Fig. 8. Schematic diagram of the synergistic mechanism of SC in reducing LPS and IFN-γ-induced proinflammatory mediators. LPS activated TLR4 receptor on the cell membrane of RAW 264.7 cells, resulting in a cascade of activation of regulators including TRAF6-pJNK-p-c-JUN signaling and NFκB translocation which induced an excessive amount of proinflammatory cytokines released from cells. In addition, the upregulated miR-155-5p expression further activated the NFκB whereas Nrf2 induced HO-1 inhibited this pathway. Our results demonstrated that combined S and C at the synergistic dosage further strengthened their inhibitory activities in NFκB translocation, and downregulated TLR4/TRAF6/MAPK pathway. However, the anti-inflammatory action of SC was likely to be independent from the induction of Nrf2.
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