Synthesized pyridine compound derivatives decreased TNF alpha and adhesion molecules and ameliorated HSV-induced inflammation in a mouse model
Copyright policy )Synthesized pyridine compound derivatives decreased TNF alpha and adhesion molecules and ameliorated HSV-induced inflammation in a mouse model
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.
- Ajou University Korea (Republic of)
- Yonsei University Medical Library Korea (Republic of)
- Yonsei University Health System Korea (Republic of)
- Yonsei University Korea (Republic of)
Male, Pyridines, Down-Regulation/drug effects, Administration, Oral, Messenger/metabolism, Herpes simplex virus, Behcet Syndrome/genetics, Naphthyridines/chemistry, Tumor Necrosis Factor-alpha/metabolism*, Mice, Simplexvirus, Pyridines/administration & dosage, Pyridines/pharmacology*, Naphthyridines/administration & dosage, Naphthyridines/chemical synthesis, Pyridine compound derivative, Behcet Syndrome, Behcet Syndrome/metabolism*, Administration, Cell Adhesion Molecules/genetics, Behcet Syndrome/virology*, Oral, Naphthyridines/pharmacology, Cell Adhesion Molecules/metabolism*, Simplexvirus/physiology*, Tumor Necrosis Factor-alpha/biosynthesis, 610, Down-Regulation, Mouse model, Cell Line, Anti-inflammation, Behcet Syndrome/drug therapy, Animals, Humans, Pyridines/chemical synthesis, RNA, Messenger, Naphthyridines, Pyridines/chemistry*, Animal, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Tumor Necrosis Factor-alpha, Behcet's disease, Oral administration, Molecular Weight, Disease Models, Animal, Disease Models, RNA, Messenger/genetics, TNF alpha, Cell Adhesion Molecules
Male, Pyridines, Down-Regulation/drug effects, Administration, Oral, Messenger/metabolism, Herpes simplex virus, Behcet Syndrome/genetics, Naphthyridines/chemistry, Tumor Necrosis Factor-alpha/metabolism*, Mice, Simplexvirus, Pyridines/administration & dosage, Pyridines/pharmacology*, Naphthyridines/administration & dosage, Naphthyridines/chemical synthesis, Pyridine compound derivative, Behcet Syndrome, Behcet Syndrome/metabolism*, Administration, Cell Adhesion Molecules/genetics, Behcet Syndrome/virology*, Oral, Naphthyridines/pharmacology, Cell Adhesion Molecules/metabolism*, Simplexvirus/physiology*, Tumor Necrosis Factor-alpha/biosynthesis, 610, Down-Regulation, Mouse model, Cell Line, Anti-inflammation, Behcet Syndrome/drug therapy, Animals, Humans, Pyridines/chemical synthesis, RNA, Messenger, Naphthyridines, Pyridines/chemistry*, Animal, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Tumor Necrosis Factor-alpha, Behcet's disease, Oral administration, Molecular Weight, Disease Models, Animal, Disease Models, RNA, Messenger/genetics, TNF alpha, Cell Adhesion Molecules
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