Elsevier

Journal of Ethnopharmacology

Volume 113, Issue 3, 25 September 2007, Pages 479-486
Journal of Ethnopharmacology

Influence of tetrahydrocurcumin on erythrocyte membrane bound enzymes and antioxidant status in experimental type 2 diabetic rats

https://doi.org/10.1016/j.jep.2007.07.004Get rights and content

Abstract

Curcuma longa (Zingiberaceae) has been used traditionally as antidiabetic and has been proven scientifically to possess high antioxidant activity and anticancer properties. The active components of Curcuma longa such as curcumin and tetrahydrocurcumin (THC), a major colourless metabolite of curcumin also possesses antidiabetic, antiinflammatory and antioxidant activity. In the present study the effect of THC and curcumin on erythrocyte membrane bound enzymes and antioxidants activity in streptozotocin (STZ) and nicotinamide induced type 2 diabetic model was investigated. Oral administration of THC at 80 mg/kg body weight to diabetic rats for 45 days. The effect of THC and curcumin on glucose, insulin, haemoglobin, glycosylated haemoglobin, thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), glutathione-S-transferase (GST), reduced glutathione (GSH) and membrane bound enzymes were studied. The effect of THC was compared with curcumin. The levels of blood glucose, glycosylated haemoglobin, erythrocyte TBARS, were increased significantly whereas the level of plasma insulin and haemoglobin, erythrocyte antioxidants (SOD, CAT, GPx, GST and GSH), membrane bound total ATPase, Na+/K+-ATPase, Ca2+-ATPase, Mg2+-ATPase were decreased significantly in diabetic rats. Administration of THC and curcumin to diabetic rats showed decreased level of blood glucose, glycosylated haemoglobin and erythrocyte TBARS. In addition the levels of plasma insulin, haemoglobin, erythrocyte antioxidants and the activities of membrane bound enzymes also were increased in THC and curcumin treated diabetic rats. These biochemical observations were supplemented by histopathological examination of pancreas section. The present study indicates that the THC possesses a significant beneficial effect on erythrocyte membrane bound enzymes and antioxidants defense in addition to its antidiabetic effect.

Introduction

Diabetes is a major health problem affecting major populations worldwide. Epidemiological studies and clinical trials strongly support the notion that hyperglycaemia is the principal cause of complications. Erythrocyte membrane hyper polarization was found in diabetic cells as a result of constant oxidative stress that can be responsible for long term complications in diabetes (Augustyniak et al., 1996). Changes in membrane lipid composition and enzymatic properties of membrane bound enzymes are shown to occur in diabetes. The enhancement of non-enzymatic glycosylation diabetic extends beyond haemoglobin to the proteins of the of the erythrocyte membranes. Erythrocytes are highly sensitive to peroxidative damage probably due to the high content of unsaturated fatty acid in their membrane. Therefore, the fair degree of ATPases activities in erythrocyte membrane could be serving as simple, safe and useful marker of intracellular damage (Ohta et al., 1989).

Curcumin (diferuloylmethane) is the substance that gives the spice to turmeric, which is extensively used in Indian cuisine as a component of curry powder, its yellow colour. Curcumin is extracted from the roots of the Curcuma longa plant (turmeric). It is believed that curcumin is a potent antioxidant and antiinflammatory agent. Practitioners of traditional Indian medicine believe that curcumin powder is beneficial against many diseases including biliary disorders, diabetes, hepatic disorders, rheumatism, sinusitis, cancer and Alzheimer disease (Aggarwal et al., 2003). In experimental studies, curcumin has been shown to reduce the hyperlipidemia (Babu and Srinivasan, 1997), delay the development of cataract (Suryanarayana et al., 2005), ameliorate the renal lesions (Babu and Srinivasan, 1998) and reduce the cross-linking of collagen (Sajithlal et al., 1998) in a streptozotocin (STZ)-induced diabetic animal model. Curcumin has also been shown to lower blood glucose levels in type 2 diabetic KK-Ay mice (Nishiyama et al., 2005) and STZ treated rats (Mahesh et al., 2005).

Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin. Structurally, THC and curcumin have identical β-diketone structures and phenolic groups, but differ in that THC lacks the double bonds (Okada et al., 2001). Recently, attention has focused on THC, because this compound appears to exert greater antioxidant activity in both in vitro and in vivo systems (Okada et al., 2001). Sugiyama et al. (1996) demonstrated that THC exhibited similar physiological and pharmacological properties as the active form of curcumin in vivo. Naito et al. (2002) showed clear involvement of THC in biochemical and molecular actions at the cellular level in ameliorating oxidative stress in cholesterol-fed rabbits. Furthermore, Okada et al. (2001) have claimed that THC has more potent antioxidant activity than curcumin. In our previous study, we have demonstrated the antidiabetic effect of THC in STZ and nicotinamide induced diabetic rats (Pari and Murugan, 2005, Murugan and Pari, 2006).

To our knowledge, so far no other biochemical investigations have been carried out on the effect of THC in erythrocyte antioxidants and the activities of membrane bound enzymes of experimental diabetic rats. The present investigation was carried out to study the effect of THC on erythrocyte antioxidants and the activities of membrane bound enzymes in rats with STZ and nicotinamide induced diabetes.

Section snippets

Animals

Adult male albino Wistar rats (8 weeks), weighing 180–200 g bred in the Central Animal House, Rajah Muthiah Medical College, Annamalai University, were used. All animal experiments were approved by the ethical committee (Vide. No. 284, 2005), Annamalai University and were in accordance with the guidelines of the National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India. The animals were housed in polycarbonate cages in a room with a 12 h day:12 h night cycle,

Results

Fig. 1, Fig. 2 show the level of blood glucose, total haemoglobin, glycosylated haemoglobin and plasma insulin of different experimental groups. There was a significant elevation in blood glucose level, whereas plasma insulin levels decreased significantly in diabetic rats, compared with normal rats. Administration of THC and curcumin tended to bring blood glucose and plasma insulin towards normal. The diabetic control rats showed a significant decrease in the level of total haemoglobin and

Discussion

Type 2 diabetes is the most prevalent and serious metabolic disease affecting people all over the world. Pancreatic β-cell dysfunction and insulin resistance are the hallmark of type 2 diabetes. Administration of THC increased the activity of antioxidants and may help to control free radical, as THC and curcumin offered protection to cells against oxidative stress by scavenging free radicals (Okada et al., 2001) generated during diabetes (Anusuya and Menon, 2003). The increased levels of free

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