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Suppressive effects of methoxyflavonoids isolated from Kaempferia parviflora on inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells.

AbstractETHNOPHARMACOLOGICAL RELEVANCE:
The rhizomes of Kaempferia parviflora Wall. ex Baker have been traditionally used in Thailand to treat abscesses, gout, and peptic ulcers.
AIM:
Previously, we reported that the chloroform fraction of a Kaempferia parviflora extract had an inhibitory effect on rat paw-edema. In the present study, we isolated the constituents of this fraction and investigated the anti-inflammatory mechanism against nitric oxide (NO) production, tumor necrosis factor-α (TNF-α) and the expression of inducible nitric oxide synthase (iNOS) as well as phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated c-Jun N-terminal kinase (p-JNK). In addition, effects of trimethylapigenin (4) on the enzyme activities of protein kinases possibly leading to iNOS expression were examined to clarify the targets.
MATERIALS AND METHODS:
The chloroform fraction was isolated using silica gel column chromatography and HPLC. Isolated compounds were tested against NO and TNF-α using RAW264.7 cells. Cytotoxicity and iNOS, p-ERK and p-JNK expression were also examined.
RESULTS:
Three active components, 5,7-dimethoxyflavone (2), trimethylapigenin (4), and tetramethylluteolin (5), markedly inhibited the production of NO in lipopolysaccharide (LPS)-activated RAW264.7 cells. Compounds 2, 4, and 5 moderately inhibited production of TNF-α. Compounds 2, 4, and 5 strongly inhibited expression of iNOS mRNA and iNOS protein in a dose-dependent manner, but did not inhibit p-ERK or p-JNK protein expression. The most active compound, 4, did not inhibit the enzyme activity of inhibitor of κB kinases or mitogen-activated protein kinases, but inhibited that of spleen tyrosine kinase (SYK).
CONCLUSION:
The mechanism responsible for the anti-inflammatory activity of methoxyflavonoids from the chloroform fraction of the rhizomes of Kaempferia parviflora is mainly the inhibition of iNOS expression, and the inhibition of SYK by 4 may be involved in the suppression of LPS-induced signaling in macrophages.
AuthorsChutha Sae-Wong, Hisashi Matsuda, Supinya Tewtrakul, Pimpimon Tansakul, Seikou Nakamura, Yukiko Nomura, Masayuki Yoshikawa
JournalJournal of ethnopharmacology (J Ethnopharmacol) Vol. 136 Issue 3 Pg. 488-95 (Jul 14 2011) ISSN: 1872-7573 [Electronic] Ireland
PMID21251970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents
  • Flavones
  • Flavonoids
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Plant Extracts
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • 5,7-dimethoxyflavone
  • Nitric Oxide
  • Apigenin
  • Nitric Oxide Synthase Type II
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse
  • Syk protein, rat
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Luteolin
Topics
  • Animals
  • Anti-Inflammatory Agents (isolation & purification, pharmacology, therapeutic use)
  • Apigenin (isolation & purification, pharmacology, therapeutic use)
  • Cell Line
  • Dose-Response Relationship, Drug
  • Extracellular Signal-Regulated MAP Kinases (metabolism)
  • Flavones (isolation & purification, pharmacology, therapeutic use)
  • Flavonoids (isolation & purification, pharmacology, therapeutic use)
  • Inflammation (drug therapy, metabolism)
  • Intracellular Signaling Peptides and Proteins (antagonists & inhibitors)
  • JNK Mitogen-Activated Protein Kinases (metabolism)
  • Lipopolysaccharides
  • Luteolin (isolation & purification, pharmacology, therapeutic use)
  • Macrophages (drug effects, metabolism)
  • Mice
  • Nitric Oxide (biosynthesis)
  • Nitric Oxide Synthase Type II (genetics, metabolism)
  • Phytotherapy
  • Plant Extracts (chemistry, pharmacology, therapeutic use)
  • Protein-Tyrosine Kinases (antagonists & inhibitors)
  • RNA, Messenger (metabolism)
  • Rhizome
  • Syk Kinase
  • Tumor Necrosis Factor-alpha (metabolism)
  • Zingiberaceae (chemistry)

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