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Anti-inflammatory and antioxidant mechanisms of coniferaldehyde in lipopolysaccharide-induced neuroinflammation: Involvement of AMPK/Nrf2 and TAK1/MAPK/NF-κB signaling pathways.
Park, Jae-Min; Park, Jung-Eun; Park, Jin-Sun; Leem, Yea-Hyun; Kim, Do-Yeon; Hyun, Jin-Won; Kim, Hee-Sun.
Afiliación
  • Park JM; Department of Molecular Medicine, Inflammation-Cancer Microenvironment Research Center, School of Medicine, Ewha Womans University, Seoul, South Korea.
  • Park JE; Department of Molecular Medicine, Inflammation-Cancer Microenvironment Research Center, School of Medicine, Ewha Womans University, Seoul, South Korea.
  • Park JS; Department of Molecular Medicine, Inflammation-Cancer Microenvironment Research Center, School of Medicine, Ewha Womans University, Seoul, South Korea.
  • Leem YH; Department of Molecular Medicine, Inflammation-Cancer Microenvironment Research Center, School of Medicine, Ewha Womans University, Seoul, South Korea.
  • Kim DY; Department of Molecular Medicine, Inflammation-Cancer Microenvironment Research Center, School of Medicine, Ewha Womans University, Seoul, South Korea.
  • Hyun JW; Department of Biochemistry, College of Medicine, and Jeju Research Center for Natural Medicine, Jeju National University, Jeju, South Korea.
  • Kim HS; Department of Molecular Medicine, Inflammation-Cancer Microenvironment Research Center, School of Medicine, Ewha Womans University, Seoul, South Korea. Electronic address: hskimp@ewha.ac.kr.
Eur J Pharmacol ; 979: 176850, 2024 Sep 15.
Article en En | MEDLINE | ID: mdl-39059571
ABSTRACT
Microglia are primarily involved in inflammatory reactions and oxidative stress in the brain; as such reducing microglial activation has been proposed as a potential therapeutic strategy for neurodegenerative disorders. Herein, we investigated the anti-inflammatory and antioxidant activities of coniferaldehyde (CFA), a naturally occurring cinnamaldehyde derivative, on activated microglia to evaluate its therapeutic potential. CFA inhibited the production of nitric oxide (NO) and proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. CFA also inhibited intracellular reactive oxygen species levels and oxidative stress markers such as 4-HNE and 8-OHdG. Detailed mechanistic studies showed that CFA exerted anti-inflammatory effects by inhibiting TAK1-mediated MAP kinase/NF-κB activation and upregulating AMPK signaling pathways. In addition, CFA exerted antioxidant effects by inhibiting the NADPH oxidase subunits and by increasing the expression of antioxidant enzymes such as HO-1, NQO1, and catalase by upregulating Nrf2 signaling. Finally, we confirmed the effects of CFA on the brains of the LPS-injected mice. CFA inhibited microglial activation and the expression of proinflammatory markers and increased Nrf2-driven antioxidant enzymes. Furthermore, CFA inhibited the production of 4-HNE and 8-OHdG in the brains of LPS-injected mice. As a result, CFA's significant anti-inflammatory and antioxidant properties may have therapeutic applications in neuroinflammatory disorders related with oxidative stress and microglial activation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Lipopolisacáridos / FN-kappa B / Microglía / Quinasas Quinasa Quinasa PAM / Factor 2 Relacionado con NF-E2 / Proteínas Quinasas Activadas por AMP / Antiinflamatorios / Antioxidantes Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Lipopolisacáridos / FN-kappa B / Microglía / Quinasas Quinasa Quinasa PAM / Factor 2 Relacionado con NF-E2 / Proteínas Quinasas Activadas por AMP / Antiinflamatorios / Antioxidantes Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Países Bajos