Pidaran Murugan

EFFECT OF TETRAHYDROCURCUMIN ON BLOOD GLUCOSE, PLASMA INSULIN AND HEPATIC KEY ENZYMES IN STREPTOZOTOCIN INDUCED DIABETIC RATS

The enzymes of glucose and lipid metabolism are markedly altered in experimental diabetes. In the present study, we investigated the effect of tetrahydrocurcumin (THC), one of the active metabolites in curcumin, on the key hepatic metabolic enzymes involved in carbohydrate metabolism in streptozotocin-induced diabetic rats. Different doses of THC (20, 40, and 80 mg\kg body weight) were orally administered to diabetic rats for 45 days. The activities of hexokinase, glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, fructose-1,6-bisphosphatase, and sorbitol dehydrogenase in liver, and glycogen content in liver and muscle were assayed. In untreated diabetic control rats, the activities of the gluconeogenic enzymes were significantly increased, whereas hexokinase and G6PD activity and glycogen levels were significantly decreased. Both THC and curcumin were able to restore the altered enzyme activities to near normal levels. Tetrahydrocurcumin was more effective than curcumin. Our results indicate that the administration of THC to diabetic animals normalizes blood glucose and causes a marked improvement of altered carbohydrate metabolic enzymes.

Antihyperlipidemic Effect of Curcumin and Tetrahydrocurcumin in Experimental Type 2 Diabetic Rats

Hyperlipidemia is an associated complication of diabetes mellitus. In the present study, we investigated the effect of tetrahydrocurcumin (THC), one of the active metabolites of curcumin on lipid profile in streptozotocin (STZ)-nicotinamide-induced diabetic rats. THC 80mg/kg body weight was orally administered to diabetic rats for 45 days, resulting in a significant reduction in blood glucose and a significant increase in plasma insulin in diabetic rats, which proved that THC possess an antidiabetic effect. THC also caused a significant reduction serum and liver cholesterol, triglycerides, free fatty acids, phospholipids, HMG CoA reductase activity, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol levels. The decreased serum high-density lipoprotein (HDL) cholesterol in diabetic rats was also reversed toward normalization after the treatment. These biochemical observations were supplemented by histopathological examination of liver section. The effect was compared with curcumin (80 mg/kg body weight). The results showed that THC had antihyperlipidemic action in control and experimental diabetic rats. The antidiabetic and antihyperlipidemic effects of THC are more potent than those of curcumin at the same dose.

Effect of tetrahydrocurcumin on insulin receptor status in type 2 diabetic rats: studies on insulin binding to erythrocytes

Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin, and exhibits many of the same physiological and pharmacological activities as curcumin and, in some systems, may exert greater antioxidant activity than curcumin. Using circulating erythrocytes as the cellular mode, the insulin-binding effect of THC and curcumin was investigated. Streptozotocin (STZ)-nicotinamide-induced male Wistar rats were used as the experimental models. THC (80 mg/kg body weight) was administered orally for 45 days. The effect of THC on blood glucose, plasma insulin and insulin binding to its receptor on the cell membrane of erythrocytes were studied. Mean specific binding of insulin was significantly lowered in diabetic rats with a decrease in plasma insulin. This was due to a significant decrease in mean insulin receptors. Erythrocytes from diabetic rats showed a decreased ability for insulin-receptor binding when compared with THC-treated diabetic rats. Scatchard analysis demonstrated that the decrease in insulin binding was accounted for by a decrease in insulin receptor sites per cell, with erythrocytes of diabetic rats having less insulin receptor sites per cell than THC-treated rats. High affinity (Kd1), low affinity (Kd2) and kinetic analyses revealed an increase in the average receptor affinity of erythrocytes from THC-treated rats compared with those of diabetic rats. These results suggest that acute alteration of the insulin receptor on the membranes of erythrocytes occurred in diabetic rats. Treatment with THC significantly improved specific insulin binding to the receptors, with receptor numbers and affinity binding reaching near-normal levels. Our study suggests the mechanism by which THC increases the number of total cellular insulin binding sites resulting in a significant increase in plasma insulin. The effect of THC is more prominent than that of curcumin.

Influence of tetrahydrocurcumin on tail tendon collagen contents and its properties in rats with streptozotocin–nicotinamide‐induced type 2 diabetes

Changes in the structural and functional properties of collagen caused by advanced glycation might be of importance for the etiology of late‐stage complications in diabetics. Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti‐inflammatory agent. Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin, exhibiting many of the same physiological and pharmacological activities of curcumin and in some systems may exert greater antioxidant activity than curcumin. In diabetic rats, hydroxyproline and collagen content as well as its degree of cross‐linking were increased, as shown by increased extent of glycation, collagen‐linked fluorescence, neutral salt collagen, and decreased acid and pepsin solubility. Administration of THC for 45 days to diabetic rats significantly reduced the accumulation and cross‐linking of collagen. The effects of THC were comparable with those of curcumin. In conclusion, administration of THC had a positive influence on the content of collagen and its properties in streptozotocin‐ and nicotinamide‐induced diabetic rats. THC was found to be more effective than curcumin.

Effect of tetrahydrocurcumin on erythromycin estolate-induced lipid peroxidation in rats.

Erythromycin estolate (EME), a potent macrolide antibiotic, generates free radicals, but their role in the development of liver toxicity is not yet well understood. The present study was carried out to investigate the effect of the antioxidant drug tetrahydrocurcumin (a metabolite of curcumin, the main component of turmeric) against EME-induced lipid peroxidation in rats. The oral administration of combined THC (80 mg/kg body weight) and EME (800 mg/kg body weight) for 15 days significantly decreased lipid peroxidation and enhanced cellular antioxidant defenses when compared with the group treated with EME alone. Supplemental histopathological examination of liver sections revealed that THC had a better antioxidant effect than Silymarin (200 mg/kg body weight), a reference drug. The results of this study indicate that THC affords significant protection against EME-induced lipid peroxidation.