Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines su...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2021-04, Vol.26 (9), p.2529
Main Authors: Kim, Haeyeop, Yang, Woo Seok, Htwe, Khin Myo, Lee, Mi-Nam, Kim, Young-Dong, Yoon, Ki Dong, Lee, Byoung-Hee, Lee, Sarah, Cho, Jae Youl
Format: Article
Language:English
Subjects:
activator protein-1 pathway
Alanine
Alanine transaminase
anti-inflammatory effects
Cytokines
D-Galactosamine
Dipterocarpus tuberculatus Roxb
Enzymes
Ethanol
Gene expression
Hepatitis
hepatitis model
Herbal medicine
IL-1β
Immune system
Inflammation
Interleukin 6
interleukin-1 receptor-associated kinase
IRAK protein
Kinases
Ligands
Lipopolysaccharides
Liver
MyD88 protein
Pathogens
Proteins
Serum levels
TAK1 protein
Transcription factors
Tumor necrosis factor-α
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Summary:Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules26092529