Effects of sesquiterpenes and amino acid-sesquiterpene conjugates from the roots of Saussurea lappa on inducible nitric oxide synthase and heat shock protein in lipopolysaccharide-activated macrophages

Hisashi Matsuda; Iwao Toguchida; Kiyofumi Ninomiya; Tadashi Kageura; Toshio Morikawa; Masayuki Yoshikawa

doi:10.1016/s0968-0896(02)00471-6

Effects of sesquiterpenes and amino acid-sesquiterpene conjugates from the roots of Saussurea lappa on inducible nitric oxide synthase and heat shock protein in lipopolysaccharide-activated macrophages

Bioorg Med Chem. 2003 Mar 6;11(5):709-15. doi: 10.1016/s0968-0896(02)00471-6.

Authors

Hisashi Matsuda¹, Iwao Toguchida, Kiyofumi Ninomiya, Tadashi Kageura, Toshio Morikawa, Masayuki Yoshikawa

Affiliation

¹ Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, 607-8412, Kyoto, Japan.

PMID: 12538000
DOI: 10.1016/s0968-0896(02)00471-6

Abstract

The methanolic extract of the roots of Saussurea lappa CLARKE, a Chinese medicinal herb Saussureae Radix, was found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages. Among the constituents from the methanolic extract, two sesquiterpene lactones (costunolide and dehydrocostus lactone) and two amino acid-sesquiterpene conjugates (saussureamines A and B) potently inhibited LPS-induced NO production (IC(50)=1.2-2.8 microM). Saussureamines A and B in addition to costunolide and dehydrocostus lactone did not inhibit iNOS enzyme activity, but they inhibited both induction of inducible NO synthase and activation of nuclear factor-kappaB in accordance with induction of heat shock protein 72.

MeSH terms

Algorithms
Amino Acids / isolation & purification
Amino Acids / pharmacology*
Animals
Electrophoretic Mobility Shift Assay
Enzyme Induction / drug effects
HSP72 Heat-Shock Proteins
Heat-Shock Proteins / biosynthesis*
In Vitro Techniques
Indicators and Reagents
Lipopolysaccharides / pharmacology*
Macrophage Activation / drug effects
Macrophages / drug effects
Macrophages / enzymology
Macrophages / metabolism*
Mice
NF-kappa B / drug effects
Nitric Oxide / biosynthesis
Nitric Oxide Synthase / antagonists & inhibitors*
Nitric Oxide Synthase Type II
Plant Roots / chemistry
Saussurea / chemistry*
Sesquiterpenes / isolation & purification
Sesquiterpenes / pharmacology*
Structure-Activity Relationship

Substances

Amino Acids
HSP72 Heat-Shock Proteins
Heat-Shock Proteins
Indicators and Reagents
Lipopolysaccharides
NF-kappa B
Sesquiterpenes
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nos2 protein, mouse