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Anti-inflammatory and Antioxidant Mechanisms of Urolithin B in Activated Microglia

Anti-inflammatory and Antioxidant Mechanisms of Urolithin B in Activated Microglia

Gyeongjin Lee, Jin-Sun Park, Eun-Jung Lee, Jung-Hyuck Ahn, Hee-Sun Kim

Phytomedicine. 2019 Mar 1;55:50-57.

PMID: 30668443

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1139839	Urolithin B		1139-83-9	Price

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