Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages: structure-activity relationship and molecular mechanisms involved
- PMID: 15963474
- DOI: 10.1016/j.bcp.2005.05.003
Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages: structure-activity relationship and molecular mechanisms involved
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.
Similar articles
-
Green tea proanthocyanidins inhibit cyclooxygenase-2 expression in LPS-activated mouse macrophages: molecular mechanisms and structure-activity relationship.Arch Biochem Biophys. 2007 Apr 1;460(1):67-74. doi: 10.1016/j.abb.2007.01.009. Epub 2007 Jan 29. Arch Biochem Biophys. 2007. PMID: 17313938
-
Dipyridamole activation of mitogen-activated protein kinase phosphatase-1 mediates inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells.Eur J Pharmacol. 2006 Jul 17;541(3):138-46. doi: 10.1016/j.ejphar.2006.05.002. Eur J Pharmacol. 2006. PMID: 16765938
-
Inhibition of lipopolysaccharide-induced cyclooxygenase-2 transcription by 6-(methylsulfinyl) hexyl isothiocyanate, a chemopreventive compound from Wasabia japonica (Miq.) Matsumura, in mouse macrophages.Biochem Pharmacol. 2005 Dec 5;70(12):1772-84. doi: 10.1016/j.bcp.2005.09.023. Epub 2005 Oct 27. Biochem Pharmacol. 2005. PMID: 16256955
-
Signal transduction pathways regulating cyclooxygenase-2 expression: potential molecular targets for chemoprevention.Biochem Pharmacol. 2004 Sep 15;68(6):1089-100. doi: 10.1016/j.bcp.2004.05.031. Biochem Pharmacol. 2004. PMID: 15313405 Review.
-
Aspirin and other cyclooxygenase inhibitors: new therapeutic insights.Semin Vasc Med. 2003 May;3(2):107-12. doi: 10.1055/s-2003-40668. Semin Vasc Med. 2003. PMID: 15199473 Review.
Cited by
-
Malvidin and Its Mono- and Di-Glucosides Forms: A Study of Combining Both In Vitro and Molecular Docking Studies Focused on Cholinesterase, Butyrylcholinesterase, COX-1 and COX-2 Activities.Molecules. 2023 Nov 30;28(23):7872. doi: 10.3390/molecules28237872. Molecules. 2023. PMID: 38067599 Free PMC article.
-
Blackcurrant Anthocyanins Improve Blood Lipids and Biomarkers of Inflammation and Oxidative Stress in Healthy Women in Menopause Transition without Changing Body Composition.Biomedicines. 2023 Oct 19;11(10):2834. doi: 10.3390/biomedicines11102834. Biomedicines. 2023. PMID: 37893207 Free PMC article.
-
Anthocyanins as Immunomodulatory Dietary Supplements: A Nutraceutical Perspective and Micro-/Nano-Strategies for Enhanced Bioavailability.Nutrients. 2023 Sep 26;15(19):4152. doi: 10.3390/nu15194152. Nutrients. 2023. PMID: 37836436 Free PMC article. Review.
-
Unleashing nature's potential and limitations: Exploring molecular targeted pathways and safe alternatives for the treatment of multiple sclerosis (Review).Med Int (Lond). 2023 Aug 17;3(5):42. doi: 10.3892/mi.2023.102. eCollection 2023 Sep-Oct. Med Int (Lond). 2023. PMID: 37680650 Free PMC article. Review.
-
Kinetic Ultrasound-Assisted Extraction as a Sustainable Approach for the Recovery of Phenolics Accumulated through UVA Treatment in Strawberry By-Products.Foods. 2023 Aug 8;12(16):2989. doi: 10.3390/foods12162989. Foods. 2023. PMID: 37627988 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous