Anti-inflammatory and antioxidant mechanisms of urolithin B in activated microglia
- 주제(키워드) Anti-inflammatory , Antioxidant , Microglia , Molecular mechanisms , Neuroinflammation , Urolithin B
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier GmbH
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000155890
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.phymed.2018.06.032
- PubMed https://pubmed.ncbi.nlm.nih.gov/30668443
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Background: Urolithin B is one of the gut microbial metabolites of ellagitannins and is found in diverse plant foods, including pomegranates, berries, walnuts, tropical fruits, and medicinal herbs. Although a number of biological activities of urolithin B have been reported, the anti-inflammatory and antioxidant effects of urolithin B in neuroinflammation have not been clearly demonstrated. Purpose: The present study aimed to investigate the anti-inflammatory and antioxidant effects of urolithin B in activated microglia and define its underlying molecular mechanisms. Study design: The effects of urolithin B on the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and cytokines were examined in BV2 microglial cells using enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction (RT-PCR), and Western blot analysis. Microglial activation in the lipopolysaccharide (LPS)-injected mouse brain was assessed using immunohistochemistry. The detailed molecular mechanisms underlying the anti-inflammatory and antioxidant effects of urolithin B were analyzed using an electrophoretic mobility shift assay, reporter gene assay, Western blot, and RT-PCR. Results: Urolithin B inhibited the production of NO and pro-inflammatory cytokines, while increased anti-inflammatory cytokine IL-10 in LPS-stimulated BV2 microglial cells. In addition, urolithin B inhibited NO, TNF-α and IL-6 production in lipoteichoic acid (LTA) or polyinosinic-polycytidylic acid (poly(I:C))-stimulated BV2 cells, suggesting that the anti-inflammatory effect of urolithin B is not confined to LPS stimulation. Urolithin B also showed an antioxidant effect by reducing intracellular reactive oxygen species (ROS) production and NADPH oxidase subunit expression, and by upregulating the antioxidant hemeoxygenase-1 expression via Nrf2/ARE signaling. More detailed mechanistic studies showed that urolithin B inhibited NF-κB activity by reducing the phosphorylation and degradation of IκBα. In addition, urolithin B suppressed the phosphorylation of JNK, ERK, and Akt, and enhanced the phosphorylation of AMPK, which is associated with anti-inflammatory and antioxidant processes. Finally, we demonstrated that urolithin B suppressed microglia activation in LPS-injected mouse brains. Conclusions: The strong anti-inflammatory and antioxidant effects of urolithin B may provide therapeutic potential for neuroinflammatory disorders that are associated with oxidative stress and microglial activation. © 2018 Elsevier GmbH
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