Dysiarenone from Marine Sponge Dysidea arenaria Attenuates ROS and Inflammation via Inhibition of 5-LOX/NF-κB/MAPKs and Upregulation of Nrf-2/OH-1 in RAW 264.7 Macrophages

Tian-Yong Hu,1,* Hua Zhang,1,* Yan-Yan Chen,1 Wei-Hua Jiao,2 Jun-Ting Fan,3 Zhi-Qiang Liu,1 Hou-Wen Lin,2 Bao-Hui Cheng1 1Shenzhen Key Laboratory of ENT, Institute of ENT and Longgang ENT Hospital, Shenzhen, 518172, People’s Republic of China; 2Research Center for Marine Drugs, State Key L...

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Autores principales: Hu TY, Zhang H, Chen YY, Jiao WH, Fan JT, Liu ZQ, Lin HW, Cheng BH
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:d690c6bce8f34872a397cf720e6f08732021-12-02T11:03:09ZDysiarenone from Marine Sponge Dysidea arenaria Attenuates ROS and Inflammation via Inhibition of 5-LOX/NF-κB/MAPKs and Upregulation of Nrf-2/OH-1 in RAW 264.7 Macrophages1178-7031https://doaj.org/article/d690c6bce8f34872a397cf720e6f08732021-02-01T00:00:00Zhttps://www.dovepress.com/dysiarenone-from-marine-sponge-dysidea-arenaria-attenuates-ros-and-inf-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Tian-Yong Hu,1,* Hua Zhang,1,* Yan-Yan Chen,1 Wei-Hua Jiao,2 Jun-Ting Fan,3 Zhi-Qiang Liu,1 Hou-Wen Lin,2 Bao-Hui Cheng1 1Shenzhen Key Laboratory of ENT, Institute of ENT and Longgang ENT Hospital, Shenzhen, 518172, People’s Republic of China; 2Research Center for Marine Drugs, State Key Laboratory of Oncogene and Related Genes, Department of Pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of China; 3Department of Pharmaceutical Analysis, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hou-Wen LinShanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, People’s Republic of ChinaEmail franklin67@126.comBao-Hui ChengShenzhen Key Laboratory of ENT, Institute of ENT and Longgang ENT Hospital, 3004, Longgang Avenue, Longgang District, Shenzhen, 518172, People’s Republic of ChinaEmail chengbaohui@sina.comBackground: Marine natural products harbor a variety of pharmacological activities, and the sea species have been becoming a main source of new drug candidate. In pursuit of safer and more effective anti-inflammation drug, the anti-inflammatory activities, anti-oxygenation effects and underlying molecular mechanisms of compound dysiarenone from Dysidea arenaria were investigated via LPS-induced RAW 264.7 cell model.Methods: Firstly, RAW 264.7 cells have been stimulated with LPS and treated with dysiarenone, and the cell viability of the LPS-treated RAW 264.7 cells was examined. One-step method, DCFH-DA fluorescence probe method was used to detect reactive oxygen species (ROS). The modulation of dysiarenone on anti-inflammation was detected by enzyme-linked immunosorbent assay by measuring the release of inflammatory cytokines (TNF-α and IL-6), and inflammatory mediators (LTB4). Further, the underlying anti-inflammatory mechanism of dysiarenone was explored by determining the expression of inducible 5-LOX, MAPKs, p-Akt, and p-NF-κB p65. Oxidative stress is tightly connected with inflammation, which was also evaluated through nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (OH-1) signaling pathway.Results: Our study unraveled that dysiarenone between 2 and 8 μM reduces the inflammation responses via suppressing the production of inflammatory cytokines (TNF-α and IL-6) and inflammatory mediators (LTB4). Dysiarenone down-regulated the protein levels of inducible 5-LOX via the inhibition of phosphorylation of MAPKs (including p38, ERK), Akt and NF-κB p65. Additionally, dysiarenone decreases ROS accumulation by upregulating HO-1 expression via nuclear translocation of Nrf2.Conclusion: In conclusion, we demonstrated that dysiarenone possesses anti-inflammation and anti-oxidation activity via inhibiting 5-LOX/NF-κB/MAPK and Nrf2/HO-1 signaling pathway. Dysiarenone might be a promising lead compound for inflammatory diseases.Keywords: dysiarenone, Dysidea arenaria, Nrf2, HO-1, NF-κBHu TYZhang HChen YYJiao WHFan JTLiu ZQLin HWCheng BHDove Medical Pressarticledysiarenonedysidea arenarianrf2ho-1nf-κbPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 587-597 (2021)
institution DOAJ
collection DOAJ
language EN
topic dysiarenone
dysidea arenaria
nrf2
ho-1
nf-κb
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle dysiarenone
dysidea arenaria
nrf2
ho-1
nf-κb
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Hu TY
Zhang H
Chen YY
Jiao WH
Fan JT
Liu ZQ
Lin HW
