OBJECTIVETo assess the efficacy of curcumin in delaying development of type 2 diabetes mellitus (T2DM) in the prediabetic population.RESEARCH DESIGN AND METHODSThis randomized, double-blinded, placebo- controlled trial included subjects (n = 240) with criteria of prediabetes. All subjects were randomly assigned to receive either curcumin or placebo capsules for 9 months. To assess the T2DM progression after curcumin treatments and to determine the number of subjects progressing to T2DM, changes in β-cell functions (homeostasis model assessment [HOMA]-β, C-peptide, and proinsulin/insulin), insulin resistance (HOMA-IR), anti-inflammatory cytokine (adiponectin), and other parameters were monitored at the baseline and at 3-, 6-, and 9-month visits during the course of intervention.RESULTSAfter 9 months of treatment, 16.4% of subjects in the placebo group were diagnosed with T2DM, whereas none were diagnosed with T2DM in the curcumin-treated group. In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (61.58 vs. 48.72; P < 0.01) and lower C-peptide (1.7 vs. 2.17; P < 0.05). The curcumin-treated group showed a lower level of HOMA-IR (3.22 vs. 4.04; P < 0.001) and higher adiponectin (22.46 vs. 18.45; P < 0.05) when compared with the placebo group.CONCLUSIONSA 9-month curcumin intervention in a prediabetic population significantly lowered the number of prediabetic individuals who eventually developed T2DM. In addition, the curcumin treatment appeared to improve overall function of β-cells, with very minor adverse effects. Therefore, this study demonstrated that the curcumin intervention in a prediabetic population may be beneficial.

Oxidative stress plays a major role in the pathogenesis of various diseases including neurodegenerative diseases, myocardial ischemia-reperfusion injury and cancer. Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5,-dione], the principal yellow pigment isolated from turmeric (Curcuma longa Linn), is known as a potent antioxidant comparable to a-tocopherol. Its antioxidant activities have been studied in several in vitro models. 1) Despite its poor bioavailability, 2-4) the therapeutic benefits of curcumin in animals have been demonstrated in several oxidative stress models such as Alzheimer's disease, 5) ethanol induced oxidative injury in brain, liver, heart and kidney, 6,7) and myocardial ischemic damage.8) It is possible that the metabolites of curcumin could mediate major antioxidant activities in vivo.In mouse, curcumin is first biotransformed to dihydrocurcumin (DHC) and tetrahydrocurcumin (THC) and these compounds are subsequently converted to monoglucuronide conjugates including curcumin-glucuronide, dihydrocurcuminglucuronide and tetrahydrocurcumin-glucuronide. 9) In human and rat hepatocytes, curcumin is metabolized into curcumin glucuronide, curcumin sulfate, THC, hexahydrocurcumin (HHC) and octahydrocurcumin (OHC). 10,11) Antioxidant activities of THC have already been studied both in vitro and in vivo. Venkatesan et al. 12) reported that THC had higher activity than curcumin in protecting the nitrite induced oxidation of haemoglobin and lysis of erythrocytes. THC has also been demonstrated to be more potent than curcumin in protection against ferric nitrilotriacetate (Fe-NTA) induced oxidative renal damage in mice. 13) THC produces this protective effect to cells against oxidative stress by scavenging of free radicals, 14) inhibition of lipid peroxidation and formation of hydroperoxides. 15) To the best of our knowledge, the antioxidant activities of HHC and OHC have not been reported.We are also interested in the antioxidant activities of natural demethoxyl derivatives of curcumin, demethoxycurcumin (Dmc) and bisdemethoxycurcumin (Bdmc), which are always found together with curcumin in tumeric extracts and in commercial preparation of curcumin. Antioxidant activities of Dmc and Bdmc have been reported in the model systems of hydroxyl radical induced DNA damage, 16) DPPH radical scavenging activity 17) and recently in lipid peroxidation. 18)However, to date, there has been no comparative study on the antioxidant activities of curcumin with its natural demethoxy derivatives and metabolite hydrogenated derivatives. In particular, the ability to provide protection against lipid and cell membrane damage of all of those derivatives has not yet been reported. The aim of this study is to compare the antioxidant activities of curcumin, its demethoxy derivatives (Dmc and Bdmc), and hydrogenated derivatives (THC, HHC and OHC) using three in vitro models: radical scavenging activity by DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, AAPH [2,2Ј-azobis(2-amidinopropane)dihydrochloride] induced linole...

Inhibition of nitric oxide synthesis with N ( ω )-nitro-L-arginine methyl ester (L-NAME) induces marked hypertension and oxidative stress. Curcumin (CUR) has been shown strong antioxidant property. Tetrahydrocurcumin (THU), a major metabolite of CUR, possesses several pharmacological effects similar to CUR; however, it is less studied than CUR. We investigated whether CUR and THU could prevent vascular dysfunction and inhibit development of hypertension in L-NAME-treated rats. Male Sprague-Dawley rats were administered with L-NAME (50 mg/kg/day) in drinking water for 3 weeks. CUR or THU (50 and 100 mg/kg/day) was fed to animals simultaneously with L-NAME. L-NAME administration induced increased arterial blood pressure and elevated peripheral vascular resistance accompanied with impaired vascular responses to angiotensin II and acetylcholine. CUR and THU significantly suppressed the blood pressure elevation, decreased vascular resistance, and restored vascular responsiveness. The improvement of vascular dysfunction was associated with reinstating the marked suppression of eNOS protein expression in the aortic tissue and plasma nitrate/nitrite. Moreover, CUR and THU reduced vascular superoxide production, decreased oxidative stress, and increased the previously depressed blood glutathione (GSH) and the redox ratios of GSH in L-NAME hypertensive rats. The antihypertensive and some antioxidant effects of THU are apparently more potent than those of CUR. This study suggests that CUR and THU prevented the development of vascular dysfunction induced by L-NAME and that the effects are associated with alleviation of oxidative stress.

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Tetrahydrocurcumin (THC), a major metabolite of curcumin, possesses strong antioxidant and cardioprotective properties. However, the activities of THC in hypertension and its associated complications remain unknown. The aim of this study was to investigate the effect of THC on hemodynamic status, aortic elasticity and oxidative stress in rats with N-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Hypertension was induced in male Sprague-Dawley rats by administration of L-NAME (50 mg kg(-1) body weight) in drinking water for 5 weeks. THC at a dose of 50 or 100 mg kg(-1) per day was administered daily during the fourth and fifth weeks when the hypertensive state had been established. The effects of THC on hemodynamics, aortic elasticity, endothelial nitric oxide synthase (eNOS) protein expression and oxidative stress markers were assessed. Marked increases in blood pressure, peripheral vascular resistance, aortic stiffness and oxidative stress were found in rats after L-NAME administration. THC significantly reversed these deleterious effects by reducing aortic wall thickness and stiffness. These effects were associated with increased aortic eNOS expression, elevated plasma nitrate/nitrite, decreased oxidative stress with reduced superoxide production and enhanced blood glutathione. Our results provide the first evidence that THC attenuates the detrimental effect of L-NAME by improving the hemodynamic status and aortic elasticity concomitant with reduction of oxidative stress. The present study suggests that THC might be used as a dietary supplement to protect against cardiovascular alterations under nitric oxide-deficient conditions.