Identification and evaluation of a napyradiomycin as a potent Nrf2 activator: Anti-oxidative and anti-inflammatory activities

[Display omitted] •A series of napyradiomycins was isolated from cultured marine Streptomyces sp. YP127.•A new regioisomer of napyradiomycins (compound 1) showed ability to activate Nrf2.•Compound 1 induced expression of the Nrf2-dependent antioxidant enzyme genes.•Compound 1 attenuated H2O2-induced...

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Published in:Bioorganic chemistry 2020-12, Vol.105, p.104434-104434, Article 104434
Main Authors: Choi, Ji Won, Kim, Geum Jin, Kim, Hyeon Jeong, Nam, Joo-Won, Kim, Jushin, Chin, Jungwook, Park, Jong-Hyun, Choi, Hyukjae, Park, Ki Duk
Format: Article
Language:English
Subjects:
Anti-inflammation
Antioxidant
Napyradiomycin
Nrf2 activator
Oxidative stress
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Summary:[Display omitted] •A series of napyradiomycins was isolated from cultured marine Streptomyces sp. YP127.•A new regioisomer of napyradiomycins (compound 1) showed ability to activate Nrf2.•Compound 1 induced expression of the Nrf2-dependent antioxidant enzyme genes.•Compound 1 attenuated H2O2-induced oxidative stress in BV-2 microglial cells.•Compound 1 alleviated LPS-stimulated inflammation in BV-2 microglial cells. Natural products with antioxidant and anti-inflammatory properties are important sources of therapeutic agents. The nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is a well-known defense system against oxidative stress. In this study, a panel of extracts of plants, fungi, and bacteria were screened for Nrf2 activation in a cell-based assay and a crude extract of cultured marine Streptomyces sp. YP127 was found to activate Nrf2. Chemical investigation of the extracts led to isolation of a series of napyradiomycins that activate Nrf2. Among them, napyradiomycin, 16Z-19-hydroxynapyradiomycin A1 (1) exhibited the highest Nrf2-activating efficacy. Compound 1 was further confirmed to induce both mRNA and protein levels of Nrf2-dependent antioxidant enzyme genes in BV-2 microglial cells and suppress inflammatory mediators and intracellular reactive oxygen species. Our findings confirm the antioxidant and anti-inflammatory properties of compound 1, making it a promising therapeutic natural compound for various diseases associated with oxidative stress and inflammation.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2020.104434