Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues

• Published in: Biochimica et biophysica acta Vol. 1760; no. 1; pp. 70 - 77
• Main Authors: Wei, Qing-Yi, Chen, Wei-Feng, Zhou, Bo, Yang, Li, Liu, Zhong-Li
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 2006
• Subjects: Animals; Antioxidants - chemical synthesis; Antioxidants - pharmacology; Antioxidation; Curcumin; Curcumin - analogs & derivatives; Curcumin - pharmacology; Female; Kinetics; Lipid peroxidation; Lipid Peroxidation - drug effects; Mitochondria, Liver - metabolism; Oxidation-Reduction - drug effects; Phenolic antioxidant; Protein carbonyl; Proteins - metabolism; Rat liver mitochondria; Rats; Rats, Wistar; Structure-Activity Relationship; Thiobarbituric Acid Reactive Substances; PBS; DNPH; SDS; DPPH; AAPH; Lipid peroxidation; Structure/activity relationship; TBARS; Rat liver mitochondria; EDTA; BHT; TBA; TCA; Curcumin; Phenolic antioxidant; Protein carbonyl; Antioxidation
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2005.09.008

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a yellow ingredient isolated from turmeric ( curcumin longa). It has been shown to exhibit a variety of biological activities including antioxidative activity. In order to find more active antioxidants with 1 as the lead compound we synthesized curcumin analogues, i.e., 1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione ( 2), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione ( 3), 1,7-bis-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione ( 4), 1-(3,4-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione ( 5), 1,7-bis(3,4-dimethoxyphenyl)-1,6-heptadiene-3,5-dione ( 6), and 1,7-diphenyl-1,6-heptadiene-3,5-dione ( 7), and evaluated their antioxidative activity. The in vitro oxidative damage to both lipids and proteins in rat liver mitochondria was used as a model to study the free radical-induced oxidative damage of biological lipids as well as proteins and the protective effects of these curcumin analogues. It was found that these compounds, except 6 and 7, could effectively inhibit the free radical induced lipid peroxidation and protein oxidative damage of rat liver mitochondria by H-atom abstraction from the phenolic groups. Compound 2 which bear ortho-diphenoxyl functionality exhibited remarkably higher antioxidative activity for lipids and proteins than curcumin and other analogues, and the 4-hydroxy-3-methoxyphenyl group also play an important role in the antioxidative activity.