Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-kappaB signaling

Yu Wen Cheng, Ching Yi Chang, Kou Lung Lin, Chien Ming Hu, Cheng Hui Lin, Jaw Jou Kang

Research output: Contribution to journalArticle

Abstract

AIM OF THE STUDY: Shikonin/alkannin (SA) derivatives, analogs of naphthoquinone pigments, are the major components of root extracts of the Chinese medicinal herb (Lithospermum erythrorhizon; LE) and widely distributed in several folk medicines. In the present study, the effect and the underline molecular mechanism of shikonin derivatives isolated from root extracts of Lithospermum euchroma on lipopolysaccharide (LPS)-induced inflammatory response were investigated.

MATERIALS AND METHODS: Effects of five SA derivatives, including SA, acetylshikonin, beta,beta-dimethylacrylshikonin, 5,8-dihydroxy-1.4-naphthoquinone, and 1,4-naphthoquinone on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in mouse macrophage RAW264.7 cells were examined.

RESULTS: Data suggested that SA derivatives inhibited LPS-induced NO and PGE(2) production, and iNOS protein expression. RT-PCR analysis showed that SA derivatives diminished LPS-induced iNOS mRNA expression. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in LPS-stimulated RAW 264.7 cells was concentration-dependently suppressed by SA derivatives. SA inhibited NF-kappaB activation by prevention of the degradation of inhibitory factor-kappaB and p65 level in nuclear fractions induced by LPS.

CONCLUSIONS: Taken together, these results suggest that the anti-inflammatory properties of SA derivatives might result from inhibition of iNOS protein expression through the downregulation of NF-kappaB activation via suppression of phosphorylation of ERK, in LPS-stimulated RAW 264.7 cells.

Original languageEnglish
Pages (from-to)264-71
Number of pages8
JournalJournal of Ethnopharmacology
Volume120
Issue number2
DOIs
Publication statusPublished - Nov 20 2008

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NF-kappa B
Lipopolysaccharides
Down-Regulation
Lithospermum
Naphthoquinones
Nitric Oxide
Phosphorylation
RAW 264.7 Cells
shikonin
Mitogen-Activated Protein Kinase 3
alkannin
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
Traditional Medicine
Medicinal Plants
Prostaglandins E
Dinoprostone
Proteins
Anti-Inflammatory Agents
Macrophages

Keywords

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cell Line
  • Dinoprostone
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Lipopolysaccharides
  • Lithospermum
  • Macrophages
  • Mice
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • NF-kappa B
  • Naphthoquinones
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Phosphorylation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-kappaB signaling. / Cheng, Yu Wen; Chang, Ching Yi; Lin, Kou Lung; Hu, Chien Ming; Lin, Cheng Hui; Kang, Jaw Jou.

In: Journal of Ethnopharmacology, Vol. 120, No. 2, 20.11.2008, p. 264-71.

Research output: Contribution to journalArticle

Cheng, Yu Wen ; Chang, Ching Yi ; Lin, Kou Lung ; Hu, Chien Ming ; Lin, Cheng Hui ; Kang, Jaw Jou. / Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-kappaB signaling. In: Journal of Ethnopharmacology. 2008 ; Vol. 120, No. 2. pp. 264-71.
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abstract = "AIM OF THE STUDY: Shikonin/alkannin (SA) derivatives, analogs of naphthoquinone pigments, are the major components of root extracts of the Chinese medicinal herb (Lithospermum erythrorhizon; LE) and widely distributed in several folk medicines. In the present study, the effect and the underline molecular mechanism of shikonin derivatives isolated from root extracts of Lithospermum euchroma on lipopolysaccharide (LPS)-induced inflammatory response were investigated.MATERIALS AND METHODS: Effects of five SA derivatives, including SA, acetylshikonin, beta,beta-dimethylacrylshikonin, 5,8-dihydroxy-1.4-naphthoquinone, and 1,4-naphthoquinone on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in mouse macrophage RAW264.7 cells were examined.RESULTS: Data suggested that SA derivatives inhibited LPS-induced NO and PGE(2) production, and iNOS protein expression. RT-PCR analysis showed that SA derivatives diminished LPS-induced iNOS mRNA expression. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in LPS-stimulated RAW 264.7 cells was concentration-dependently suppressed by SA derivatives. SA inhibited NF-kappaB activation by prevention of the degradation of inhibitory factor-kappaB and p65 level in nuclear fractions induced by LPS.CONCLUSIONS: Taken together, these results suggest that the anti-inflammatory properties of SA derivatives might result from inhibition of iNOS protein expression through the downregulation of NF-kappaB activation via suppression of phosphorylation of ERK, in LPS-stimulated RAW 264.7 cells.",
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TY - JOUR

