Chunghyuldan attenuates brain microglial inflammatory response.

Abstract

Microglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory molecules and neurotoxins. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target stroke and neurodegenerative diseases. Chunghyuldan, a combinatorial drug consisting of Scutellariae Radix, Coptidis Rhizoma, Phellodendri Cortex, Gardeniae Fructus, and Rhei Rhizoma, has an inhibitory effect on stroke recurrence in patients with small-vessel disease. It has also been reported to confer antihypertensive, antihyperlipidemic, and antiinflammatory effects. The aim of this study was to examine whether Chunghyuldan suppresses microglial activation. Chunghyuldan was effective at inhibiting LPS-induced nitric oxide (NO) release from rat brain microglia. Real-time reverse transcriptase PCR analysis revealed that pretreatment of rat brain microglia with Chunghyuldan attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-alpha, interleukin-1beta, and cyclooxygenase-2. In rat brain microglia, Chunghyuldan reduced the LPS-stimulated production of TNF-alpha and prostaglandin E2. In addition, Chunghyuldan significantly decreased LPS-induced phosphorylation of the ERK1/2 and p38 signaling proteins. These results suggest that Chunghyuldan provide neuroprotection by reducing the release of various proinflammatory molecules from activated microglia.

• Authors: Kyong Nyon Nam, Hoon-Ji Jung, Mi-Hyun Kim, Chulhun Kang, Woo-Sang Jung, Ki-Ho Cho, Eunjoo H Lee
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 87 Issue 6 Pg. 448-54 (Jun 2009) ISSN: 1205-7541 [Electronic] Canada
• PMID: 19526039 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chunghyuldan
• Drugs, Chinese Herbal
• Inflammation Mediators
• Interleukin-1beta
• Lipopolysaccharides
• Neuroprotective Agents
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Cyclooxygenase 2
• Ptgs2 protein, rat

Topics

• Animals
• Animals, Newborn
• Blotting, Western
• Cell Survival (drug effects)
• Cells, Cultured
• Cyclooxygenase 2 (biosynthesis)
• Down-Regulation
• Drugs, Chinese Herbal (pharmacology)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Interleukin-1beta (biosynthesis)
• Lipopolysaccharides (pharmacology)
• Microglia (drug effects, enzymology, immunology, metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Nitric Oxide (antagonists & inhibitors, biosynthesis)
• Nitric Oxide Synthase Type II (biosynthesis)
• Rats
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (biosynthesis)