Figure 5.

Mechanism of Kunxian capsule in treating RA. The red nodes represent targets in Kunxian capsule. (A) Through intermediate protein Gβγ, GPCRs regulated the activation of PI3Ks. The phosphorylation of PI3K activated AKT which lead to downstream cascades, such as controlling cell proliferation, protein translation. JAK-STAT signaling is related with the proliferation of the inflammatory cells. Lastly, cAMP, a second messenger affected by calcium signaling pathway, could activate PI3K via intermediate molecules, such as PKA and mTOR, which are high degree targets in KX. KX inhibits the three pathways and decrease cell proliferation and promote cell apoptosis in RA. (B) Th17 cells could be activated by IL-1β (through mTOR-ROR) or IL-6 (through STAT3-HIF1-ROR). Subsequently, the activated TH17 cells released IL-17, which activated the downstream effector cells, such as monocytes, macrophages, and synovial fibroblast. These cells could release inflammatory cytokines which could promoted cartilage damage. KX could target at the critical checkpoints in the pathways, downregulating the inflammatory cells proliferation and alleviating cartilage damage.