Endocrine pharmacology Protective effect of ferulic acid and resveratrol against alloxan-induced diabetes in mice Manikandan Ramar a,n , Beulaja Manikandan b , Thiagarajan Raman c , Asokan Priyadarsini b , Subramanian Palanisamy a , Meiyalagan Velayudam b , Arumugam Munusamy b , Narayanan Marimuthu Prabhu a , Baskaralingam Vaseeharan a a Department of Animal Health and Management, Science block, Alagappa University, Karaikudi 630 003, India b Department of Zoology, University of Madras, Guindy campus, Chennai 600 025, India c Department of Biotechnology, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401, India article info Article history: Received 12 January 2012 Received in revised form 25 April 2012 Accepted 15 May 2012 Available online 31 May 2012 Keywords: Diabetes Alloxan Ferulic acid Resveratrol Nuclear factor-kB abstract The present study was to investigate the effect of ferulic acid and resveratrol on alloxan-induced diabetic mice, through analysis of basic biochemical parameters, enzymic as well as non-enzymic activities, lipid peroxidation and immunohistochemical studies. Alloxan was administered as a single dose (75 mg/kg body weight) to induce diabetes in mice. A dose of ferulic acid (10 mg/kg body weight) and resveratrol (20 mg/kg body weight) were administrated orally, to the alloxan-induced diabetic mice. The levels of basic biochemical markers and lipid peroxidation were significantly (P o0.05) increased in alloxan-induced diabetic mice. The levels of antioxidants were significantly (P o0.05) decreased in liver, kidney and serum. Immunohistochemical studies in alloxan induced mice demon- strated a marked increase in the immunoreactivity of nuclear transcription factor (NF-kB). Treating the diabetic mice with doses of ferulic acid and resveratrol restored the changes in the above parameters analyzed. The present study, showed that ferulic acid and resveratrol exerted antioxidant as well as anti-diabetic effects, consequently alleviate liver, kidney and pancreas damage caused by alloxan- induced diabetes, probably through inhibition of the proinflammatory factor, NF  kB. & 2012 Published by Elsevier B.V. 1. Introduction Diabetes mellitus is a chronic disease caused by inherited and/ or acquired deficiency in production of insulin by pancreas, or by ineffectiveness of the insulin produced. Such a deficiency results in increased concentration of blood glucose, which in turn damages many bodily systems, in particular blood vessels and nerves. As the number of people with diabetes mellitus increases worldwide, the disease has taken an ever increasing share of national and international health care budgets, and indeed the World Health Organization (WHO) has reported that 300 million people would suffer diabetes mellitus by the year 2025 (Pradeepa and Mohan, 2002). Diabetes mellitus is one of the serious problems in developing as well as developed countries (Kumar et al., 2007). It is characterized by absolute or relative deficiencies in insulin secretion and/or insulin action associated with chronic hyperglycaemia and disturbances of carbohydrate, lipid and protein metabolism (Duckworth, 2001). Diabetes mellitus is a pathologic condition, regulating severe meta- bolic imbalances and non-physiologic changes in many tissues, where oxidative stress plays an important role in aetiology (Yue et al., 2003; Orsolic and Basic, 2008). Diabetes is associated with the generation of reactive oxygen species, which cause oxidative damage, particularly to kidney, liver, eyes, small and large blood vessels, immunological and gastrointestinal system (Obrosova et al., 2003; Yue et al., 2003; Orsolic and Basic, 2008). The pathophysiology of diabetes involves a very complex cascade of several interrelated mechanism. Elevated blood glu- cose induced auto-oxidative glycosylation, formation of glycation product, protein kinase-C activation and activation of nuclear transcription factor (Kumar et al., 2007). NF-kB is a transcription factor that can be activated by a variety of stress and increased polyol pathway activity. These pathways are responsible for generation of reactive oxygen species and peroxynitrite, which ultimately contribute to the oxidative stress (Brownlee, 2001; Kaul and Ramarao, 2001; Sima, 2003; Ahmed, 2005; Wada and Yagihashi, 2005). Oxidative stress exerts its devastating effects either by directly damaging cellular proteins, lipids and DNA, or indirectly by affecting normal cellular signaling as well as gene regulation (Blasiak et al., 2003). Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/ejphar European Journal of Pharmacology 0014-2999/$ - see front matter & 2012 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.ejphar.2012.05.019 n Corresponding author. Tel.: þ91 9941064724. E-mail address: manikandanramar@yahoo.co.in (M. Ramar). European Journal of Pharmacology 690 (2012) 226–235