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Cited by 231Phytochemicals and Antioxidant ActivitiesInflammatory mediators and NSAID effectsNatural Compounds in Disease Treatment

Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages: structure-activity relationship and molecular mechanisms involved

Hou, De-Xing, Yanagita, Takashi, Uto, Takuhiro, Masuzaki, Satoko, Fujii, Makoto·2005·Biochemical Pharmacology
DOI 10.1016/j.bcp.2005.05.003
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Abstract

The effects of anthocyanidins, the aglycon nucleuses of anthocyanins widely occurring in reddish fruits and vegetables, on the expression of cyclooxygenase-2 (COX-2) were investigated in lipopolysaccharide (LPS)-activated murine macrophage RAW264 cells. Of five anthocyanidins, delphinidin and cyanidin inhibited LPS-induced COX-2 expression, but pelargonidin, peonidin and malvidin did not. The structure-activity relationship suggest that the ortho-dihydroxyphenyl structure of anthocyanidins on the B-ring appears to be related with the inhibitory actions. Delphinidin, the most potent inhibitor, caused a dose-dependent inhibition of COX-2 expression at both mRNA and protein levels. Western blotting analysis indicated that delphinidin inhibited the degradation of IkappaB-alpha, nuclear translocation of p65 and CCAAT/enhancer-binding protein (C/EBP)delta and phosphorylation of c-Jun, but not CRE-binding protein (CREB). Moreover, delphinidin suppressed the activations of mitogen-activated protein kinase (MAPK) including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 kinase. MAPK inhibitors (U0126 for MEK1/2, SB203580 for p38 kinase and SP600125 for JNK) specifically blocked LPS-induced COX-2 expression. Thus, our results demonstrated that LPS-induced COX-2 expression by activating MAPK pathways and delphinidin suppressed COX-2 by blocking MAPK-mediated pathways with the attendant activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and C/EBPdelta. These findings provide the first molecular basis that anthocyanidins with ortho-dihydroxyphenyl structure may have anti-inflammatory properties through the inhibition of MAPK-mediated COX-2 expression.

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  • LPS activates three subclasses of MAPKs in macrophages and other cells: ERK, JNK, and p38; some compounds suppress proinflammatory cytokines and NF-κB and inhibit COX-2 and iNOS expression by inhibiting some of these MAPKs.

    “In macrophages and other types of cells, LPS activates three subclasses of MAPKs: extracellular signal-regulated kinase (ERK), c-Jun-terminal kinase (JNK) and p38. Studies have revealed that some compounds are able to suppress proinflammatory cytokines and NF-κB, to inhibit the COX-2 and iNOS expression inhibiting some of these MAPKS [129,130,131].”

    From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [131]

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Authors
Hou, D.-X., Yanagita, T., Uto, T., Masuzaki, S., & Fujii, M.
Affiliations
Kagoshima University (JP)
Corresponding author
Hou, De-Xing
ORCID
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2005-08
Volume
70
Issue
3
Pages
417-425
ISSN
0006-2952 (ISSN-L)
DOI
10.1016/j.bcp.2005.05.003
OpenAlex
W1992658935
Cited by
231
References
41
Citations by year
2026: 6 · 2025: 11 · 2024: 9 · 2023: 12 · 2022: 11 · 2021: 14 · 2020: 7 · 2019: 9 · 2018: 9 · 2017: 12 · 2016: 13 · 2015: 16 · 2014: 14 · 2013: 16 · 2012: 7
FWCI
5.90
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology (13660130)
  • Kagoshima University
Topics
  • Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
  • Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
Keywords
anthocyanidins, cyclooxygenase-2, delphinidin, cyanidin, lipopolysaccharide, macrophages, structure-activity relationship, NF-κB, MAPK signaling, JNK, ERK, p38 MAPK, AP-1, C/EBPδ, anti-inflammatory activity
MeSH terms
Animals, Anthocyanins, Cell Line, Lipopolysaccharides, Macrophages, Prostaglandin-Endoperoxide Synthases, Structure-Activity Relationship, Transcription, Genetic, Gene Expression Regulation, Enzymologic, Cyclooxygenase Inhibitors, Mitogen-Activated Protein Kinases, Protein Kinase Inhibitors, Mice, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors

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