Anti-Inflammatory Activity of Kurarinone Involves Induction of HO-1 via the KEAP1/Nrf2 Pathway
Kurarinone, a flavonoid isolated from the roots of <i>Sophora flavescens</i>, was suggested to exert potent antioxidant and immunosuppressive effects. However, the underlying mechanisms remain unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that...
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doaj-db34febb01324e019da29671db5576362020-11-25T02:54:20ZengMDPI AGAntioxidants2076-39212020-09-01984284210.3390/antiox9090842Anti-Inflammatory Activity of Kurarinone Involves Induction of HO-1 via the KEAP1/Nrf2 PathwaySakiko Nishikawa0Yasumichi Inoue1Yuka Hori2Chiharu Miyajima3Daisuke Morishita4Nobumichi Ohoka5Shigeaki Hida6Toshiaki Makino7Hidetoshi Hayashi8Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDivision of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Kanagawa 210-9501, JapanDepartment of Molecular and Cellular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanKurarinone, a flavonoid isolated from the roots of <i>Sophora flavescens</i>, was suggested to exert potent antioxidant and immunosuppressive effects. However, the underlying mechanisms remain unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates the antioxidant defense system with anti-inflammatory activity. In the present study, we demonstrated that kurarinone activated Nrf2 and increased the expression of antioxidant enzymes, including heme oxygenase-1 (HO-1). Mechanistically, kurarinone downregulated the expression of kelch-like ECH-associated protein 1 (KEAP1), subsequently leading to the activation of Nrf2. Kurarinone also inhibited the expression of the inflammatory cytokine, interleukin (IL)-1β, and inducible nitric oxide synthase (iNos) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The overexpression of HO-1 suppressed the LPS-induced production of inflammatory mediators in RAW264.7 cells, and the immunosuppressive effects of kurarinone were partially inhibited by a treatment with Tin Protomorphyrin IX (TinPPIX), an inhibitor of HO-1. These results indicate that kurarinone activates the KEAP1/Nrf2 pathway to induce HO-1 expression, thereby exerting immunosuppressive effects.https://www.mdpi.com/2076-3921/9/9/842anti-inflammatoryantioxidantHO-1KEAP1kurarinoneNrf2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sakiko Nishikawa Yasumichi Inoue Yuka Hori Chiharu Miyajima Daisuke Morishita Nobumichi Ohoka Shigeaki Hida Toshiaki Makino Hidetoshi Hayashi |
spellingShingle |
Sakiko Nishikawa Yasumichi Inoue Yuka Hori Chiharu Miyajima Daisuke Morishita Nobumichi Ohoka Shigeaki Hida Toshiaki Makino Hidetoshi Hayashi Anti-Inflammatory Activity of Kurarinone Involves Induction of HO-1 via the KEAP1/Nrf2 Pathway Antioxidants anti-inflammatory antioxidant HO-1 KEAP1 kurarinone Nrf2 |
author_facet |
Sakiko Nishikawa Yasumichi Inoue Yuka Hori Chiharu Miyajima Daisuke Morishita Nobumichi Ohoka Shigeaki Hida Toshiaki Makino Hidetoshi Hayashi |
author_sort |
Sakiko Nishikawa |
title |
Anti-Inflammatory Activity of Kurarinone Involves Induction of HO-1 via the KEAP1/Nrf2 Pathway |
title_short |
Anti-Inflammatory Activity of Kurarinone Involves Induction of HO-1 via the KEAP1/Nrf2 Pathway |
title_full |
Anti-Inflammatory Activity of Kurarinone Involves Induction of HO-1 via the KEAP1/Nrf2 Pathway |
title_fullStr |
Anti-Inflammatory Activity of Kurarinone Involves Induction of HO-1 via the KEAP1/Nrf2 Pathway |
title_full_unstemmed |
Anti-Inflammatory Activity of Kurarinone Involves Induction of HO-1 via the KEAP1/Nrf2 Pathway |
title_sort |
anti-inflammatory activity of kurarinone involves induction of ho-1 via the keap1/nrf2 pathway |
publisher |
MDPI AG |
series |
Antioxidants |
issn |
2076-3921 |
publishDate |
2020-09-01 |
description |
Kurarinone, a flavonoid isolated from the roots of <i>Sophora flavescens</i>, was suggested to exert potent antioxidant and immunosuppressive effects. However, the underlying mechanisms remain unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates the antioxidant defense system with anti-inflammatory activity. In the present study, we demonstrated that kurarinone activated Nrf2 and increased the expression of antioxidant enzymes, including heme oxygenase-1 (HO-1). Mechanistically, kurarinone downregulated the expression of kelch-like ECH-associated protein 1 (KEAP1), subsequently leading to the activation of Nrf2. Kurarinone also inhibited the expression of the inflammatory cytokine, interleukin (IL)-1β, and inducible nitric oxide synthase (iNos) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The overexpression of HO-1 suppressed the LPS-induced production of inflammatory mediators in RAW264.7 cells, and the immunosuppressive effects of kurarinone were partially inhibited by a treatment with Tin Protomorphyrin IX (TinPPIX), an inhibitor of HO-1. These results indicate that kurarinone activates the KEAP1/Nrf2 pathway to induce HO-1 expression, thereby exerting immunosuppressive effects. |
topic |
anti-inflammatory antioxidant HO-1 KEAP1 kurarinone Nrf2 |
url |
https://www.mdpi.com/2076-3921/9/9/842 |
work_keys_str_mv |
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