期刊
NEUROCHEMISTRY INTERNATIONAL
卷 171, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2023.105613
关键词
Nobiletin; Neuroinflammation; JNK; Microglia; NF-kappa B
Nobiletin, a flavonoid found in shikuwasa, has been shown to have anti-inflammatory effects by inhibiting the production of inflammatory substances and reducing neuroinflammation in mice. These findings suggest that nobiletin could be a potential drug for preventing neuroinflammation.
Nobiletin (5,6,7,8,3 ',4 '-hexamethoxyflavone) is one of the flavonoids found in shikuwasa, a popular citrus fruit in Okinawa, Japan. It exerts various pharmacological effects, such as anti-tumor, antioxidant, and anti-inflammatory activities. We herein investigated whether nobiletin attenuated lipopolysaccharide (LPS)-induced inflammatory responses in the murine microglial cell line BV-2 and neuroinflammation in mice induced by an intracerebral injection of LPS. In BV-2 cells, nobiletin significantly inhibited the LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) by preventing the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. Nobiletin also inhibited the LPS-induced mRNA expression of CCL2, CXCL1, IL-6, and TNF alpha. Nobiletin markedly attenuated the transcriptional activity of the NF-kappa B p65 subunit without affecting the degradation of I kappa B alpha or the nuclear localization of the NF-kappa B p65 subunit. Nobiletin also inhibited the LPS-induced activation of JNK, but not ERK or p38, in BV-2 cells. Furthermore, the administration of nobiletin significantly suppressed the accumulation of microglia and induction of the mRNA expression of CCL2, CXCL1, IL-6, and TNF alpha in the murine brain induced by injecting LPS into the striatum. Collectively, these results suggest the potential of nobiletin as a candidate anti-inflammatory drug for the prevention of neuroinflammation.
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