Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells.
Microglial cells play critical roles in the immune and inflammatory responses of the central nervous system (CNS). Under pathological conditions, the activation of microglia helps in restoring CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that observed in Alzheimer's and Parkinson's diseases. Crocin and crocetin, found in the fruits of gardenia and in the stigmas of saffron, have been considered for the treatment of various disorders in traditional oriental medicine. Crocin and crocetin have been reported to have diverse pharmacological functions, such as anti-hyperlipidemic, anti-atherosclerotic, and anti-cancer effects. Specifically, the neuroprotective potential of crocetin derivatives has previously been demonstrated. The specific aim of this study was to examine whether crocin or crocetin represses microglial activation. Crocin and crocetin were shown to be effective in the inhibition of LPS-induced nitric oxide (NO) release from cultured rat brain microglial cells. These compounds reduced the LPS-stimulated productions of tumor necrosis factor-α, interleukin-1β, and intracellular reactive oxygen species. The compounds also effectively reduced LPS-elicited NF-κB activation. In addition, crocin reduced NO release from microglia stimulated with interferon-γ and amyloid-β. In organotypic hippocampal slice cultures, both crocin and crocetin blocked the effect of LPS on hippocampal cell death. These results suggest that crocin and crocetin provide neuroprotection by reducing the production of various neurotoxic molecules from activated microglia.
Nam
Kyong Nyon
KN
Graduate School of East-West Medical Science, Kyung Hee University, Yongin-si 446-701, South Korea.
Park
Young-Min
YM
Jung
Hoon-Ji
HJ
Lee
Jung Yeon
JY
Min
Byung Duk
BD
Park
Seong-Uk
SU
Jung
Woo-Sang
WS
Cho
Ki-Ho
KH
Park
Ji-Ho
JH
Kang
Insug
I
Hong
Joung-Woo
JW
Lee
Eunjoo H
EH
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology*; D002338:Carotenoids / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); C487773:trans-sodium crocetinate; D014801:Vitamin A; D009569:Nitric Oxide; D002338:Carotenoids; D007371:Interferon-gamma; C029036:crocin