Identification and evaluation of a napyradiomycin as a potent Nrf2 activator: antioxidative and anti-inflammatory activities
- Identification and evaluation of a napyradiomycin as a potent Nrf2 activator: antioxidative and anti-inflammatory activities
- 박기덕; 박종현; 최지원; 김현정; 김주신; 김금진; 남주원; 진정욱; 최혁재
- Issue Date
- Bioorganic chemistry
- VOL 105, 104434
- 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.
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