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

Authors
Choi, B; Kim, J; Lee, ES; Bang, D; Sohn S
Citation
European journal of pharmacology, 657(1-3):167-172, 2011
Journal Title
European journal of pharmacology
ISSN
0014-29991879-0712
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.
MeSH terms
Administration, OralAnimalsBehcet Syndrome/drug therapy/genetics/*metabolism/*virologyCell Adhesion Molecules/genetics/*metabolismCell LineDisease Models, AnimalDown-Regulation/drug effectsHumansMaleMiceMolecular WeightNaphthyridines/administration & dosage/chemical synthesis/chemistry/pharmacologyPyridines/administration & dosage/chemical synthesis/*chemistry/*pharmacologyRNA, Messenger/genetics/metabolismSimplexvirus/*physiologyTumor Necrosis Factor-alpha/antagonists & inhibitors/biosynthesis/*metabolism
DOI
10.1016/j.ejphar.2011.01.062
PMID
21315710
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Dermatology
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
이, 은소손, 성향
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