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

Table 3  In vivo neuroprotective 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.
		↑↑↑	↓↓↓
Focal brain hypoxia (rats)	Neuroprotective, IBI, decreased neural damage suppressing glial activities	S-100b, MAP-2	GFAP, NADP-Diaphorase, iNOS	OA	6 mg/kg·d, 6 d	[30]
Parkinsonian model (rats)	Prevents AIM, anti-PD, ameliorated dyskinesis	CAT	Affected limbs, AIMs, ROS	OA	100 mg/kg·2 d, 8 d	[31]
Neuro-degeneration (rats, hydroxydopamin)	Protects against neurodegeneration	Cerabral doapamine, contralateral limb use		OA	100 mg/kg·2 d, 7 d pre or post	[32]
Brain damage (rats, fluoride)	Brain damage	GSH, SOD, CAT, GPX, GST, GR	sALT, sAST, LPO, NO	OA	5 mg/kg·d, last 14 d,	[33]
Alzheimer’s disease model (rats, Aβ25-35)	Anti-alzheimer, increased synaptic plasticity, decreased Aβ25-35 toxicity	NMDAR-2B, CREB	CaMKII, PKC, BDNF, TRK-B, Ca2+, Latency time	OA	21.6 mg/kg	[34]
Rat coronal brain slice	Neuroprotective, anti-alzheimer,	BDNF	APP (TAU) toxicity,	OA-Xn		[35]
Cognitive dysfunction (mice)	Ameliorates cognitive dysfunction	pERK-1,2; pCREB, BNDF, TRK-B	-	OA	0.625-5 mg/kg	[36]
Chronic unpredictable mild stress (mice)	Anti-deprassant	pERK-1,2; pCREB, BNDF, miR-132, PSD-95, SYN-1	-	OA	2.5-40 mg/kg·d	[37]
Cerabral IRI (mice, PC12 cells)	Cerabral protection and prevent IRI	Body weights, sTG, pAMPK, pGSK-3β, APN, Adipo-R1, Adipo-R2, pLKB-1, MAO	sGLU, sINS, Neurological scores, BAX/BCL2, MDA, TNF-α, IL-6, CASP-3,	OA-X (CHS)	pretreatment 30,60, 120 mg/kg·d	[38]
Exprerimenal stress (mice, corticoid)	Anti-depressant	AKT/mTOR, BNDF	SGK1, GR	OA	10 mg/kg	[39]
Mice	Anti-depressant	-	MAO-A	OA	0.1 mL/10g	[40]
Mice	Anti-depressant	BNDF, sleep duration	Behavioral tests, MAO	OA	5-40 mg/kg	[41]

OA: Oleanolic acid; GFAP: Glial fibrillary acidic protein; APP: Amyloid precursor protein; AIM: Abnormal involuntary movements; CREB: cAMP response element-binding; GSH: Glutathione; ERK: Extracellular-signal-regulated kinase; IRI: Ischemia-reperfusion injury; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.