Table 1.

The anti-RA activities of sinomenine derivatives.

Compound	Cell Model and Efficacy	Animal Model	Potential Targets or Pathways	Cytotoxicity or Side Effects	Ref.
2	rat splenocytes	croton oil-induced ear edema	IL-2	— 1	[56]
3	LPS-induced RAW264.7 cells	dimethylbenzene-induced ear edema, carrageenan-induced paw edema	IL-1β, TNF-α	—	[57]
4, 5	LPS-induced RAW264.7 cells	dimethylbenzene-induced ear edema, carrageenan-induced paw edema	IL-1β, TNF-α	no obvious cytotoxicity in peritoneal macrophages at concentrations below 0.02 mg/mL	[58]
6	TNF-α-induced mouse embryonic fibroblasts	carrageenan-induced paw edema	NF-κB	cytotoxicity in mouse embryonic fibroblasts, IC50 = 38.9 μM	[59]
7	—	chronic constriction injury model, complete Freund’s adjuvant-induced mechanical allodynia	GABAA receptor	no sedation or allergic reactions at a dose of 80 mg/kg	[60]
8	LPS-induced RAW264.7 cells, NO production inhibition, IC50 = 15.2 μM (sinomenine concentration >200 μM); fibroblast-like synovial cells (FLSCs)	LPS-induced septic shock model, collagen-induced arthritis	TNF-α, IL-6, NF-κB, IκBα; not the MAPK pathway	cytotoxicity in RAW264.7 cells, IC50 = 41.1 μM (sinomenine, IC50 >200 μM); no inhibition of FLSC growth at 30 μM	[61,62]
9	Bone-marrow-derived dendritic cells	EAE model	TNF-α, IL-6		[63]
10, 11	LPS-induced peritoneal macrophages, 99% inhibition of TNF-α activity at 10 μM (sinomenine, 11% inhibitory rate)	—	TNF-α	—	[64]
12	LPS-induced ANA-1/peritoneal macrophages	LPS-induced endotoxemia model	P38/AKT or STAT1 pathways	—	[65]
13	LPS-induced RAW264.7 cells, NO production inhibition, IC50 = 30.28 ± 1.70 μM (sinomenine, IC50 = 70.86 ± 1.00 μM)	carrageenan-induced paw edema, acetic-acid-induced writhing test	NF-κB, iNOS	no obvious cytotoxicity in RAW264.7 cells	[66]
14	—	carrageenan-induced paw edema, AIA model	—	no hemolytic activity	[67]

¹ Not mentioned in the literature.