Prophylactic and therapeutic roles of oleanolic acid and its derivatives in several diseases

Table 6  In vivo anti-osteoporotic and related mechanisms of action of oleanolic acid and its natural and synthetic derivatives (2014-2020)

Disease model/ physiology	Effect	Mechanism		Compound	Dose	Ref.
		↑↑↑	↓↓↓
OVX-mice	Increased bone mineral density	1,25(OH)2D3, renal CYP27B1	Urinary Ca excretion, CYP24A1	OA	50 or 100 mg/kg·d, 6 wk	[107]
OVX-mice	Better bone density	1,25(OH)2D3	Decreased urinary excreation of Ca	OA	0.67 g/kg in diet, 6 wk	[108]
Glucocorticoid-induced osteoporosis (rats)	Bone protection	Bone density of lumbar and femur were reversed, osteocalcin, sCa2+	-	OA	9 mg/kg, 14 d	[110]
Bone marrow macrophage (mice)	Inhibit osteoclastogen-esis	-	c-FOS, NFAT-c1, TRAP, CTSK,MMP-9	OA	10 mg/kg·2 d, 12wk	[111]
OVX- mice	Inhibit osteoclastogen-esis	-	NFAT-c1, c-FOS, MMP-9, CTSK, TRAP, CAR-2	OA	10 mg/kg·2 d,3 mo	[113]
Cartilage degeneration in osteoarthritis (rats)	Anti-cartilage damage	Collagen II	MMP-3, MMP-1, MMP-13, ADAMTS-4, -5,	OA	1-100 µmol/L, 50-100 µmol/L/rat single	[115]
Experimental periodontitis (mice)	Bone formation and remodeling through proper modulation of osteoblast and osteoclast	BMP-2,6,7; AXIN-2, β-CAT, LEFT, TWIST	IL-6,	OA-Xs	2µL (50 ng/µL)/d, 1-3 wk	[116]

OVX: Ovariectomised; OA: Oleanolic acid; TRAP: Tartrate-resistant acid phosphatase; CTSK: Cathepsin K; MMP: Matrix metalloproteinase; CAR: Constitutive androstane receptor; IL: Interleukin.