0

Downregulation of NO and PGE2 in LPS-stimulated BV2 Microglial Cells by Trans-Isoferulic Acid via Suppression of PI3K/Akt-dependent NF-κB and Activation of Nrf2-mediated HO-1

Matharage Gayani Dilshara, Kyoung-Tae Lee, Rajapaksha Gedara Prasad Tharanga Jayasooriya, Chang-Hee Kang, Sang Rul Park, Yung Hyun Choi, Il-Whan Choi, Jin-Won Hyun, Weon-Young Chang, Yeon-Su Kim, Hak-Ju Lee, etc.

Int Immunopharmacol. 2014 Jan;18(1):203-11.

PMID: 24291391

Abstract:

Little is known about whether trans-isoferulic acid (TIA) regulates the production of lipopolysaccharide (LPS)-induced proinflammatory mediators. Therefore, we examined the effect of TIA isolated from Clematis mandshurica on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in BV2 microglial cells. We found that TIA inhibited the production of LPS-induced NO and PGE2 without accompanying cytotoxicity in BV2 microglial cells. TIA also downregulated the expression levels of specific regulatory genes such as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) by suppressing LPS-induced NF-κB activity via dephosphorylation of PI3K/Akt. In addition, we demonstrated that a specific NF-κB inhibitor PDTC and a selective PI3K/Akt inhibitor, LY294002 effectively attenuated the expression of LPS-stimulated iNOS and COX-2 mRNA, while LY294002 suppressed LPS-induced NF-κB activity, suggesting that TIA attenuates the expression of these proinflammatory genes by suppressing PI3K/Akt-mediated NF-κB activity. Our results showed that TIA suppressed NO and PGE2 production through the induction of nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent heme oxygenase-1 (HO-1). Taken together, our data indicate that TIA suppresses the production of proinflammatory mediators such as NO and PGE2, as well as their regulatory genes, in LPS-stimulated BV2 microglial cells, by inhibiting PI3K/Akt-dependent NF-κB activity and enhancing Nrf2-mediated HO-1 expression.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP25522332-A trans-Isoferulic acid trans-Isoferulic acid 25522-33-2 Price
qrcode