Biomol Ther.  2015 Mar;23(2):110-118. 10.4062/biomolther.2015.006.

Shikonin Isolated from Lithospermum erythrorhizon Downregulates Proinflammatory Mediators in Lipopolysaccharide-Stimulated BV2 Microglial Cells by Suppressing Crosstalk between Reactive Oxygen Species and NF-kappaB

Affiliations
  • 1Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea. immunkim@jejunu.ac.kr
  • 2Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-051, Republic of Korea.

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.

Keyword

Shikonin; Proinflammatory mediators; Reactive oxygen species; Nuclear factor-kappaB

MeSH Terms

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
Cyclooxygenase 2
Dinoprostone
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase
Reactive Oxygen Species
Tumor Necrosis Factor-alpha
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