Table 4.

Mechanism and function of esculetin in treatment of arthritis.

Pharmacological Mechanism	Inhibition/Activation/ Downregulation/Upregulation	Model Used	Dosage	Application	Reference
Anti-arthritic	Inhibit IL-1α-induced release of proteoglycan in cartilage Downregulate proMMP-1 and MMP-3 expression in cartilage Inhibit matrix degradation in rabbit joints	OA rabbit model	10–100 µM	In vivo	[95]
	Suppress proteoglycan depletion in chondrocyte Inhibit MMP production Downregulate pro-MMP 1 and pro-MMP3 in rabbit chondrocyte	Rabbit articular chondrocyte	100 µM	In vivo	[96]
	Decrease leukotriene B4 level in plasma	AIA in male Lewis rats	10 mg/kg	In vivo	[97]
	Decline paw volume Prevent swelling, bone and cartilage destruction Downregulate Cat-D, ACP, ALP and TRAP bone degrading enzymes Inhibit endogenous generation of ROS and TNF-α, IL-1β, IL-6, COX-2 and PGE2 level Increase ALT and AST level Inhibit NF-κB and Akt signaling pathway Restore SOD, CAT and GST enzyme	AIA in adult Wistar rats	50 mg/kg	In vivo	[98]
	Inhibition of proteoglycan and collagen resorption Inhibit IL-1α + oncostatin M stimulated resorption and decreased the MMP-1 level Reduce IL-1α + oncostatin M induced expressions of MMP-1, MMP-3 and MMP-13	Transformed human chondrocyte cells (T/C28a4 cells)	66 µM, 100 µM and 50 µmol/L	In vitro	[99]