Thesis (M.Sc.)--Chulalongkorn University, 2007

Oxidative modification of low-density lipoprotein (LDL) plays a major role in the pathogenesis of atherosclerosis. Hemin, a degradation product of hemoglobin, is one of oxidative mediator elevated in pathological cases like severe hemoglobinopathies, sickle cell anemia and thalassemia. The rhizome of Curcuma longa L. contain bioactive substances referred to as curcuminoids, including curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), and these molecules have antioxidant and anti-inflammatory activities. The objective of this study is to compare the protective effect of curcuminoids, curcumin, DMC, BDMC and tetrahydrocurcumin (THC) on hemin induced LDL oxidation (he-oxLDL). The pre-incubation of LDL with various concentrations of the tested compounds were performed; and then oxidized by 2.5 [Micromolar]hemin/150 [Microgram] LDL protein. α-Tocopherol was used as a positive control. He-oxLDL at 24 hour-oxidation was shown by the depletion of [alpha]-tocopherol, the increase of the thiobarbituric acid reactive substances (TBARs) level and the alteration of lipid composition in LDL. The levels of cholesteryl arachidonate (CA) and cholesteryl linoleate (CL) were decreased by 28.88% and 24.24% (p<0.05) respectively, including the CL/CO ratio was also decreased. All tested compounds possess an antioxidant activity which protects hemin-induced lipid peroxidation by inhibition of TBARs formation, the depletion of [alpha]-tocopherol, the decrease of lipid (CA and CL) and decreased of CL/CO ratio in a concentration dependent manner. The 50% inhibition concentration (IC₅₀) of the damage of CA were 4.5, 9.3, 10.4, 25.5, 47.3, and 65.9 [Micromolar]and those of CL were 5.5, 6.0, 10.8, 16.5, 30.0 and 60.4 [Micromolar]for THC, curcumin, curcuminoids, DMC, BDMC and [alpha]-tocopherol, respectively. In addition, when compare the effect of tested compounds 10 [Micromolar]found that these tested compounds were able to inhibit rate of TBARs formation and decreasing rate of [alpha]-tocopherol. THC has a comparable effect with curcumin and curcuminoids to inhibit these rate and more than DMC, BDMC and [alpha]- tocopherol respectively. We conclude that a significant protective effect on he-oxLDL is in the order of THC ≥ curcumin ≥ curcuminoids > DMC > BDMC > [alpha]- tocopherol (p<0.05).