Table 4.

Pharmacological effects reported from Melissa officinalis extracts.

Effect	Model	Dosage or Concentration	Tested Systems	Results	Type of Extract	Reference
Antiproliferative	in vitro	20, 100, 250 μg/mL	Breast cancer cells MDA-MB- 231 and healthy HaCat cells	Inhibitory effect on migration and proliferation of both types of cells	ethanolic extract	[38]
	in vitro	50%	Human Colon Cancer Cell Line (HCT-116)	The 50 % ethanolic extract showed significant differences after 72 h of treatment, reducing cell proliferation to values close to 40%	ethanolic and aqueous extracts	[39]
Antitumor	in vitro	Different concentration	Human tumor cell lines: MCF-7, AGS and NCI-H460	Obtained revealed that the ethanolic extract presented the highest cell growth inhibitory potential in all the human tumor cell lines tested	ethanolic, methanolic, hydro-methanolic, hydro-ethanolic and aqueous extracts)	[40]
Antioxidant	in vitro	Different concentration	Encephalic tissue from male Wistar rats	Effective agent in the prevention of various neurological diseases associated with oxidative stress	ethanolic, methanolic and aqueous extracts	[41]
	in vitro	1, 2.5, 5 and 10 mg/mL	DPPH radical scavenging activity assay, β-carotene bleaching test and ABTS assay	Good antioxidant activity	essential oil	[42]
Antiangiogenic	in vitro, in ovo	50 μg/mL	Two breast cancer cell lines, MCF-7 And MDA-MB-231	Highest cell inhibitory activity was exhibited by the 96% ethanolic extract	ethanolic extracts and methanolic extracts	[4]
Cardioprotective	in vivo	25, 50 and 100 mg/kg b.w. * (4.23/8.46/16.91 mg/kg b.w. *)	Rats	Antioxidant and cardio-protective effects against arrhythmias induced by ischemia and ischemia-reperfusion	ethanolic leaf extract	[43]
Antinociceptive Antihyperglycemic	in vivo	0.01, 0.02 and 0.04 mg/day (0.0063/0.0126/0.0252 mg/kg b.w. *)	Male adult Wistar rats	Long-term oral administration of essential oil (at an effective dose of 0.04 mg/day) can suppress chemical hyperalgesia in diabetic rats	essential oil	[44]
Anxiolytic Antidepressant	in vivo	50, 75 and 150 mg/kg b.w./day * (3.91/5.86/11.72 mg/kg b.w. *)	Albino BALB/c male mice	Hydro-alcoholic extract (75 and 150 mg/kg) significantly reversed anxiety- and depressive-like behaviors	hydro-alcoholic extract	[45]
Neuroprotective	in vitro	5, 10, 50, 100, 500 μg/mL	Cortical neuronal Culture system	Protective effects on neurons in the brain	balm oil	[46]
	in vivo	50, 100, 200 and 400 mg/kg b.w. * (8.35/16.71/33.41/66.83 mg/kg b.w. *)	Male rats	Treatment with 100 mg/kg of oil attenuated the increased caspase-3 like protease activity significantly	balm oil	[46]
GABA-T inhibitor	in vitro	0–4 mg/mL	Rat brain	Phytochemical characterization of the crude extract determined rosmarinic acid as the major compound responsible for activity (40% inhibition at 100 μg/mL) since it represented approximately 1.5% of the dry mass of the leaves	methanol extract	[47]
Anti-kinetoplastidae	in vitro	31.25, 62.5, 125, 250 μg/mL	T. cruzi, L. brasiliensi, L. infantum	A potential source of natural product featuring anti-Leishmania and anti-Trypanosoma activity	ethanol extract	[48]
Analgesic	in vivo	5, 10, 20 mg/kg b.w. * (0.87/1.73/3.46 mg/kg b.w. *)	Male Wistar rats	Intrathecal administration could significantly improve hot-water and formalin-induced pain in male Wistar rats	hydro-alcoholic extract	[49]
Hypnotic	in vivo	200, 400 and 800 mg/kg b.w. * (14.81/29.61/59.23 mg/kg b.w. *)	Male Swiss mice	Extracts may be useful for insomnia	hydro-alcoholic extracts	[50]
Antidiabetic	in vivo	0.0125 mg/d	db/db mice	Anti-hyperglycaemic agent	essential oil	[51]
	in vivo	0.4%, 0.8% (w/w)	Otsuka Long-Evans Tokushima fatty rats	An effective therapeutic strategy to treat human obesity and type 2 diabetes	herbal extract	[52]
Anti-Alzheimer	in vitro	8.8 mg/mL	GSK-3Β, CK-1δ, and BACE-1	Best activity for ck-1δ inhibitory activity with maximum inhibitory concentration values at half (IC50) below 250 μg/mL	methanol extract	[53]
Antispasmodic	ex vivo	1, 5, 10, 25, and 50 mg/mL	Different segments of the gastrointestinal tract of mice	Site- and dose-dependent effects on the contractile activity of the gastrointestinal tract	hydro-ethanolic leaf extract	[54]
Antiviral	in vitro	1.5–150 μg/mL	RC-37 cells	High virucidal activity against HSV-1	aqueous extract	[55]
Antifungal	in vitro	15.5–2000 μg/mL	Human Pathogenic fungi	Good antifungal activity	ethanol extracts	[56]
		0.25–2 μL/mL	Phytopathogenic fungi in apples		essential oil	[57]
Antibacterial	in vitro	10 and 15 mg/mL	E. coli, L. monocytogenes, S. aureus and S. typhimurium	A significant antimicrobial effect	essential oil	[42]

* estimated human equivalent dose. b.w. = body weight.