Figure 2.

A timeline of significant discoveries in itaconate. Itaconate was first found to be a citrate distillation product through chemical methods in 1836 [12]. Itaconate was demonstrated to be as an SDH inhibitor in 1949 [105] and posess antimicrobial properties by inhibiting isocitrate lyase in 1971 [40]. Then in 2011 [46], itaconate was subsequently discovered in some inflammatory models, and the enzyme IRG1 was finally confirmed to produce itaconate in 2013 [43]. Its antioxidant and anti-inflammatory effects through activation of NRF2 were demonstrated in 2018 [15]. Its anti-inflammatory effects by activating ATF3 were also confirmed in 2018 [8]. Subsequently, itaconate induced autophagy [47], inhibited NLRP3 inflammasome activation-mediated pyroptosis [48], inhibited ferroptosis of macrophage via NRF2 pathways [49] and mediated epigenetic modifications by inhibiting TET2 [9]. Additionally, itaconate promoting macrophages M2 polarization was also confirmed in 2022 [50].