Antioxidant and Anti-inflammatory Mechanisms of Neuroprotection by Ursolic Acid: Addressing Brain Injury, Cerebral Ischemia, Cognition Deficit, Anxiety, and Depression

Table 2

Effect of ursolic acid in behavioral animal models.

Model	Procedure	Dosage	Main outcome	Reference
Sedative, anticonvulsant, and analgesic effect	Lethality of pentylenetetrazol-induced seizures; writhing test and the hot-plate test of nociception in mice	2.3 or 20 mg/kg, p.o.	Inhibit the acetic acid-induced abdominal constriction; increase (higher dose) the reaction time in the hot-plate test; effect involves opioid receptors (reversed by naloxone)	Taviano et al. [74]
Antidepressant-like effect	Tail suspension test (TST) and the forced swimming test (FST) in mice	TST (0.01 and 0.1 mg/kg, p.o.) and in the FST (10 mg/kg, p.o.)	Reduce the immobility time in the TST and FST; effect abolished by a dopamine D(1) receptor antagonist (SCH23390)	Machado et al. [77]
Antidepressant-like effect	TST and FST; and open-field test (OFT) (locomotor activity) in mice	0.1 mg/kg, p.o.	No effect on locomotor activity; serotonergic and noradrenergic systems involved in the antidepressant-like effect (receptor antagonism study)	Colla et al. [78]
Anxiolytic-like effects	Open-field test, elevated plus maze test, light/dark box test, and marble burying test in mice	0.1, 1, and 10 mg/kg, p.o.	Anxiolytic-like effect (higher dose)—increased total time in the center, decreased number of rearing responses in the OFT, and an increased percentage of entries and total time spent in the open arms of elevated plus maze; no effect in the light/dark box and marble burying tests	Colla et al. [79]
Antinociceptive activity	Formalin or acetic acid-induced nociceptive response in mice	2 mg/kg, i.p.	Antinociceptive effect; effect mediated through cGMP; additive/synergism with 5HT1A receptors and antagonistic activity towards TRPV1 receptors	Verano et al. [80]
Antidepressant-like effects	TST in mice	0.1 mg/kg p.o.	Anti-immobility effect; effect abolished by the treatment of mice with H-89, KN-62, chelerythrine, U0126, or PD98059, but not with wortmannin or LY294002: activation of PKA, PKC, CAMK-II, and MEK1/2 mediate the antidepressant-like effects	Ramos-Hryb et al. [81]
Insomnia treatment	Pentobarbital-induced sleeping behaviors in mice	0.3 mg/kg, p.o.	Enhance sleep duration in pentobarbital-treated mice; effect attenuated by GABAA receptor antagonist (bicuculline)	Jeon et al. [87]