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

<i>Dipterocarpus tuberculatus</i> 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 <i>Dipterocarpus tuberculatus</i> Roxb. ethanol extract (Dt-EE)....

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Main Authors: Haeyeop Kim, Woo Seok Yang, Khin Myo Htwe, Mi-Nam Lee, Young-Dong Kim, Ki Dong Yoon, Byoung-Hee Lee, Sarah Lee, Jae Youl Cho
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/9/2529
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author Haeyeop Kim
Woo Seok Yang
Khin Myo Htwe
Mi-Nam Lee
Young-Dong Kim
Ki Dong Yoon
Byoung-Hee Lee
Sarah Lee
Jae Youl Cho
author_facet Haeyeop Kim
Woo Seok Yang
Khin Myo Htwe
Mi-Nam Lee
Young-Dong Kim
Ki Dong Yoon
Byoung-Hee Lee
Sarah Lee
Jae Youl Cho
author_sort Haeyeop Kim
collection DOAJ
description <i>Dipterocarpus tuberculatus</i> 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 <i>Dipterocarpus tuberculatus</i> 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.
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spelling doaj.art-bdc2432c55c146c39eff86d99bd996562023-11-21T17:16:28ZengMDPI AGMolecules1420-30492021-04-01269252910.3390/molecules26092529<i>Dipterocarpus tuberculatus</i> Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 PathwayHaeyeop Kim0Woo Seok Yang1Khin Myo Htwe2Mi-Nam Lee3Young-Dong Kim4Ki Dong Yoon5Byoung-Hee Lee6Sarah Lee7Jae Youl Cho8Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, KoreaDepartment of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, KoreaPopa Mountain Park, Forest Department, Kyaukpadaung Township, Mandalay Division, Kyaukpadaung 05241, MyanmarDepartment of Hospitality and Culinary, Ansan University, Ansan 15318, KoreaDepartment of Life Science, Hallym University, Chuncheon 200-702, KoreaCollege of Pharmacy, The Catholic University of Korea, Bucheon 420-743, KoreaNational Institute of Biological Resources, Environmental Research Complex, Incheon 22689, KoreaNational Institute of Biological Resources, Environmental Research Complex, Incheon 22689, KoreaDepartment of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea<i>Dipterocarpus tuberculatus</i> 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 <i>Dipterocarpus tuberculatus</i> 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.https://www.mdpi.com/1420-3049/26/9/2529<i>Dipterocarpus tuberculatus</i> Roxb.anti-inflammatory effectstumor necrosis factor-αinterleukin-1 receptor-associated kinaseactivator protein-1 pathwayhepatitis model
spellingShingle Haeyeop Kim
Woo Seok Yang
Khin Myo Htwe
Mi-Nam Lee
Young-Dong Kim
Ki Dong Yoon
Byoung-Hee Lee
Sarah Lee
Jae Youl Cho
<i>Dipterocarpus tuberculatus</i> Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway
Molecules
<i>Dipterocarpus tuberculatus</i> Roxb.
anti-inflammatory effects
tumor necrosis factor-α
interleukin-1 receptor-associated kinase
activator protein-1 pathway
hepatitis model
title <i>Dipterocarpus tuberculatus</i> Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway
title_full <i>Dipterocarpus tuberculatus</i> Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway
title_fullStr <i>Dipterocarpus tuberculatus</i> Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway
title_full_unstemmed <i>Dipterocarpus tuberculatus</i> Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway
title_short <i>Dipterocarpus tuberculatus</i> Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway
title_sort i dipterocarpus tuberculatus i roxb ethanol extract has anti inflammatory and hepatoprotective effects in vitro and in vivo by targeting the irak1 ap 1 pathway
topic <i>Dipterocarpus tuberculatus</i> Roxb.
anti-inflammatory effects
tumor necrosis factor-α
interleukin-1 receptor-associated kinase
activator protein-1 pathway
hepatitis model
url https://www.mdpi.com/1420-3049/26/9/2529
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