FIGURE 5.

Probable mechanism of action of ISL on the Nrf2 pathway. ISL alleviated oxidative stress, cell apoptosis and inflammation via activating the AMPK/Nrf2 antioxidant signal pathway and inhibiting the NLRP3 inflammasome activation and NF-κB pathway. The inhibitory effect of ISL on NLRP3 inflammasome and NF-κB pathway may be through both Nrf2 and non-Nrf2-independent signaling events. ISL also phosphorylates MAPKs and upregulates the Keap1, which induces the separation of Nrf2 from Keap1, activation of Nrf2 signaling, and enhancement of detoxification phase II enzymes activity. ISL activates SIRT1 to promote the Nrf2 antioxidant signaling pathway. Moreover, ISL also increase its antioxidant ability and decrease in inflammatory, cell apoptosis through activating the PGC-1α/Nrf2 pathway. Besides, ISL also can inhibit GSK-3β activity by phosphorylation to enhance the Nrf2 related antioxidant gene expression and inhibit the NF-κB induced inflammatory gene. (↑) represent positive effect while (⊥) represent negative effect on the pathway.