title: Tetramethylpyrazine, a natural alkaloid, attenuates pro-inflammatory mediators induced by amyloid β and interferon-γ in rat brain microglia.
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.
authors: Department of Cardiovascular & Neurologic Diseases (Stroke Center), Hospital of Oriental Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors: Mia
authors: M
authors: Kim
authors: College of Oriental Medicine, Daegu Haany University, Daegu 706-060, Republic of Korea.
authors: Sung-Ok
authors: SO
authors: Kim
authors: Department of East-West Medical Science, Kyung Hee University, Yongin-si 446-701, Republic of Korea.
authors: Moonsung
authors: M
authors: Lee
authors: Myunggok Eye Research Institute, Konyang University College of Medicine, Nonsan 320-711, Republic of Korea.
authors: Joon H
authors: JH
authors: Lee
authors: Department of Cardiovascular & Neurologic Diseases (Stroke Center), Hospital of Oriental Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors: Woo-Sang
authors: WS
authors: Jung
authors: Department of Cardiovascular & Neurologic Diseases (Stroke Center), Hospital of Oriental Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors: Sang-Kwan
authors: SK
authors: Moon
authors: Department of Cardiovascular & Neurologic Diseases (Stroke Center), Hospital of Oriental Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors: Young-Suk
authors: YS
authors: Kim
authors: Department of Cardiovascular & Neurologic Diseases (Stroke Center), Hospital of Oriental Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors: Ki-Ho
authors: KH
authors: Cho
authors: Department of Cardiovascular & Neurologic Diseases (Stroke Center), Hospital of Oriental Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors: Chang-Nam
authors: CN
authors: Ko
authors: Department of East-West Medical Science, Kyung Hee University, Yongin-si 446-701, Republic of Korea. Electronic address: ehwang@khu.ac.kr.
authors: Eunjoo H
authors: EH
authors: Lee
mesh_terms: D016229:Amyloid beta-Peptides; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments; D011719:Pyrazines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D016328:NF-kappa B; D010446:Peptide Fragments; D011719:Pyrazines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D009569:Nitric Oxide; D007371:Interferon-gamma; C017953:tetramethylpyrazine
keywords: Amyloid β peptide; Brain inflammation; Microglia; Nitric oxide; Organotypic hippocampal slice culture; TNF-α