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

Table 2  In vivo anti-inflammatory effects and related mechanisms of action of oleanolic acid and its natural and synthetic derivatives (2014-2020)

Disease model/physiology	Effect	Mechanism		Compound	Dose	Ref.
		↑↑↑	↓↓↓
Ulcerative colitis (mice, DDS)	Anti-ulcerative colitis restoring the balance of Th17/Treg cells and inhibiting NF-κB signaling	FOXP-3, IL-10, ZO-1, Occludin, Claudin-1, pJNK, pP38	MPO, Th17, RORγt, IL-17, TNF-α, IL-1β, MAPK, pIKB, pTAK, pP65, iNOS, COX-2	OA	5-10 mg/kg·d, 3 d after DSS	[14]
Experimental mammary carcinogenesis	Anti-inflammatory	cP65, cIKB-α	COX-2, HSP90, NF-ĸB, npP65	OA-Xs	0.8-1.6 mg/kg·2 d, 2 wk before 16 wk after DSS	[15]
Colonic inflammation (mice, HFD)	Prevent colon inflammation	CD206, IL-10, #goblet cells	NF-қB, pNF-қB, IL-6, TNF-α, COX-2, KI67	OA-Xs (CDDO-Me)	10 mg/kg in drinking water, 21 wk	[16]
Ulcerative colitis (mice, DDS)	Anti-ulcerative colitis, anti-inflammatory via inhibiting STAT3	-	IL-17, STAT3	OA-Xs (CDDO-Im)	0.5-2 µmol/L	[17]
Anti-inflammation and antinociception (rats)	Anti-inflammatory, anti-nociceptive	Pain latency	Paw volume	OA-Xn	40 mg/kg once	[18]
Anti-inflammation (rats)	Membrane stabilization	-	Paw volume, hemolysis	OA-Xs	20-40 µg	[19]
Anti-inflammation (rats, hPMBCs)	Anti-inflammatory	-	COX-2, 5-LOX, NOS, MPO, edema, IL-6, NF-ĸB, PGE-2	OA-Xn	50 mg/kg, 100 µg	[20]
Anti-inflammation (mouse skin)	anti-inflammatory properties	-	IL-1α, IL-1β, IL-6, IL-23	OA-X	2 µmol	[21]
Allergic airway inflammation (rats)	Anti-inflammatory and immunomodulatory	IL-6, IL-8	DTH, NO, IL-4, 5, 13, 17, TLR2, NF-ĸB and TNF-α; sIgE, COX-2, and 5-LOX	Fe-OA and Zn-OA	2 mg/kg	[22]
Anti-inflammation and antinociception (mice)	Analgesic action and expressed strong anti-inflammatory activity	-	IL-6	OA-Xs, OA-ASA	0.3-300.0 mg/kg, p.o.	[23]
Lung injury (MLE-12, NDMA)	Anti-inflammatory, anti-oxidative stress and anti-apoptotic effects	SOD, GSH, SIRT-1, NRF-2, BCL-2,	TNF-α, IL-6, IL-1β, MDA, BAX, NF-ĸB, NRLP-3, LDH, Ac-P65, BAX/BCL-2	OA	10-20 mg/kg	[24]
Pulmonary inflammation and fibrosis (mice)	Anti-inflammatory response and anti- pulmonary fibrosis in the lungs	NLRP3	IL-1β, IL-6, TNF-α, TGF-β1, and fibronectin, NRLP-3, ASC, CASP-1	OA	0.001-1 mg/kg·d, 5 d (nc)	[25]
Subarachnoid haemorrhage (rats)	Alleviated SAH-induced vasogenic edema	VE-Cadherins, P120, ZO-1, Occludin-	HO-1	OA	5-20 mg/kg	[26]

DDS: Diaminodiphenyl sulfone; NF-κB: Nuclear factor-κB; JNK: cJUN NH₂-terminal kinase; IL: Interleukin; TNF-α: Tumor necrosis factor-α; OA: Oleanolic acid; OA-Xn: Natural derivatives of oleanolic acid; OA-Xs: Synthetic derivatives of oleanolic acid; HFD: High-fat diet; CDDO: 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid; CDDO-Me: C-28 methyl ester of CDDO; CDDO-Im: COOD-imidazole; STAT3: Signal transducer and activator of transcription 3; GSH: Glutathione; LDH: Lactic dehydrogenase; NRF-2: Nuclear factor erythroid-2-related factor 2.