Table 1.

The regulatory mechanism of emodin in inflammatory cytokines in RA.

Species	Inflammatory cytokines	Target	Regulation results	Refs.
Proinflammatory cytokines	TNF-α	NF-κB	TNFa, IL-6, IL-1β, IL-6, IL-33, MMP-10, and IL-8 decreased expression	[97–100]
	IL-6	PI3K/AKT	TNF-α, IL-6, PGE (2), and COX-2 decreased expression	[101, 102]
	IL-1, IL-1β	FPGE2, C'ase	PGE2, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 decreased expression	[98, 103–105]
	IL-17	G-CSF, CXC chemokine ligands 1 and 2	Balance the ratio of TH1/TH2 cells and TH17/Tregs	[69, 106, 107]
	IL-9	M-CSF/sRANKL	Inhibiting the phosphorylation of IKK and RANKL expression	[108–110]
	M-CSF	JAK2/STAT5	Enhances RANKL-dependent apoptosis of osteoclasts	[92, 111–120]
Anti-inflammatory cytokines	IL-4	MMP-13, metalloproteinase 3, and protein-like metalloproteinase 4	Inhibiting the NF-κB/IRF5/STAT1 and IRF4/STAT6 signaling pathways, Inhibiting M1-to-M2 polarization of macrophages	[75, 121–123]
	IL-10	JAK1/STAT3	Inhibiting the PI3K/AKT signaling pathways, inducing DC maturation, and promoting Th1 cell polarization	[124]
	IL-13	STAT6	IL-1β, TNF-α, IL-6, macrophage inflammatory protein 1α, macrophage inflammatory protein 1β, and macrophage inflammatory protein 3 decreased expression	[125–127]
	TGF-β	T cells, B cells, and thymocytes	Inhibiting the proliferation and differentiation of T cells, B cells, and thymocytes, limit the production of IL-2, IFN-γ, and TNF, and increase the secretion of GM-CSF	[42, 128–130]