Table 1.

In vivo studies towards memory and learning improvement by monoterpenes.

Monoterpene	In Vivo Model	Type of Test	Administration of Compound	Observations	Possible Mechanism of Action	References
thymol	Wistar Rats impaired with intrahippocampal injection of amyloid or intraperitoneal injection of scopolamine	Morris water maze task	intraperitoneally; 0.5, 1, or 2 mg/kg	Improvement cognitive functions; reversed negative effect of Aβ and scopolamine	Antioxidant and anti-inflammatory activity of thymol	[146]
carvacrol	Wistar Rats impaired with intrahippocampal injection of amyloid or intraperineal injection of scopolamine	Morris water maze task	intraperitoneally; 0.5, 1, or 2 mg/kg	Improvement cognitive functions; reversed negative effect of Aβ and scopolamine	Antioxidant and anti-inflammatory activity of carvacrol	[146]
	Sprague-Dawley rats with memory impairment and neuroinflammation gained by lipopolysaccharide injected into the lateral ventricle	Object recognition task; Morris water maze test	Intraperitoneally; 25 mg/kg, 100 mg/kg	Memory improvement; significantly attenuation of induced defects in cognitive functions	Attenuation of expression of inflammatory factors in the brain (interleukin-1β, taumor necrosis factor-α, cyclooxygenase-2). Increasing expression of brain-derived neurotropic factor mRNA and decrease expression of Toll-like receptor 4 mRNA.	[147]
	Male Wistar rats with memory impairment obtained by lead acetate drinking water	Morris water maze test	Orally; 25,50, and 100 mg/kg	Improvement of memory and learning	Decreasing lipid peroxidation and oxidation stress by improvement of activity of antioxidant enzymes (SOD, CAT, GPx)	[148]
linalool	C57BL/6J mice model anesthetized and stereotypically injected aggregated Aβ into hippocampus	Morris water maze test; passive avoidance test	intraperitoneally; 100 mg/kg	Cognitive improvement effect without negative influence on locomotor activity	Decreasing of apoptosis and oxidative stress induced by Aβ depending on Nrf2/HO-1 pathway	[104]
	Homozygous triple transgenic AD model (3xTg-AD) and nontransgenic (Non-Tg) mice	Morris water maze test	Orally, 25 mg/kg	reversion of cognitive and emotional deficits	antioxidant activity; decreasing of β-amyloid level	[102]
limonene	WKY and SHRsp rats with ischemia induced by occlusion of right middle cerebral artery—evaluation of influence of limonene on memory after stroke	Morris water maze test; novel object recognition test	Intraperitoneally; 20 mg/kg	protection against memory impairment	antioxidant effects through increasing SOD and CAT activities, decreasing MDA levels, increasing GSH levels and decreasing ROS levels.	[149]
α-pinene	scopolamine-induced memory deficit in C57BL/6 mice	Morris water maze test; passive avoidance test	Intraperitoneally; 10 mg/kg	memory enhancing activity and learning improvement	regulation of expression of proteins related to synthesis of acetylcholine and antioxidant defense system	[150]
α-terpinene	female Wistar rats	inhibitory avoidance task;	Orally; 0.5, 0.75 and 1.0 mL/kg	memory impairment	altering activity of enzymes responsible for neuronal plasticity and hydrolysis of ADP and ATP	[151]