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
  • 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.
Products