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  3. A novel chalcone derivative as Nrf2 activator attenuates learning and memory impairment in a scopolamine-induced mouse model

A novel chalcone derivative as Nrf2 activator attenuates learning and memory impairment in a scopolamine-induced mouse model

  • Eur J Med Chem. 2020 Jan 1;185:111777. doi: 10.1016/j.ejmech.2019.111777.
Hyeon Jeong Kim 1,  Bo Ko Jang 2,  Jong-Hyun Park 2,  Ji Won Choi 2,  Sun Jun Park 3,  Seong Rim Byeon 4,  Ae Nim Pae 5,  Yong Sup Lee 6,  Eunji Cheong 7,  Ki Duk Park 8
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; Department of Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
  • 2 Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul, 02792, 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; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea.
  • 4 Kainos Medicine, Inc., Daewangpangyo-ro, Seongnam, Gyeonggi, 13488, Republic of Korea.
  • 5 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; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, 02447, Republic of Korea.
  • 6 KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, 02447, Republic of Korea; Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea.
  • 7 Department of Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
  • 8 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; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address: kdpark@kist.re.kr.
PMID: 31670201 DOI: 10.1016/j.ejmech.2019.111777
Abstract

Alzheimer's disease is a common neurodegenerative disease characterized by progressive degeneration and neuronal cell death, resulting in neural network dysfunction. As the underlying mechanisms, oxidative damage and neuroinflammation have been reported to contribute to the onset and deterioration of Alzheimer's disease. The nuclear factor E2-related factor 2-antioxidant responsive element signaling pathway is a pivotal cellular defense mechanism against oxidative stress. Nrf2, a transcription factor, regulates the cellular redox balance and is primarily involved in anti-inflammatory responses. In this study, we synthesized novel chalcone derivatives and found a highly potent Nrf2 activator, compound 20a. Compound 20a confirmed to activate Nrf2 and induce expression of the Nrf2-dependent Enzymes HO-1 and GCLC at both mRNA and protein levels. It also suppressed the production of nitric oxide and downregulated inflammatory mediators in BV-2 microglial cells. We found that compound 20a effectively increased the expression level and the activity of superoxide dismutase in both BV-2 microglial cells and brain hippocampus region of the scopolamine-induced mouse model. In addition, compound 20a effectively recovered the learning and memory impairment in a scopolamine-induced mouse model.

Keywords

Alzheimer’s disease; Chalcone; Nuclear factor erythroid 2-related factor 2; Oxidative stress; Superoxide dismutase.

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