PYCNOGENOL ® IS EFFECTIVE IN MILD TYPE DIABETES IN RATS 1169 Copyright © 2009 John Wiley & Sons, Ltd. Phytother. Res. 23, 1169–1174 (2009) DOI: 10.1002/ptr Copyright © 2009 John Wiley & Sons, Ltd. PHYTOTHERAPY RESEARCH Phytother. Res. 23, 1169–1174 (2009) Published online 22 January 2009 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/ptr.2776 Pycnogenol ® Efficiency on Glycaemia, Motor Nerve Conduction Velocity and Markers of Oxidative Stress in Mild Type Diabetes in Rats S. Jankyova 1 , P. Kucera 2 , Z. Goldenberg 2 , D. Yaghi 1 , J. Navarova 3 , Z. Kyselova 3 , S. Stolc 3 , J. Klimas 1 , E. Racanska 1 and S. Matyas 1 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic 2 1st Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic 3 Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic The aim of this study was to describe the effects of Pycnogenol ® at various doses on preprandial and postprandial glucose levels, the levels of thiobarbituric acid reactive substances (TBARs) and N-acetyl- β β β-D-glucosaminidase (NAGA) and on motor nerve conduction velocity (MNCV) in streptozotocin (STZ)-induced diabetic rats. Pycnogenol ® treatment (10, 20, 50 mg/kg body weight (b.w.)/day) lasted for 8 weeks after induction of diabetes. Pycnogenol ® significantly decreased elevated levels of preprandial glycaemia in treated animals at all doses. At doses of 10 mg/kg b.w./day and 20 mg/kg b.w./day it significantly decreased elevated levels of postprandial glycaemia compared with diabetic non-treated animals. Pycnogenol ® failed to induce a significant decrease of postprandial glycaemia at a dose of 50 mg/kg b.w./day. Pycnogenol ® improved significantly the impaired MNCV at doses of 10 and 20 mg/kg b.w./day compared with non-treated animals. The levels of TBARs were elevated in diabetic rats. The levels of NAGA increased gradually despite the treatment. Pycnogenol ® failed to affect the increased levels of TBARs and NAGA. Pycnogenol ® lowered the elevated levels of glycaemia and reduced the decline in motor nerve conduction velocity in STZ-induced diabetic rats. The effect of Pycnogenol ® on postprandial glycaemic levels and MNCV was not dose-dependent. Copyright © 2009 John Wiley & Sons, Ltd. Keywords: diabetes; glycaemia; Pycnogenol ® ; MNCV; TBARs; NAGA. Received 29 September 2008 Revised 3 December 2008 Accepted 3 December 2008 * Correspondence to: S. Jankyova, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovak Republic. E-mail: jankyova@fpharm.uniba.sk Contract/grant sponsor: Comenius University, Bratislava and Ministry of Education of the Slovak Republic; Contract/grant number: UK 283/2007; UK 315/2007; FaF UK/35/2008; FaF UK/39/2008; VEGA SR 2/5129/25. INTRODUCTION Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycaemia resulting from defects in insulin secretion or insulin action, or both, and is accompanied by many diabetic complications, arising mainly from high levels of blood glucose (Expert Com- mittee on the Diagnosis and Classification of Diabetes Mellitus, 2003). Hyperglycaemia leads to the genera- tion of free radicals, which consequently create oxidative stress in tissues (Ceriello, 2003). Oxidative stress occurs as the result of excess and/or deficient breakdown of high reactive oxygen or nitrogen species and leads to damage of cells and organs, changes in enzyme activities and to increased lipid peroxidation (Maritim et al., 2003b). It is the result of an imbalance between reac- tive oxygen species (i.e. hydroxyl radical, superoxide anion and H 2 O 2 ) and antioxidant compounds, such as superoxide dismutase, catalase, glutathione, vitamin C or vitamin E (van Dam, 2002). There are different pathways which involve oxidative stress and can lead to cell and tissue damage: e.g. glucose autooxidation (Dobretsov et al., 2007), interaction between glycated endproducts and their receptors (Hayden and Tyagi, 2004), overproduction of reactive oxygen species and polyol pathway (Cumbie and Hermayer, 2007). All these factors together sustain damage to the neuronal unit either directly or by endothelial dysfunction, which progresses as the result of oxidative stress (van Dam, 2002). There are also other changes accompanying diabetes, which are involved in the development of diabetic neuropathy, such as a decrease in nerve congestion, local hypoxia, injuries of the mitochondria and nerve cell apoptosis (Veves and King, 2001). Lipid peroxida- tion, which may increase cell membrane rigidity and impair cell function, occurs due to high glycaemic levels (Pari and Latha, 2004). One of the products of lipid peroxidation is malondialdehyde, which can be assessed as the concentration of thiobarbituric acid reactive sub- stances (TBARs) (Quine and Raghu, 2005). Sotnikova et al. (2006) reported increased lysosomal enzyme activity as one of the first signs of tissue injury due to inadequate oxygen supply, which can be determined as the concentration of N-acetyl-β-D-glucosaminidase (NAGA). Oxidative stress in neurons is responsible for the development of axonopathy, impaired regenera- tion of neurons and for the development of peripheral diabetic neuropathy (Dobretsov et al., 2007). Diabetic neuropathies are common complications of diabetes