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Anti-inflammatory and antioxidant mechanisms of urolithin B in activated microglia

Title
Anti-inflammatory and antioxidant mechanisms of urolithin B in activated microglia
Authors
Lee G.Park J.-S.Lee E.-J.Ahn J.-H.Kim H.-S.
Ewha Authors
김희선안정혁
SCOPUS Author ID
김희선scopus; 안정혁scopus
Issue Date
2019
Journal Title
Phytomedicine
ISSN
0944-7113JCR Link
Citation
Phytomedicine vol. 55, pp. 50 - 57
Keywords
Anti-inflammatoryAntioxidantMicrogliaMolecular mechanismsNeuroinflammationUrolithin B
Publisher
Elsevier GmbH
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
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
DOI
10.1016/j.phymed.2018.06.032
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의과대학 > 의학과 > Journal papers
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