Anti-inflammatory effects of beta-hydroxyisovalerylshikonin in BV2 microglia are mediated through suppression of the PI3K/Akt/NF-kB pathway and activation of the Nrf2/HO-1 pathway

作者：Jayasooriya Rajapaksha Gedara Prasad Tharanga; Lee Kyoung Tae; Lee Hak Ju; Choi Yung Hyun; Jeong Jin Woo; Kim Gi Young^*

来源：Food and Chemical Toxicology, 2014, 65: 82-89.

DOI：10.1016/j.fct.2013.12.011

• beta-Hydroxyisovalerylshikonin
• Nitric oxide
• Prostaglandin E2
• Nuclear factor-kappa B
• Home oxygenase-1
• Nuclear factor-erythroid 2-related factor 2

In the present study, we investigated whether beta-hydroxyisovalerylshikonin (beta-HIVS) affects the production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E-2 (PGE(2)) in BV2 microglial cells. Our data showed that beta-HIVS inhibited secretion of NO and PGE(2) and downregulated expression of their main regulatory genes, inducible NO synthesis (iNOS) and cyclooxygenase-2 (COX-2). beta-HIVS also reduced the LPS-induced DNA-binding activity of nuclear factor-kappa B (NF-kappa B) by suppressing nuclear translocation of the NF-kappa B subunits and inhibiting the degradation and phosphorylation of 1KBot. Furthermore, an NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC), attenuated LPS-stimulated iNOS and COX2 expression, suggesting that NF-kappa B inhibition is a main effector in the expression of iNOS and COX-2. We also found that LPS-induced NF-kappa B activation is regulated through inhibition of P13K/Akt phosphorylation in response to beta-HIVS. Additionally, beta-HIVS caused the induction of heme oxygenase-1 (HO-1) via upregulation of nuclear factor-erythroid 2-related factor 2 (Nrf2), both of which are involved in the secretion of proinflammatory mediators such as NO and PGE(2). Taken together, our data indicate that p-Hivs diminishes the proinflammatory mediators NO and PGE(2) and the expression of their regulatory genes, iNOS and COX-2, in LPS-stimulated BV2 microglial cells by inhibiting P13K/Akt-dependent NF-IcB activation and inducing Nrf2-mediated HO-1 expression.

• 出版日期2014-3