Cytotoxic Effects of Gallic Acid and its Derivatives Against HIV-I-infected Microglia.
10.4167/jbv.2016.46.4.239
- Author:
Jin Ju JEONG
1
;
Yong Sup LEE
;
Dong Hyun KIM
Author Information
1. Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Korea. dhkim@khu.ac.kr
- Publication Type:Original Article
- Keywords:
HIV-1;
Macrophage;
Gallic acid;
Methyl 4-O-methyl gallate
- MeSH:
Cycloheximide;
Flavonoids;
Gallic Acid*;
Ginsenosides;
Glycogen Synthase;
HIV-1;
Humans;
Macrophages;
Microglia*;
Oxidoreductases;
Phosphorylation;
Phosphotransferases;
Pyruvic Acid
- From:Journal of Bacteriology and Virology
2016;46(4):239-247
- CountryRepublic of Korea
- Language:English
-
Abstract:
In the previous study, we found that flavonoids and ginsenosides exhibited high eliminate rates of human immunodeficiency virus type 1 (HIV-1) D3-transfected macrophages. Based on these findings, here we synthesized the derivatives of gallic acid, including methyl gallate, methyl 4-O-methyl gallate, methyl 3,4-O-dimethyl gallate, and methyl 3,4,5-O-trimethyl gallate and measured their cellular toxic effects against HIV-1-infected macrophages. Of these, treatment with methyl 4-O-methyl gallate in the presence of lipopolysaccharide (LPS) and cycloheximide (CHX) most effectively eliminated HIV-1-transfected cytoprotective human microglial CHME5 cells and HIV-1-D3-infected human primary macrophages. Furthermore, these strongly inhibited LPS/CHX-induced phosphorylation of phosphoinositide 3-kinase (PI3K), pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK1), Akt, and glycogen synthase kinase-3β (GSK-3β) in the Tat-transfected cells and HIV-1-D3-infected human primary macrophages. These findings suggest that methyl 4-O-methyl gallate may be a promising candidate for eliminating HIV-1 infected macrophages by blocking PI3K/Akt signaling pathway.
