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Synthesized pyridine compound derivatives decreased TNF alpha and adhesion molecules and ameliorated HSV-induced inflammation in a mouse model

Authors
 Bunsoon Choi  ;  Joohyon Kim  ;  Eun-So Lee  ;  Dongsik Bang  ;  Seonghyang Sohn 
Citation
 EUROPEAN JOURNAL OF PHARMACOLOGY, Vol.657(1-3) : 167-172, 2011 
Journal Title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN
 0014-2999 
Issue Date
2011
MeSH
Administration, Oral ; Animals ; Behcet Syndrome/drug therapy ; Behcet Syndrome/genetics ; Behcet Syndrome/metabolism* ; Behcet Syndrome/virology* ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism* ; Cell Line ; Disease Models, Animal ; Down-Regulation/drug effects ; Humans ; Male ; Mice ; Molecular Weight ; Naphthyridines/administration & dosage ; Naphthyridines/chemical synthesis ; Naphthyridines/chemistry ; Naphthyridines/pharmacology ; Pyridines/administration & dosage ; Pyridines/chemical synthesis ; Pyridines/chemistry* ; Pyridines/pharmacology* ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Simplexvirus/physiology* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/biosynthesis ; Tumor Necrosis Factor-alpha/metabolism*
Keywords
Pyridine compound derivative ; Behcet's disease ; Herpes simplex virus ; TNF alpha ; Oral administration ; Anti-inflammation ; Mouse model
Abstract
Synthesized pyridine compound derivatives (SK94, SK126) from a natural lead source were administered to mice to test for possible anti-TNF alpha and anti-inflammatory activities. Lipopolysaccharide (LPS)-induced TNF alpha production was analyzed in the endothelial cells, Raw 264.7 cells, and serum of normal mice after treatment with SK compounds. These compounds were also orally administered to a herpes simplex virus (HSV)-induced Behcet's disease mouse model to investigate their anti-inflammatory therapeutic effect. TNF alpha production was inhibited in a dose-dependent manner in the SK94 treated cells. E-selectin, VCAM-1, and ICAM-1 mRNA levels were also down-regulated. Treatment with 30mg/kg SK94 inhibited 55% of the TNF alpha production in LPS challenged Balb/c mice (n=8). SK94 and SK126 were administered to the Behcet's disease-like mice for five consecutive days and SK94 improved in five out of six mice (83%), while it only improved in one out of nine mice (11%) in the pH 1.2 saline (artificial gastric juice) group (P<0.005), four out of ten mice (40%) in the thalidomide group (P<0.05), and six out of seven (86%) in the SK126 group (P<0.005). Soluble ICAM-1 was inhibited by 23.8% in the sera of SK94 treated mice and by 34.6% in SK126 treated mice when compared to artificial gastric juice. Based on these findings, SK compounds could be candidates for clinical trials.
Full Text
http://www.sciencedirect.com/science/article/pii/S0014299911001208
DOI
10.1016/j.ejphar.2011.01.062
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Bang, Dong Sik(방동식)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/93005
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