Chrysoeriol ameliorates COX-2 expression through NF-κB, AP-1 and MAPK regulation via the TLR4/MyD88 signaling pathway in LPS-stimulated murine macrophages

Yoon,Hyun-Seo; Park,Chung Mu

doi:10.3892/etm.2021.10150

Chrysoeriol ameliorates COX-2 expression through NF-κB, AP-1 and MAPK regulation via the TLR4/MyD88 signaling pathway in LPS-stimulated murine macrophages

Authors:
- Hyun-Seo Yoon
- Chung Mu Park
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Affiliations: Department of Dental Hygiene, Dong‑Eui University, Busanjin‑gu, Busan 47340, Republic of Korea, The Research Institute for Health Functional Materials, Dong‑Eui University, Busanjin‑gu, Busan 47340, Republic of Korea
Published online on: May 3, 2021 https://doi.org/10.3892/etm.2021.10150
Article Number: 718

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Abstract

Chrysoeriol is a flavonoid that has diverse biological properties, including antioxidation, anti‑inflammation, chemoprevention and immunomodulation. Despite its reported anti‑inflammatory activity, the exact underlying molecular mechanism has not yet been elucidated. In the current study, the anti‑inflammatory mechanism of chrysoeriol involving lipopolysaccharide (LPS)‑induced cyclooxygenase‑2 (COX-2) and its upstream signaling molecules was investigated in RAW 264.7 cells. The mechanism was evaluated via ELISA and western blotting assays. Chrysoeriol significantly inhibited LPS‑induced prostaglandin E2 (PGE2) production and COX‑2 expression without cytotoxicity. Activated transcription factors that further induced the inflammation response, including nuclear factor (NF)‑κB and activator protein‑1 (AP‑1), were significantly attenuated by chrysoeriol treatment. Furthermore, LPS‑induced phosphorylation levels of phosphoinositide‑3‑kinase (PI3K)/Akt and mitogen‑activated protein kinase (MAPK) were abolished by chrysoeriol treatment, which was confirmed by selective inhibitors. Additionally, chrysoeriol significantly inhibited the LPS‑induced activation of adaptor molecules in RAW 264.7 cells, including toll‑like receptor 4 (TLR4) and myeloid differentiation primary response 88. Therefore, the results suggested that chrysoeriol ameliorates TLR4‑mediated inflammatory responses by inhibiting NF‑κB and AP‑1 activation as well as suppressing PI3K/Akt and MAPK phosphorylation in LPS‑stimulated RAW 264.7 cells.

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