Gallotannin isolated from Euphorbia species, 1,2,6-tri-O-galloyl-beta-D-allose, decreases nitric oxide production through inhibition of nuclear factor-kappa>B and downstream inducible nitric oxide synthase expression in macrophages.
Gallotannins are plant secondary metabolites and are widely included to polyphenolic compounds. Gallotannins are water-soluble polyphenols with wide-ranging biological activities. Nitric oxide (NO) is well known as a mediator of inflammation. Macrophages express inducible nitric oxide synthase (iNOS) and produce NO after lipopoly saccharide (LPS) stimulation. In the present study, we examined the inhibitory effects of seven gallotannins isolated from Euphorbia species (Euphorbiaceae) on the LPS-induced NO production and underlying mechanisms of action. Among the seven gallotannins, 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (gallotannin 15) and 1,2,6-tri-O-galloyl-beta-D-allose (gallotannin 23) significantly reduced LPS-induced NO production in macrophages. Gallotannin 15 and 23 (0.1-10 microg/ml) dose-dependently decreased gene expression and production of iNOS. In addition, gallotannin 15 and 23 (0.1-10 microg/ml) dose-dependently inhibited LPS-induced activation of nuclear factor (NF)-kappaB as indicated by inhibition of degradation of I-kappaBalpha, nuclear translocation of NF-kappaB, and NF-kappaB-dependent gene reporter assay. Our results suggest that gallotannins possess an inhibitory effect on the LPS-induced inflammatory reaction.
Kim
Mi-Sun
MS
CMRI, IHBR, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Park
Seung-Bin
SB
Suk
Kyoungho
K
Kim
In Kyeom
IK
Kim
Sang-Yong
SY
Kim
Jeong-Ah
JA
Lee
Seung Ho
SH
Kim
Sang-Hyun
SH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D028481:Euphorbia / Q000737:chemistry*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C542188:1,2,6-tri-O-galloyl-beta-D-allose; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047348:Hydrolyzable Tannins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C433788:lipopolysaccharide, E. coli O26-B6; D009569:Nitric Oxide; D005707:Gallic Acid; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D005947:Glucose