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Eur J Pharmacol. 2014 Oct 5;740:504-11. doi: 10.1016/j.ejphar.2014.06.037. Epub 2014 Jun 27.

Tetramethylpyrazine, a natural alkaloid, attenuates pro-inflammatory mediators induced by amyloid β and interferon-γ in rat brain microglia.

Author information

1
Department of Cardiovascular & Neurologic Diseases (Stroke Center), Hospital of Oriental Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
2
College of Oriental Medicine, Daegu Haany University, Daegu 706-060, Republic of Korea.
3
Department of East-West Medical Science, Kyung Hee University, Yongin-si 446-701, Republic of Korea.
4
Myunggok Eye Research Institute, Konyang University College of Medicine, Nonsan 320-711, Republic of Korea.
5
Department of East-West Medical Science, Kyung Hee University, Yongin-si 446-701, Republic of Korea. Electronic address: ehwang@khu.ac.kr.

Abstract

Neuroinflammation has been consistently reported as a pathological hallmark of Alzheimer׳s disease and other neurodegenerative diseases. Microglial cells are activated by diverse pathological stimuli and play key roles in development of neuroinflammation. Amyloid β peptide (Aβ), the major constituent of amyloid plaques in Alzheimer׳s brain, is known to activate cultured microglial cells to produce increased amounts of proinflammatory and neurotoxic factors. Tetramethylpyrazine (TMP) is the main bioactive alkaloid isolated from Ligusticum chuanxiong. TMP has multiple pharmacological activities, including anti-oxidant, anti-inflammatory, and anti-cancer effects. Neuroprotective potential of TMP has been demonstrated in animal models of neuropathologies. However, the efficacy of this compound for controlling Aβ-related neuropathology has not been explored yet. We examined the efficacy of TMP in the repression of inflammatory response in cultured microglial cells stimulated with Aβ25-35 in the presence of interferon (IFN)-γ. TMP significantly inhibited the Aβ25-35 and IFN-γ-stimulated productions of nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, monocyte chemoattractant protein-1, and intracellular reactive oxygen species from primary microglial cells. TMP also effectively reduced Aβ25-35 and IFN-γ-elicited NF-κB activation. In organotypic hippocampal slice cultures (OHSCs), TMP significantly blocked Aβ25-35-induced reactive oxygen species generation and phosphorylation of Akt. Furthermore, TMP also inhibited Aβ1-42-induced TNF-α and IL-1β production in primary microglial cells and neuronal death in OHSCs. These results suggest that TMP provide a possible therapeutic approach for alleviating the inflammatory progression of Alzheimer׳s disease.

KEYWORDS:

Amyloid β peptide; Brain inflammation; Microglia; Nitric oxide; Organotypic hippocampal slice culture; TNF-α

PMID:
24975095
DOI:
10.1016/j.ejphar.2014.06.037
[Indexed for MEDLINE]
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