (Tukey tests).
2.24 ^ 0.11 5.45 ^ 0.25d 4.47 ^ 0.23b 5.00 ^ 0.28cd 5.25 ^ 0.10d 4.65 ^ 0.28bc
27.52 ^ 1.12 21.22 ^ 1.33c 23.39 ^ 0.88b 22.73 ^ 1.02bc 22.49 ^ 0.93bc 23.35 ^ 1.26b
193.23 ^ 33.31 143.47 ^ 16.06b 174.19 ^ 10.28ab 160.75 ^ 11.70b 169.55 ^ 14.89ab 175.76 ^ 17.84a
ND DM DO PG1 PG2 MH
0.10 ^ 0.12 2.76 ^ 0.22a 1.94 ^ 0.12c 2.51 ^ 0.16ab 2.69 ^ 0.25a 2.17 ^ 0.32bc d
NO (mmol/L) 0.87 ^ 0.30 0.47 ^ 0.04b 0.62 ^ 0.02b 0.51 ^ 0.03b 0.50 ^ 0.02b 0.60 ^ 0.04b a
GSH (g GSH/L)
230.19 ^ 9.67 180.47 ^ 10.99c 197.23 ^ 14.44b 193.67 ^ 5.43bc 190.11 ^ 2.42bc 202.53 ^ 3.45b a
GSH-ST (U/mg prot)
294.78 ^ 20.19a 217.47 ^ 13.68c 244.46 ^ 13.27b 237.08 ^ 10.97b 231.54 ^ 8.47bc 245.57 ^ 20.50b
GSH-Px (U/mg prot)
Notes: SOD, superoxide dismutase; CAT, hydrogen peroxidase; MDA, malondialdehyde; NO, nitric oxide; GSH, glutathione; GSH-ST, GSH S-transferase; GSH-Px, GSH peroxidase; ND, non-diabetic normal group; DM, diabetic model group; DO, oligomeric proanthocyanidin group, group (degree of polymerisation [DP] ¼ 3.2); PG1, polymeric proanthocyanidin group 1 (DP ¼ 6.5); PG2, polymeric proanthocyanidin group 2 (DP ¼ 11.8); MH, metformin hydrochloride group. All the values are in mean ^ SD and the differences between the groups were analysed using one-way ANOVA. The letters indicate statistically significant differences between treatments: P , 0.05 (Tukey tests).
a
MDA (nmol/mg prot)
a
CAT (U/mg prot)
a
SOD (U/mg prot)
Group
Table 2. Effect of GSPEs with different DPs on hepatic oxidative stress levels in rats.
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2.4. Effect of GSPE on serum lipids Chronic hyperglycaemia results in increased serum cholesterol and triglyceride (TG) levels. As shown in Table 1, the serum concentrations of TG, total cholesterol (TC) and low-density lipoprotein (LDL) significantly decreased, and high-density lipoprotein (HDL) concentration significantly increased in the DO group compared with the DM group, although all of the diabetic groups had significantly poorer values than the ND rats. DO and metformin resulted in similar effects. Moreover, the two polymeric proanthocyanidin groups (PG1 and PG2) did not have improved lipid levels compared with the DM group. It appears that the lower DP of the DO group mediated the effect of GSPE on blood lipids.
2.5. Effect of GSPE on hepatic oxidative stress The effects of GSPE administration on hepatic oxidative stress are shown in Table 2. DO and metformin resulted in similar effects. There were no significant differences between the GSPE groups, except in malondialdehyde (MDA) and nitric oxide (NO) levels in the DO group, with improved elimination of MDA and NO in this group.
3. Conclusions The type 2 diabetes model used in this study was successfully achieved by feeding adult Sprague-Dawley rats a high-fat diet (40% of calories as fat) for 2 weeks followed by an injection of STZ. In these type 2 diabetes model rats, GSPE extracted from grape seed demonstrated a positive effect on blood glucose levels in addition to lowering TG, TC and LDL levels while increasing the HDL level, thereby modulating the effect of hyperlipidaemia. The changes in MDA, NO, SOD, CAT, GSH-Px and GSH-ST provide further evidence that GSPE may be effective in the treatment of diabetes. Of the GSPE DPs used in this study, the oligomers (DP ¼ 3.2) demonstrated the best results. Many of the available antidiabetic pharmaceutical drugs have side effects such as hepatic and/or renal dysfunction and gastrointestinal reactions. In comparison, oligomeric GSPE, which is naturally derived from plants and demonstrates the properties of high efficiency, low toxicity and high biological utilisation, may be promising as a phytochemical option to reduce the oxidative stress induced by hyperglycaemia and aid in the prevention and treatment of diabetes.
Supplementary material Experimental materials relating to this article are available online, alongside Figures S1 –S3.
References Bonnefont-Rousselot D, Beaudeux JL, The´rond P, Peynet J, Legrand A, and Delattre J. (2004). Diabetes mellitus, oxidative stress and advanced glycation endproducts. Annales Pharmaceutiques Franc aises. 62:147–157. Chedea VS, Braicu C, Socaciu C. 2010. Antioxidant/prooxidant activity of a polyphenolic grape seed extract. Food Chem. 121:132–139. Cheng M, Gao HQ, Xu L, Li BY, Zhang H, Li XH. 2007. Cardioprotective effects of grape seed proanthocyanidins extracts in streptozocin induced diabetic rats. J Cardiovasc Pharmacol. 50:503–509. Chis IC, Ungureanu MI, Marton A, Simedrea R, Muresan A, Postescu ID, Decea N. 2009. Antioxidant effects of a grape seed extract in a rat model of diabetes mellitus. Diabetes Vasc Dis Res. 6:200–204. El-Alfy AT, Ahmed AA, Fatani AJ. 2005. Protective effect of red grape seeds proanthocyanidins against induction of diabetes by alloxan in rats. Pharma Res. 52:264– 270. Kao YH, Hiipakka RA, Liao S. 2000. Modulation of endocrine systems and food intake by green tea epigallocatechin gallate. Endocrinology. 141:980–987.
Downloaded by [McMaster University] at 19:00 16 February 2015
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