Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-κB in mouse macrophages

Ai Hsiang Lo, Yu Chih Liang, Shoei Yn Lin-Shiau, Chi Tang Ho, Jen Kun Lin

Research output: Contribution to journalArticle

199 Citations (Scopus)

Abstract

Carnosol is a naturally occurring phytopolyphenol found in rosemary. Carnosol functions as antioxidant and anticarcinogen. In the present study, we compared the antioxidant activity of carnosol and other compounds extracted from rosemary. Carnosol showed potent antioxidative activity in α,α-diphenyl-β-picrylhydrazyl (DPPH) free radicals scavenge and DNA protection from Fenton reaction. High concentrations of nitric oxide (NO) are produced by inducible NO synthase (iNOS) in inflammation and multiple stages of carcinogenesis. Treatment of mouse macrophage RAW 264.7 cell line with carnosol markly reduced lipopolysaccharide (LPS)-stimulated NO production in a concentration-related manner with an IC50 of 9.4 μM; but other tested compounds had slight effects. Western blot, reverse transcription-polymerase chain reaction, and northern blot analyses demonstrated that carnosol decreased LPS-induced iNOS mRNA and protein expression. Carnosol treatment showed reduction of nuclear factor-κB (NF-κB) subunits translocation and NF-κB DNA binding activity in activated macrophages. Carnosol also showed inhibition of iNOS and NF-κB promoter activity in transient transfection assay. These activities were referred to down-regulation of inhibitor κB (IκB) kinase (IKK) activity by carnosol (5 μM), thus inhibited LPS-induced phosphorylation as well as degradation of IκBα. Carnosol also inhibited LPS-induced p38 and p44/42 mitogen-activated protein kinase (MAPK) activation at a higher concentration (20 μM). These results suggest that carnosol suppresses the NO production and iNOS gene expression by inhibiting NF-κB activation, and provide possible mechanisms for its anti-inflammatory and chemopreventive action.

Original languageEnglish
Pages (from-to)983-991
Number of pages9
JournalCarcinogenesis
Volume23
Issue number6
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type II
Antioxidants
Macrophages
Lipopolysaccharides
Nitric Oxide Synthase
Nitric Oxide
carnosol
Anticarcinogenic Agents
DNA
Mitogen-Activated Protein Kinases
Northern Blotting
Inhibitory Concentration 50
Reverse Transcription
Free Radicals
Transfection
Carcinogenesis
Anti-Inflammatory Agents
Phosphotransferases
Down-Regulation
Western Blotting

ASJC Scopus subject areas

  • Cancer Research

Cite this

Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-κB in mouse macrophages. / Lo, Ai Hsiang; Liang, Yu Chih; Lin-Shiau, Shoei Yn; Ho, Chi Tang; Lin, Jen Kun.

In: Carcinogenesis, Vol. 23, No. 6, 2002, p. 983-991.

Research output: Contribution to journalArticle

@article{6172b4b1f37e4ccf94e41f96f684327a,
title = "Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-κB in mouse macrophages",
abstract = "Carnosol is a naturally occurring phytopolyphenol found in rosemary. Carnosol functions as antioxidant and anticarcinogen. In the present study, we compared the antioxidant activity of carnosol and other compounds extracted from rosemary. Carnosol showed potent antioxidative activity in α,α-diphenyl-β-picrylhydrazyl (DPPH) free radicals scavenge and DNA protection from Fenton reaction. High concentrations of nitric oxide (NO) are produced by inducible NO synthase (iNOS) in inflammation and multiple stages of carcinogenesis. Treatment of mouse macrophage RAW 264.7 cell line with carnosol markly reduced lipopolysaccharide (LPS)-stimulated NO production in a concentration-related manner with an IC50 of 9.4 μM; but other tested compounds had slight effects. Western blot, reverse transcription-polymerase chain reaction, and northern blot analyses demonstrated that carnosol decreased LPS-induced iNOS mRNA and protein expression. Carnosol treatment showed reduction of nuclear factor-κB (NF-κB) subunits translocation and NF-κB DNA binding activity in activated macrophages. Carnosol also showed inhibition of iNOS and NF-κB promoter activity in transient transfection assay. These activities were referred to down-regulation of inhibitor κB (IκB) kinase (IKK) activity by carnosol (5 μM), thus inhibited LPS-induced phosphorylation as well as degradation of IκBα. Carnosol also inhibited LPS-induced p38 and p44/42 mitogen-activated protein kinase (MAPK) activation at a higher concentration (20 μM). These results suggest that carnosol suppresses the NO production and iNOS gene expression by inhibiting NF-κB activation, and provide possible mechanisms for its anti-inflammatory and chemopreventive action.",
author = "Lo, {Ai Hsiang} and Liang, {Yu Chih} and Lin-Shiau, {Shoei Yn} and Ho, {Chi Tang} and Lin, {Jen Kun}",
year = "2002",
language = "English",
volume = "23",
pages = "983--991",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-κB in mouse macrophages

