Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김희선 | * |
dc.contributor.author | 박진선 | * |
dc.contributor.author | 임예현 | * |
dc.date.accessioned | 2021-02-25T16:31:46Z | - |
dc.date.available | 2021-02-25T16:31:46Z | - |
dc.date.issued | 2021 | * |
dc.identifier.issn | 0891-5849 | * |
dc.identifier.issn | 1873-4596 | * |
dc.identifier.other | OAK-28901 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/257144 | - |
dc.description.abstract | Neuroinflammation and oxidative stress play key roles in the progression of neurodegenerative diseases. Thus, the use of potent anti-inflammatory/antioxidant agents has been suggested as a promising therapeutic strategy for neurodegenerative diseases. In the present study, we investigated the anti-inflammatory and antioxidant effects of nootkatone (NKT), a sesquiterpenoid compound isolated from grapefruit, in in vitro and in vivo models of neuroinflammation. In lipopolysaccharide (LPS)-stimulated BV2 microglial cells, NKT inhibited the expression of iNOS, COX-2, and pro-inflammatory cytokines, and increased the expression of the anti-inflammatory cytokine, IL-10. In addition, NKT inhibited reactive oxygen species (ROS) production and upregulated the expression of antioxidant enzymes, such as NQO1 and HO-1. Molecular mechanistic studies showed that NKT inhibited Akt, p38 MAPK, and NF-kappa B activities, while increasing AMPK, PKA/CREB, and Nrf2/ARE signaling in LPS-stimulated BV2 cells. Since NKT dramatically increased NQO1 expression, we investigated the role of this enzyme using pharmacological inhibition or knockdown experiments. Treatment of BV2 cells with the NQO1-specific inhibitor, dicoumarol, or with NQO1 siRNA significantly blocked NKT-mediated inhibition of NO, ROS, TNF-alpha, IL-1 beta, and upregulation of IL-10. Furthermore, NQO1 inhibition reversed the effects of NKT on pm- and anti-inflammatory signaling molecules. Intriguingly, we found that the AMPK inhibitor, compound C, mimicked the effects of dicoumarol, suggesting the presence of a crosstalk between NQO1 and AMPK. Finally, we demonstrated that NKT inhibited microglial activation, lipid peroxidation, and the expression of pro-inflammatory markers in the brains of LPS-injected mice, which was also reversed by dicoumarol. These data collectively suggest that NQO1 plays a critical role in mediating the anti-inflammatory and antioxidant effects of NKT in LPS-induced neuroinflammation by modulating AMPK and its downstream signaling pathways. | * |
dc.language | English | * |
dc.publisher | ELSEVIER SCIENCE INC | * |
dc.subject | Microglia | * |
dc.subject | Nootkatone | * |
dc.subject | Anti-inflammatory | * |
dc.subject | Antioxidant | * |
dc.subject | NQO1 | * |
dc.subject | AMPK signaling | * |
dc.title | NQO1 mediates the anti-inflammatory effects of nootkatone in lipopolysaccharide-induced neuroinflammation by modulating the AMPK signaling pathway | * |
dc.type | Article | * |
dc.relation.volume | 164 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 354 | * |
dc.relation.lastpage | 368 | * |
dc.relation.journaltitle | FREE RADICAL BIOLOGY AND MEDICINE | * |
dc.identifier.doi | 10.1016/j.freeradbiomed.2021.01.015 | * |
dc.identifier.wosid | WOS:000621320000003 | * |
dc.identifier.scopusid | 2-s2.0-85100217770 | * |
dc.author.google | Park, Jung-Eun | * |
dc.author.google | Park, Jin-Sun | * |
dc.author.google | Leem, Yea-Hyun | * |
dc.author.google | Kim, Do-Yeon | * |
dc.author.google | Kim, Hee-Sun | * |
dc.contributor.scopusid | 김희선(57191372551) | * |
dc.contributor.scopusid | 박진선(54914743600) | * |
dc.contributor.scopusid | 임예현(25422269100) | * |
dc.date.modifydate | 20240222143226 | * |