Antagonistic effects of acetylshikonin on LPS-induced NO and PGE(2) production in BV2 microglial cells via inhibition of ROS/PI3K/Akt-mediated NF-kappa B signaling and activation of Nrf2-dependent HO-1
- Authors
- Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Lee, Kyoung-Tae; Choi, Yung Hyun; Moon, Sung-Kwon; Kim, Wun-Jae; Kim, Gi-Young
- Issue Date
- Oct-2015
- Publisher
- SPRINGER
- Keywords
- Acetylshikonin; Nitric oxide; Prostaglandin E-2; Nuclear factor-kappa B; Heme oxygenase-1; Nuclear factor-erythroid 2-related factor 2
- Citation
- IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, v.51, no.9, pp 975 - 986
- Pages
- 12
- Journal Title
- IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
- Volume
- 51
- Number
- 9
- Start Page
- 975
- End Page
- 986
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/9054
- DOI
- 10.1007/s11626-015-9922-y
- ISSN
- 1071-2690
1543-706X
- Abstract
- Although acetylshikonin (ACS) is known to have antioxidant and antitumor activities, whether ACS regulates the expression of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated microglial cells remains unclear. In this study, it was found that ACS isolated from Lithospermum erythrorhizon inhibits LPS-induced nitric oxide (NO) and prostaglandin E-2 (PGE(2)) release by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in BV2 microglial cells. Furthermore, ACS reduced the LPS-induced DNA-binding activity of nuclear factor-kappa B (NF-kappa B) and subsequently suppressed iNOS and COX-2 expression. Consistent with these data, ACS attenuated the phosphorylation of PI3K and Akt and suppressed the DNA-binding activity of NF-kappa B by inducing the generation of reactive oxygen species (ROS) in LPS-stimulated cells. In addition, ACS enhanced heme oxygenase-1 (HO-1) expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation. Zinc protoporphyrin, a specific HO-1 inhibitor, partially attenuated the antagonistic effects of ACS on LPS-induced NO and PGE(2) production. By contrast, the presence of cobalt protoporphyrin, a specific HO-1 inducer, potently suppressed LPS-induced NO and PGE(2) production. These data indicate that ACS downregulates proinflammatory mediators such as NO and PGE(2) by suppressing PI3K/Akt-dependent NF-kappa B activity induced by ROS as well as inducing Nrf2-dependent HO-1 activity. Taken together, ACS might be a good candidate to regulate LPS-mediated inflammatory diseases.
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