2. Academic Validation
  3. A new ferroptosis inhibitor, isolated from Ajuga nipponensis, protects neuronal cells via activating NRF2-antioxidant response elements (AREs) pathway

A new ferroptosis inhibitor, isolated from Ajuga nipponensis, protects neuronal cells via activating NRF2-antioxidant response elements (AREs) pathway

  • Bioorg Chem. 2021 Oct:115:105177. doi: 10.1016/j.bioorg.2021.105177.
Qingyun Tan 1,  Yuying Fang 1,  Xing Peng 1,  Huihao Zhou 1,  Jun Xu 1,  Qiong Gu 2
Affiliations

Affiliations

  • 1 Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
  • 2 Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China. Electronic address: [email protected].
PMID: 34303035 DOI: 10.1016/j.bioorg.2021.105177
Abstract

Ferroptosis is a new form of cell death, and inhibition of Ferroptosis is a promising strategy to treat neurological diseases. In this work, sixteen compounds were isolated from Ajuga nipponensis and assayed for anti-ferroptosis activity in HT22 mouse hippocampal neuronal cells. Ajudecunoid C (1, ADC), a new neoclerodane diterpenoid, showed significant inhibitory activity against erastin and RSL3-induced Ferroptosis with EC50 values of 4.1 ± 1.0 and 3.6 ± 0.3 μM, respectively. Experimental results demonstrated that ADC effectively prevented Ferroptosis through scavenging free radical and activating NRF2-antioxidant response elements (AREs) pathway. This study reveals that ADC, as a new Ferroptosis inhibitor, is a promising lead compound for the development of drugs against ferroptosis-related neurological diseases.

Keywords

Ajuga nipponensis; Antioxidant response elements; Diterpenoid; Ferroptosis; NRF2.

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