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  • Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes.

Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes.

BMC complementary and alternative medicine (2015-04-19)
Shao-Ju Chien, Te-Chuan Chen, Hsing-Chun Kuo, Cheng-Nan Chen, Shun-Fu Chang
ABSTRACT

Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases. Fulvic acid (FA), a class of compounds of humic substances, possesses various pharmacological properties. However, the effect of FA on inflammatory responses of the monocytes remains unclear. We investigated the regulatory effect of FA on homocysteine-induced COX-2 expression in human monocytes. Peripheral blood monocytes and U937 cells were used for all experiments. Real-time PCR and ELISA assay were used to analyze the COX-2 mRNA expression and PGE2 secretion, respectively. Specific inhibitors were used to investigate the mechanism of homocysteine-mediating COX-2 mRNA expression and PGE2 secretion. Luciferase assay, transcription factor ELISA, and chromatin immunoprecipitation were used to determine the role of nuclear factor-κB in FA-mediated inhibition of homocysteine effect on monocytes. The results show that pretreating monocytes with FA inhibited the homocysteine-induced COX-2 expression in a dose-dependent manner. Stimulation of U937 monocytes with homocysteine induced rapid increases in the phosphorylation of ERK and JNK; the inhibitor for ERK and JNK attenuated the homocysteine-induced nuclear factor-κB activation and COX-2 expression. Transcription factor ELISA and chromatin immunoprecipitation assays showed that FA blocked the homocysteine-induced increases in the binding activity and in vivo promoter binding of nuclear factor-κB in monocytes. Our findings provide a molecular mechanism by which FA inhibits homocysteine-induced COX-2 expression in monocytes, and a basis for using FA in pharmaceutical therapy against inflammation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Pyrrolidine, ≥99.0%
Sigma-Aldrich
Prostaglandin E2, synthetic, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Prostaglandin E2, ≥93% (HPLC), synthetic
Sigma-Aldrich
Prostaglandin E2, γ-irradiated, powder, BioXtra, suitable for cell culture
Sigma-Aldrich
Pyrrolidine, ≥99.5%, purified by redistillation
Sigma-Aldrich
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Sigma-Aldrich
Pyrrolidine, 99%
Dinoprostone, European Pharmacopoeia (EP) Reference Standard