A comparison study between dimethyl itaconate and dimethyl fumarate in electrophilicity, Nrf2 activation, and anti-inflammation in vitro

Abstract

Dimethyl itaconate (DMI) is an analog of dimethyl fumarate (DMF), an approved NF-E2-related Factor 2 (Nrf2) activator for multiple sclerosis. This study evaluated the potential of DMI as an anti-inflammatory agent by comparing DMI with DMF in electrophilicity, Nrf2 activation, and anti-inflammation in vitro. The results showed that DMI was less electrophilic but better at inducing a durable activation of Nrf2 when compared with DMF. However, DMI demonstrated poor anti-inflammatory effects in Jurkat cells, bone marrow-derived dendritic cells, and RAW264.7 cells. Our study suggested that DMI was a potent electrophilic Nrf2 activator but was probably not a promising anti-inflammatory agent.

Keywords:

• Dimethyl fumarate
• dimethyl itaconate
• NF-E2-related factor 2
• inflammation
• oxidative stress

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This project was financially supported by the grants from National Natural Sciences Foundation of China (No. 81872855), CAMS Innovation Fund for Medical Sciences (No.2017-I2M-2-004), and National Key R&D Program of China (No.2019YFC1708901).