Abstract
We investigated the effect of chikusetsusaponin IVa (CS) and chikusetsusaponin IVa methyl ester (CS-ME) from the roots of Achyranthes japonica NAKAI on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW264.7 macrophages. CS-ME more potently inhibited LPS-induced NO and PGE2 production than CS. CS-ME concentration-dependently inhibited LPS-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 and IL-1β production in RAW264.7 macrophages and mouse peritoneal macrophages. Consistent with these findings, CS-ME suppressed LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 at protein level as well as iNOS, COX-2, TNF-α, IL-6, and IL-1β at mRNA level. In addition, CS-ME suppressed LPS-induced transcriptional activity of nuclear factor (NF)-κB and activator protein (AP)-1. The anti-inflammatory properties of CS-ME might result from suppression of iNOS, COX-2, TNF-α, IL-6, and IL-1β expression through downregulation of NF-κB and AP-1 in macrophages.
MeSH terms
-
Achyranthes*
-
Animals
-
Anti-Inflammatory Agents / isolation & purification
-
Anti-Inflammatory Agents / pharmacology*
-
Cyclooxygenase 2 / genetics
-
Cyclooxygenase 2 / metabolism
-
Dinoprostone / metabolism
-
Esters / isolation & purification
-
Esters / pharmacology*
-
Interleukin-1beta / genetics
-
Interleukin-1beta / metabolism
-
Interleukin-6 / genetics
-
Interleukin-6 / metabolism
-
Lipopolysaccharides
-
Mice
-
NF-kappa B / metabolism
-
Nitric Oxide Synthase Type II / genetics
-
Nitric Oxide Synthase Type II / metabolism
-
Oleanolic Acid / analogs & derivatives*
-
Oleanolic Acid / isolation & purification
-
Oleanolic Acid / pharmacology
-
Plant Roots / chemistry
-
RAW 264.7 Cells
-
Saponins / isolation & purification
-
Saponins / pharmacology*
-
Transcription Factor AP-1 / metabolism
-
Tumor Necrosis Factor-alpha / genetics
-
Tumor Necrosis Factor-alpha / metabolism
Substances
-
Anti-Inflammatory Agents
-
Esters
-
IL1B protein, mouse
-
Interleukin-1beta
-
Interleukin-6
-
Lipopolysaccharides
-
NF-kappa B
-
Saponins
-
Transcription Factor AP-1
-
Tumor Necrosis Factor-alpha
-
chikusetsu saponin IVa
-
Oleanolic Acid
-
Nitric Oxide Synthase Type II
-
Nos2 protein, mouse
-
Ptgs2 protein, mouse
-
Cyclooxygenase 2
-
Dinoprostone