AU - Lo, Ai Hsiang

AU - Liang, Yu Chih

AU - Lin-Shiau, Shoei Yn

AU - Ho, Chi Tang

AU - Lin, Jen Kun

PY - 2002

Y1 - 2002

N2 - Carnosol is a naturally occurring phytopolyphenol found in rosemary. Carnosol functions as antioxidant and anticarcinogen. In the present study, we compared the antioxidant activity of carnosol and other compounds extracted from rosemary. Carnosol showed potent antioxidative activity in α,α-diphenyl-β-picrylhydrazyl (DPPH) free radicals scavenge and DNA protection from Fenton reaction. High concentrations of nitric oxide (NO) are produced by inducible NO synthase (iNOS) in inflammation and multiple stages of carcinogenesis. Treatment of mouse macrophage RAW 264.7 cell line with carnosol markly reduced lipopolysaccharide (LPS)-stimulated NO production in a concentration-related manner with an IC50 of 9.4 μM; but other tested compounds had slight effects. Western blot, reverse transcription-polymerase chain reaction, and northern blot analyses demonstrated that carnosol decreased LPS-induced iNOS mRNA and protein expression. Carnosol treatment showed reduction of nuclear factor-κB (NF-κB) subunits translocation and NF-κB DNA binding activity in activated macrophages. Carnosol also showed inhibition of iNOS and NF-κB promoter activity in transient transfection assay. These activities were referred to down-regulation of inhibitor κB (IκB) kinase (IKK) activity by carnosol (5 μM), thus inhibited LPS-induced phosphorylation as well as degradation of IκBα. Carnosol also inhibited LPS-induced p38 and p44/42 mitogen-activated protein kinase (MAPK) activation at a higher concentration (20 μM). These results suggest that carnosol suppresses the NO production and iNOS gene expression by inhibiting NF-κB activation, and provide possible mechanisms for its anti-inflammatory and chemopreventive action.

AB - Carnosol is a naturally occurring phytopolyphenol found in rosemary. Carnosol functions as antioxidant and anticarcinogen. In the present study, we compared the antioxidant activity of carnosol and other compounds extracted from rosemary. Carnosol showed potent antioxidative activity in α,α-diphenyl-β-picrylhydrazyl (DPPH) free radicals scavenge and DNA protection from Fenton reaction. High concentrations of nitric oxide (NO) are produced by inducible NO synthase (iNOS) in inflammation and multiple stages of carcinogenesis. Treatment of mouse macrophage RAW 264.7 cell line with carnosol markly reduced lipopolysaccharide (LPS)-stimulated NO production in a concentration-related manner with an IC50 of 9.4 μM; but other tested compounds had slight effects. Western blot, reverse transcription-polymerase chain reaction, and northern blot analyses demonstrated that carnosol decreased LPS-induced iNOS mRNA and protein expression. Carnosol treatment showed reduction of nuclear factor-κB (NF-κB) subunits translocation and NF-κB DNA binding activity in activated macrophages. Carnosol also showed inhibition of iNOS and NF-κB promoter activity in transient transfection assay. These activities were referred to down-regulation of inhibitor κB (IκB) kinase (IKK) activity by carnosol (5 μM), thus inhibited LPS-induced phosphorylation as well as degradation of IκBα. Carnosol also inhibited LPS-induced p38 and p44/42 mitogen-activated protein kinase (MAPK) activation at a higher concentration (20 μM). These results suggest that carnosol suppresses the NO production and iNOS gene expression by inhibiting NF-κB activation, and provide possible mechanisms for its anti-inflammatory and chemopreventive action.

UR - http://www.scopus.com/inward/record.url?scp=0036316905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036316905&partnerID=8YFLogxK

M3 - Article

C2 - 12082020

AN - SCOPUS:0036316905

VL - 23

SP - 983

EP - 991

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 6

ER -