Journal of Pharmaceutical and Biomedical Sciences

Apocynin Dimer Derivatives Combining a-Lipoic Acid Protected RAW 264.7 Macrophage Cells from Oxidative Injury Induced by Lipopolysaccharide

Lingchao Zhu, Jianghong Man, Zhijian Zhang, Gaofang Wang, Jie Jiang | Vol 08 | Issue 05 | Pp:74-78.

Abstract


Apocynin, a classical nicotinamide adenine dinucleotide phosphate-oxidase, has been widely studied in various oxidative stress related diseases. a-Lipoic acid (LA) is a natural strong antioxidant, which has been commonly used to ameliorate oxidative injury in cell and animal models. To enhance the anti-oxidative activity, three new apocynin dimer derivatives combining LA, JJA-D5, D6 and D7, was designed and synthesized on the basic structure of apocynin dimer analogue JJA-D0. It has been generally believed that apocynin and its derivatives exerted anti-oxidative action through inhibiting NADPH oxidase. Preliminary docking simulation of the three derivatives with 1K4U subsection of human neutrophil NADPH oxidase system was performed to predict the binding capacity using GOLD 5.0.1 software. The derivatives got higher binding score than apocynin, indicating stronger interaction between the derivative and NADPH oxidase, and more potential anti-oxidative action was expected. The anti-oxidative protection of JJA-D5, D6 and D7 was investigated in RAW 264.7 macrophage cells treated with lipopolysaccharide. The results demonstrated that apocynin and the three derivatives increased cell viability at 10 and 100 ?M when compared with model group, the protective effect of JJA-D5, D6 and D7 was generally higher than apocynin at 10 and 100 ?M, and some groups had significant difference (P < 0.05). It indicated that combining LA may obtained apocynin dimer derivatives of potential anti-oxidative protection.


Keywords


apocynindimer derivative, a-lipoic acid, anti-oxidative protection

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