Shikonin Isolated from Lithospermum erythrorhizon Downregulates Proinflammatory Mediators in Lipopolysaccharide-Stimulated BV2 Microglial Cells by Suppressing Crosstalk between Reactive Oxygen Species and NF-kappaB.
10.4062/biomolther.2015.006
- Author:
Rajapaksha Gedara PRASAD
1
;
Yung Hyun CHOI
;
Gi Young KIM
Author Information
1. Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea. immunkim@jejunu.ac.kr
- Publication Type:Original Article
- Keywords:
Shikonin;
Proinflammatory mediators;
Reactive oxygen species;
Nuclear factor-kappaB
- MeSH:
Cyclooxygenase 2;
Dinoprostone;
Down-Regulation;
Genes, Regulator;
Inflammation;
Lithospermum*;
Neurons;
NF-kappa B*;
Nitric Oxide;
Nitric Oxide Synthase;
Reactive Oxygen Species*;
Social Problems;
Tumor Necrosis Factor-alpha
- From:Biomolecules & Therapeutics
2015;23(2):110-118
- CountryRepublic of Korea
- Language:English
-
Abstract:
According to the expansion of lifespan, neuronal disorder based on inflammation has been social problem. Therefore, we isolated shikonin from Lithospermum erythrorhizon and evaluated anti-inflammatory effects of shikonin in lipopolysaccharide (LSP)-stimulated BV2 microglial cells. Shikonin dose-dependently inhibits the expression of the proinflammatory mediators, nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-alpha (TNF-alpha) as well as their main regulatory genes and products such as inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-alpha in LPS-stimulated BV2 microglial cells. Additionally, shikonin suppressed the LPS-induced DNA-binding activity of nuclear factor-kappaB (NF-kappaB) to regulate the key regulatory genes of the proinflammatory mediators, such as iNOS, COX-2, and TNF-alpha, accompanied with downregulation of reactive oxygen species (ROS) generation. The results indicate that shikonin may downregulate the expression of proinflammatory genes involved in the synthesis of NO, PGE2, and TNF-alpha in LPS-treated BV2 microglial cells by suppressing ROS and NF-kappaB. Taken together, our results revealed that shikonin exerts downregulation of proinflammatory mediators by interference the ROS and NF-kappaB signaling pathway.
