FIGURE 2.

Effects and mechanisms of sinomenine in cerebral ischemia. Sinomenine can suppress the OGD-induced increase in SP1 and miRNA-183-5p expression in microglia, thereby causing the decrease in IκB-α expression by targeting the 3′-UTR site of mouse IκB-α, which subsequently reduces NF-κB activation and neuroinflammation Qin et al. (2018). Sinomenine may also suppress NO-mediated oxidative stress by restoring impaired Nrf2 and subsequent HO-1-NQO1 signaling in microglia Bi et al. (2021). Moreover, sinomenine can reverse OGD-induced dephosphorylation of AMPK in microglia, resulting in inhibition of the NLRP3 complex, which in turn reduces the overproduction of pro-inflammatory cytokines Qiu et al. (2016a). Sinomenine can also enhance DRD2-mediated CRYAB nuclear translocation and subsequent suppression of nuclear STAT3 and neuroinflammation in MCAO-stimulated brain tissues and OGD-stimulated astrocytes Qiu et al. (2016b). Inhibition of ASIC1a- or L-type Ca²⁺ channels-mediated Ca²⁺-CaMKII signaling is also a potential mechanism for the anti-apoptotic effect of sinomenine in neurons Wu et al. (2011), Yang et al. (2016a). However, it is currently unclear how sinomenine suppresses neuronal ASIC1a and L-type Ca²⁺ channels, suppresses microglial SP1, and increases phospho-AMPK in microglia or DRD2 function in astrocytes.