The role of resveratrol on rheumatoid arthritis: From bench to bedside

FIGURE 1. The RA molecular regulation chain surrounding SIRT1. SIRT1 can downregulate NF-κB and MMP1/MMP13, both of which promote the invasion of RA. NF-κB participates in mir-29a-3p/Keap1 and mir-23a-3p/Cul3. They both regulate downstream Nrf2, mediate ARE expression, and produce ROS. On the other hand, BK/B2R/PKCμ Pathway and Nrf2/ARE/ROS pathway can act on downstream MAPK, which can mediate AP-1 and NF-κB, thus forming a closed loop of complex signaling pathways starting from the SIRT1 pathway.

FIGURE 2. Resveratrol inhibits RA by promoting apoptosis. Resveratrol inhibits the expression of BCL-XL in MH7A cells, which enhances the activation of caspase-8 in fls-85 cells and causes the efficient release of cytoc in mitochondria, eventually activating caspase-9 and caspase-3, and promoting apoptosis.

FIGURE 3. Resveratrol is closely related to innate immunity and autoimmunity, which can reduce the number of immune cells and inhibit the function of immune cells through intact mechanisms. Resveratrol can inhibit the PMA-induced phosphorylation and nuclear translocation of PU.1, thus inhibiting monocyte differentiation into macrophages. Resveratrol can also inhibit the function of Th1 and Th17 cells.

FIGURE 4. A drug delivery system idea for resveratrol. QRU-PLGA-RES-DS nanoparticles can effectively aggregate at the lesion site, promote the transformation of M2 macrophages, and reduce the recruitment of M1 macrophages, so as to effectively treat RA by eliminating an inflammatory response.