Cheng BH
Dysiarenone from Marine Sponge Dysidea arenaria Attenuates ROS and Inflammation via Inhibition of 5-LOX/NF-κB/MAPKs and Upregulation of Nrf-2/OH-1 in RAW 264.7 Macrophages
description Tian-Yong Hu,1,* Hua Zhang,1,* Yan-Yan Chen,1 Wei-Hua Jiao,2 Jun-Ting Fan,3 Zhi-Qiang Liu,1 Hou-Wen Lin,2 Bao-Hui Cheng1 1Shenzhen Key Laboratory of ENT, Institute of ENT and Longgang ENT Hospital, Shenzhen, 518172, People’s Republic of China; 2Research Center for Marine Drugs, State Key Laboratory of Oncogene and Related Genes, Department of Pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of China; 3Department of Pharmaceutical Analysis, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hou-Wen LinShanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, People’s Republic of ChinaEmail franklin67@126.comBao-Hui ChengShenzhen Key Laboratory of ENT, Institute of ENT and Longgang ENT Hospital, 3004, Longgang Avenue, Longgang District, Shenzhen, 518172, People’s Republic of ChinaEmail chengbaohui@sina.comBackground: Marine natural products harbor a variety of pharmacological activities, and the sea species have been becoming a main source of new drug candidate. In pursuit of safer and more effective anti-inflammation drug, the anti-inflammatory activities, anti-oxygenation effects and underlying molecular mechanisms of compound dysiarenone from Dysidea arenaria were investigated via LPS-induced RAW 264.7 cell model.Methods: Firstly, RAW 264.7 cells have been stimulated with LPS and treated with dysiarenone, and the cell viability of the LPS-treated RAW 264.7 cells was examined. One-step method, DCFH-DA fluorescence probe method was used to detect reactive oxygen species (ROS). The modulation of dysiarenone on anti-inflammation was detected by enzyme-linked immunosorbent assay by measuring the release of inflammatory cytokines (TNF-α and IL-6), and inflammatory mediators (LTB4). Further, the underlying anti-inflammatory mechanism of dysiarenone was explored by determining the expression of inducible 5-LOX, MAPKs, p-Akt, and p-NF-κB p65. Oxidative stress is tightly connected with inflammation, which was also evaluated through nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (OH-1) signaling pathway.Results: Our study unraveled that dysiarenone between 2 and 8 μM reduces the inflammation responses via suppressing the production of inflammatory cytokines (TNF-α and IL-6) and inflammatory mediators (LTB4). Dysiarenone down-regulated the protein levels of inducible 5-LOX via the inhibition of phosphorylation of MAPKs (including p38, ERK), Akt and NF-κB p65. Additionally, dysiarenone decreases ROS accumulation by upregulating HO-1 expression via nuclear translocation of Nrf2.Conclusion: In conclusion, we demonstrated that dysiarenone possesses anti-inflammation and anti-oxidation activity via inhibiting 5-LOX/NF-κB/MAPK and Nrf2/HO-1 signaling pathway. Dysiarenone might be a promising lead compound for inflammatory diseases.Keywords: dysiarenone, Dysidea arenaria, Nrf2, HO-1, NF-κB
format article
author Hu TY
Zhang H
Chen YY
Jiao WH
Fan JT
Liu ZQ
Lin HW
Cheng BH
author_facet Hu TY
Zhang H
Chen YY
Jiao WH
Fan JT
Liu ZQ
Lin HW
Cheng BH
author_sort Hu TY
title Dysiarenone from Marine Sponge Dysidea arenaria Attenuates ROS and Inflammation via Inhibition of 5-LOX/NF-κB/MAPKs and Upregulation of Nrf-2/OH-1 in RAW 264.7 Macrophages
title_short Dysiarenone from Marine Sponge Dysidea arenaria Attenuates ROS and Inflammation via Inhibition of 5-LOX/NF-κB/MAPKs and Upregulation of Nrf-2/OH-1 in RAW 264.7 Macrophages
title_full Dysiarenone from Marine Sponge Dysidea arenaria Attenuates ROS and Inflammation via Inhibition of 5-LOX/NF-κB/MAPKs and Upregulation of Nrf-2/OH-1 in RAW 264.7 Macrophages
title_fullStr Dysiarenone from Marine Sponge Dysidea arenaria Attenuates ROS and Inflammation via Inhibition of 5-LOX/NF-κB/MAPKs and Upregulation of Nrf-2/OH-1 in RAW 264.7 Macrophages
title_full_unstemmed Dysiarenone from Marine Sponge Dysidea arenaria Attenuates ROS and Inflammation via Inhibition of 5-LOX/NF-κB/MAPKs and Upregulation of Nrf-2/OH-1 in RAW 264.7 Macrophages
title_sort dysiarenone from marine sponge dysidea arenaria attenuates ros and inflammation via inhibition of 5-lox/nf-κb/mapks and upregulation of nrf-2/oh-1 in raw 264.7 macrophages
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/d690c6bce8f34872a397cf720e6f0873
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