Therapeutic Potential of Saffron (Crocus sativus L.) in Ischemia Stroke

Table 1

Experimental studies assessing the effect of saffron and its bioactive ingredients on cerebral ischemic stroke.

Product	Animal type	Stroke model	Dose administration	Duration of administration	Major effects	References
Saffron hydroalcoholic extract	Male Sprague-Dawley rat	MCAO	30, 100, and 300 mg/kg/day orally	2 h at the first day and once daily from day 2 to day 42 after ischemia	(1) ↓Body weight loss, neurological deficit, spontaneous activity, infarct volume, and glial scar formation.	[20]
					(2) ↓GFAP, neurocan, and phosphocan in ischemic boundary zone.
					(3) ↓Contents of IL-6 and IL-1β in ischemic boundary zone.
					(4) ↑Content of IL-10 in ischemic boundary zone.
Saffron hydroalcoholic extract	Male Wistar rat	MCAO	100 and 200 mg/kg/day intraperitoneally	3 successive weeks before being subjected to left brain I/R and then administered four times (60 min before surgery, during the surgery, and 1 day and 2 days after the I/R)	(1) ↓Latency to move the body.	[40]
					(2) ↓MDA and NO in brain tissue.
					(3) ↑VEGF in brain tissue.
					(4) ↓BNP in brain tissue.
Crocin	Adult male SD rats of specific pathogen-free (SPF) grade	MCAO	50 and 100 mg/kg/day orally	7 days before MCAO induction	(1) ↓Neurological score, infarct volume.	[41]
					(2) ↓p-AMPK/AMPK, LC3-II/I, and ULK1 in brain tissues.
					(3) ↑p-mTOR/mTOR and p62 in brain tissues.
Crocin	C57BL/6J mice	Hypoxic-ischemic encephalopathy	5, 10, and 20 mg/kg	Every 12 h, starting immediately or at 2 h after hypoxia-ischemia.	(1) ↓Tissue loss and brain infarction.	[42]
					(2) ↓iNOS and COX-2 mRNA expression in the brain tissues-neurological function recovery.
Crocin	24-month-old male rat	MCAO	10, 20, 40, and 60 mg/kg, orally	Every two days for 2 months before induction of MCAO	(1) ↓Infarct volume.	[43]
					(2) ↑BBB integrity.
					(3) ↓Loss of tight junction proteins.
					(4) ↓Enhanced NADPH oxidase in brain tissues.
					(5) ↓MMP-2 and MMP-9 level in brain tissues.
Crocin	Adult female Sprague-Dawley rats	BCCAO	40 mg/kg/day orally	10 days before CCAO induction	(1) ↓Ischemic lesions.	[44]
					(2) ↓Hippocampal TUNEL-positive cells.
					(3) ↑TAS in brain tissues.
					(4) ↓OSI in brain tissues.
					(5) ↓Caspase-3 and HIF-1α in brain tissues
Crocin	Adult male Wistar rat	MCAO	15, 30, 60, and 120 mg/kg intraperitoneally	At the start and 1, 3, and 6 hours after MCAO induction	(1) ↓Neurological deficit and infarct volume.	[45]
					(2) ↑SOD, GPx, and TAC in the cortex of the brain tissue.
					(3) ↓Brain water content.
					(4) ↓MDA level in the cortex of the brain tissues.
Crocin	Adult male Wistar rat	MCAO	50 and 80 mg/kg intraperitoneally	At the start of ischemia	(1) ↓Neurological deficit and infarct volume.	[46]
					(2) ↓Axonal fragmentation, fiber demyelination, and prenecrotic neurons number.
Crocin	Male ddY mice	MCAO	10 mg/kg intravenously	Before and 3 hours after MCAO induction	↓Infarct volume.	[49]
Safranal	Adult male NMRI rat	Global cerebral ischemia was induced using the four-vessel occlusion method	727.5, 363.75, 145.5, and 72.75 mg/kg intraperitoneally	5 min prior to reperfusion and the administration was continued every 24 hours for 72 hours after the induction of ischemia	(1) ↓MDA level in brain tissues.	[51]
					(2) ↑Antioxidant capacity in brain tissues.
					(3) ↑Total thiol concentration in brain tissues.
Safranal	Adult male Wistar rat	MCAO	72.5 and 145 mg/kg intraperitoneally	0, 3, and 6 hours after induction of MCAO	(1) ↓Neurological score, infarct volume, and hippocampal cell loss.	[50]
					(2) ↓MDA level in brain tissue.
					(3) ↑Antioxidant capacity in brain tissue.

SD, Sprague-Dawley; MCAO, middle cerebral artery occlusion; BCCAO, bilateral common carotid artery occlusion; GFAP, glial fibrillary acidic protein; MDA, malondialdehyde; GPx, glutathione peroxidase; NO, nitric oxide; TAC, total antioxidant capacity; VEGF, vascular endothelial growth factor; BNP, brain natriuretic peptide; BBB, blood-brain barrier; ULK, Unc-51 like autophagy activating kinase; NADPH, nicotinamide adenine dinucleotide phosphate; MMP, matrix metallopeptidase; SOD, superoxide dismutase.