T1 - Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-kappaB signaling

AU - Cheng, Yu Wen

AU - Chang, Ching Yi

AU - Lin, Kou Lung

AU - Hu, Chien Ming

AU - Lin, Cheng Hui

AU - Kang, Jaw Jou

PY - 2008/11/20

Y1 - 2008/11/20

N2 - AIM OF THE STUDY: Shikonin/alkannin (SA) derivatives, analogs of naphthoquinone pigments, are the major components of root extracts of the Chinese medicinal herb (Lithospermum erythrorhizon; LE) and widely distributed in several folk medicines. In the present study, the effect and the underline molecular mechanism of shikonin derivatives isolated from root extracts of Lithospermum euchroma on lipopolysaccharide (LPS)-induced inflammatory response were investigated.MATERIALS AND METHODS: Effects of five SA derivatives, including SA, acetylshikonin, beta,beta-dimethylacrylshikonin, 5,8-dihydroxy-1.4-naphthoquinone, and 1,4-naphthoquinone on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in mouse macrophage RAW264.7 cells were examined.RESULTS: Data suggested that SA derivatives inhibited LPS-induced NO and PGE(2) production, and iNOS protein expression. RT-PCR analysis showed that SA derivatives diminished LPS-induced iNOS mRNA expression. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in LPS-stimulated RAW 264.7 cells was concentration-dependently suppressed by SA derivatives. SA inhibited NF-kappaB activation by prevention of the degradation of inhibitory factor-kappaB and p65 level in nuclear fractions induced by LPS.CONCLUSIONS: Taken together, these results suggest that the anti-inflammatory properties of SA derivatives might result from inhibition of iNOS protein expression through the downregulation of NF-kappaB activation via suppression of phosphorylation of ERK, in LPS-stimulated RAW 264.7 cells.

AB - AIM OF THE STUDY: Shikonin/alkannin (SA) derivatives, analogs of naphthoquinone pigments, are the major components of root extracts of the Chinese medicinal herb (Lithospermum erythrorhizon; LE) and widely distributed in several folk medicines. In the present study, the effect and the underline molecular mechanism of shikonin derivatives isolated from root extracts of Lithospermum euchroma on lipopolysaccharide (LPS)-induced inflammatory response were investigated.MATERIALS AND METHODS: Effects of five SA derivatives, including SA, acetylshikonin, beta,beta-dimethylacrylshikonin, 5,8-dihydroxy-1.4-naphthoquinone, and 1,4-naphthoquinone on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in mouse macrophage RAW264.7 cells were examined.RESULTS: Data suggested that SA derivatives inhibited LPS-induced NO and PGE(2) production, and iNOS protein expression. RT-PCR analysis showed that SA derivatives diminished LPS-induced iNOS mRNA expression. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in LPS-stimulated RAW 264.7 cells was concentration-dependently suppressed by SA derivatives. SA inhibited NF-kappaB activation by prevention of the degradation of inhibitory factor-kappaB and p65 level in nuclear fractions induced by LPS.CONCLUSIONS: Taken together, these results suggest that the anti-inflammatory properties of SA derivatives might result from inhibition of iNOS protein expression through the downregulation of NF-kappaB activation via suppression of phosphorylation of ERK, in LPS-stimulated RAW 264.7 cells.

KW - Animals

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Cell Line

KW - Dinoprostone

KW - Dose-Response Relationship, Drug

KW - Down-Regulation

KW - Lipopolysaccharides

KW - Lithospermum

KW - Macrophages

KW - Mice

KW - Mitogen-Activated Protein Kinase 1

KW - Mitogen-Activated Protein Kinase 3

KW - NF-kappa B

KW - Naphthoquinones

KW - Nitric Oxide

KW - Nitric Oxide Synthase Type II

KW - Phosphorylation

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jep.2008.09.002

DO - 10.1016/j.jep.2008.09.002

M3 - Article

C2 - 18835347

VL - 120

SP - 264

EP - 271

JO - Journal of Ethnopharmacology

JF - Journal of Ethnopharmacology

SN - 0378-8741

IS - 2

ER -