2. Academic Validation
  3. Identification and evaluation of a napyradiomycin as a potent Nrf2 activator: Anti-oxidative and anti-inflammatory activities

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

  • Bioorg Chem. 2020 Dec;105:104434. doi: 10.1016/j.bioorg.2020.104434.
Ji Won Choi 1,  Geum Jin Kim 2,  Hyeon Jeong Kim 3,  Joo-Won Nam 4,  Jushin Kim 3,  Jungwook Chin 5,  Jong-Hyun Park 1,  Hyukjae Choi 6,  Ki Duk Park 7
Affiliations

Affiliations

  • 1 Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
  • 2 College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea; Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea.
  • 3 Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
  • 4 College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea.
  • 5 New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Republic of Korea.
  • 6 College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea; Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: [email protected].
  • 7 Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea. Electronic address: [email protected].
PMID: 33161250 DOI: 10.1016/j.bioorg.2020.104434
Abstract

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.

Keywords

Anti-inflammation; Antioxidant; Napyradiomycin; Nrf2 activator; Oxidative stress.

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