Mechanisms of flavonoid compounds exerting protective effects against brain injury after ICH. (A) Puerarin activates the PI3K/Akt pathway and reduces NF-κB activation, increases the expression level of Bcl-2 and inhibits the expression of Bax and Caspase-3, thereby inhibiting ICH-induced apoptosis. (B) Calycosin, luteolin and isoliquiritigenin protects ICH by modulating Nrf2. They both activate Nrf2 and promote its nuclear translocation, thereby inhibiting OS. In addition, calycosin and isoliquiritigenin further inhibit NF-κB and/or NLRP3-mediated inflammation through promoting Nrf2. (C) Luteolin inhibits the activation of the TLR4/TRAF6/NF-κB signaling pathway by binding to TRAF6, thus reducing inflammation. (D) Quercetin, baicalein and procyanidins increase the activities of SOD and GSH-Px, while decreasing the MDA level, and thus improves oxidative damage after ICH. (E) Baicalein and isoliquiritigenin inhibit NLRP3-mediated inflammation by inhibiting ROS production. (F) Didymin upregulates the expression of RKIP; RKIP combines with Asc, thus inhibiting the assembly of NLRP3 inflammasomes, to inhibit NLRP3-mediated inflammatory response. (G) Quercetin inhibits apoptosis mediated by cleaved Caspase-3. (H) Baicalin downregulates the expression of PAR-1 to inhibit cellular apoptosis. (I) Baicalin inhibits the expression of MMPs to ameliorate the disruption of BBB. (J) Breviscapine attenuates the inflammatory response by inhibiting the activation of NF-κB. (K) Eupatilin and pinocembrin lower the expression of TLR4 and downregulate NF-κB signaling to inhibit the inflammatory response. (L) Hesperidin promotes the expression of TGF-β1 to inhibit expression of MMPs, thus protecting the BBB from disruption. ICH, intracerebral hemorrhage; OS, oxidative stress; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; MDA, malondialdehyde; ROS, reactive oxygen species; RKIP, RAF kinase inhibitor protein; PAR-1, protease-activating receptor-1; MMP, matrix metalloproteinases; BBB, blood-brain barrier
