Anti-inflammatory mechanism of compound K in activated microglia and its neuroprotective effect on experimental stroke in mice.

Abstract

Microglial activation plays a pivotal role in the pathogenesis of various neurologic disorders, such as cerebral ischemia, Alzheimer's disease, and Parkinson's disease. Thus, controlling microglial activation is a promising therapeutic strategy for such brain diseases. In the present study, we found that a ginseng saponin metabolite, compound K [20-O-D-glucopyranosyl-20(S)-protopanaxadiol], inhibited the expressions of inducible nitric-oxide synthase, proinflammatory cytokines, monocyte chemotactic protein-1, matrix metalloproteinase-3, and matrix metalloproteinase-9 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and primary cultured microglia. Subsequent mechanistic studies revealed that compound K suppressed microglial activation via inhibiting reactive oxygen species, mitogen-activated protein kinases, and nuclear factor-κB/activator protein-1 activities with enhancement of heme oxygenase-1/antioxidant response element signaling. To address the anti-inflammatory effects of compound K in vivo, we used two brain disease models of mice: sepsis (systemic inflammation) and cerebral ischemia. Compound K reduced the number of Iba1-positive activated microglia and inhibited the expressions of tumor necrosis factor-α and interleukin-1β in the LPS-induced sepsis brain. Furthermore, compound K reduced the infarct volume of ischemic brain induced by middle cerebral artery occlusion and suppressed microglial activation in the ischemic cortex. The results collectively suggest that compound K is a promising agent for prevention and/or treatment of cerebral ischemia and other neuroinflammatory disorders.

• Authors: Jin-Sun Park, Jin A Shin, Ji-Sun Jung, Jin-Won Hyun, Thi Kim Van Le, Dong-Hyun Kim, Eun-Mi Park, Hee-Sun Kim
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 341 Issue 1 Pg. 59-67 (Apr 2012) ISSN: 1521-0103 [Electronic] United States
• PMID: 22207656 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Ginsenosides
• Neuroprotective Agents
• ginsenoside M1

Topics

• Animals
• Animals, Newborn
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Cells, Cultured
• Ginsenosides (pharmacology, therapeutic use)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Microglia (drug effects, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Panax
• Rats
• Rats, Sprague-Dawley
• Stroke (metabolism, prevention & control)