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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

Authors Hu TY, Zhang H, Chen YY, Jiao WH, Fan JT, Liu ZQ, Lin HW, Cheng BH

Received 21 November 2020

Accepted for publication 10 February 2021

Published 25 February 2021 Volume 2021:14 Pages 587—597

DOI https://doi.org/10.2147/JIR.S283745

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Ning Quan


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 work

Correspondence: Hou-Wen Lin
Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, People’s Republic of China
Email [email protected]
Bao-Hui Cheng
Shenzhen Key Laboratory of ENT, Institute of ENT and Longgang ENT Hospital, 3004, Longgang Avenue, Longgang District, Shenzhen, 518172, People’s Republic of China
Email [email protected]

Background: 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

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