Table 2.
In vivo evaluation of the pharmacological properties of Crocus plant.
| Plant/compound/extract | Doses | Route | Model | Main pharmacological effect | Ref. |
|---|---|---|---|---|---|
| Crocetin | 100 mg/kg | Oral | Rats stroke-prone spontaneously hypertensive rats high-oxidative stress model | Antioxidant ↓oxidative stress, ↓ROS in rats brain |
[95] |
| Crocus sativus L./aqueous extract | 10, 20, and 40 mg/kg | i.p. | Rats STZ-induced diabetes |
Antihyperglycemic ↓blood glucose, ↓MDA, ↓NO, ↓lipids, ↓TG, ↓cholesterol, ↑glutathione level, ↑CAT, ↑SOD ↓inflammatory cytokines |
[180] |
| Crocus sativus L./aqueous, ethanol extracts | 500 mg/kg | i.v. | Rats, guinea pigs | Antihypertensive ↓blood pressure in a dose-dependent manner |
[100] |
| Crocetin | 20 mg/kg | Oral | Lung cancer-bearing mice benzo(a)pyrene- (B(a)p-) induced lung carcinoma | Antitumor ↑activities of enzymatic antioxidants ↑glutathione metabolizing enzymes |
[203] |
| Crocetin | 50 mg/kg | i.p. | Mice Benzopyrene-induced lung cancer model |
Antitumor ↓proliferating cells |
[204] |
| Zhejiang saffron | 100 mg/kg | Oral | Mice Xenograft tumor |
Antitumor ↓tumor size via caspase-3, caspase-8, caspase-9, and ↑apoptosis |
[205] |
| Saffron/aqueous infusion | 50-500 mg/kg | Oral | Mice DMBA-induced skin carcinogenesis |
Antitumor ↓papilloma cells formation |
[206] |
| Saffron/aqueous extract | 100 mg/kg | Topical | Mice DMBA, croton oil-induced skin carcinogenesis, MCA-induced soft tissue sarcomas |
Antitumor ↓tumor formation |
[207] |
| Saffron | 400, 800 mg/kg | Oral | Rats PTZ-induced seizures |
Anticonvulsant ↓seizures frequency in a dose-dependent manner |
[128] |
| Safranal | 0.15, 0.35 mL/kg | i.p. | Mice PTZ-induced seizures |
Anticonvulsant ↓seizures duration, delayed the onset of tonic convulsions |
[16] |
| Safranal | 72.75, 145.5, and 290 mg/kg | i.p. | Rats PTZ-induced seizures |
Anticonvulsant ↓MCS, ↓GTCS |
[17] |
| Crocin | 200 mg/kg | i.p. | Mice PTZ-induced seizures |
It did not show anticonvulsant activity | [16] |
| C. sativus L./hydroethanolic extract | 50 mg/kg | Oral | Meriones shawi Pb-intoxicated (25 mg/kg bw, i.p.) |
Neuroprotective ↑TH in SNC, VTA, LC, DS, and MFB ↑locomotor activity, ↓dysfunction in Pb-intoxicated meriones |
[141] |
| Crocetin | 25, 50, 75 μg/kg | i.p. | Rats 6-Hydroxydopamine (10 μg intrastriatal) Induced Parkinson's disease |
Neuroprotective ↓dopamine utilization by tissues |
[145] |
| Saffron | 0.01% w/v | Oral | BALB-c mice MPTP-induced Parkinson's disease |
Neuroprotective ↓ROS, ↑antioxidant effect → protect dopaminergic cells |
[146] |
| C. sativus L./stigma extract | 100 mg/kg | Oral | Rats Induction of cerebral ischemia MCAO |
Neuroprotective ↓SOD, ↓CAT, ↓Na+, and K+-ATPase activities ↓glutamate, ↓aspartate induced by ischemia |
[164] |
| Saffron/honey syrup | 200, 500 mg/kg | Oral | Mice Aluminum chloride-induced neurotoxicity |
Neuroprotective ↓neurotoxicity |
[208] |
| Saffron/aqueous extract | 50, 100, 200 mg/kg | Oral | Rats Diazinon- (20 mg/kg) induced neurotoxicity |
Neuroprotective ↓inflammation, ↓oxidative stress, and ↓neuronal damage |
[88] |
| Crocin | 30, 60, 120 mg/kg | Oral | Rats Ischemia/reperfusion injury model of stroke |
Neuroprotective Crocin 60 mg/kg → ↓brain oedema |
[158] |
| Crocetin | 50 mg/kg | Oral | Rats Induced cerebral contusion |
Neuroprotective ↑neurological function, ↓neuronal apoptosis ↑VEGFR-2, ↑SRF |
[155] |
| Crocin | 25, 50 mg/kg | i.p. | Rats Retinal damage induced by ↑intraocular pressure |
Retinal damage protection ↑RGCs, ↓apoptosis, and ↑PI3K/AKT |
[197] |
| Crocetin | 100 mg/kg | Oral | Mice N-Methyl-d-aspartate in the murine retina |
Retinal damage protection ↓NMDA, ↓GCL cell number, ↓TUNEL-positive cells, ↓b-wave amplitude, ↑caspase-3/7, and ↑caspase-3 in the GCL |
[195] |
| Saffron/aqueous extract | 50, 100, 150, and 250 mg/kg | i.p. | Rats | Effect on brain neurotransmitters ↑dopamine, ↑glutamate in a dose-dependent manner No effect on brain serotonin, norepinephrine |
[209] |
| Saffron/aqueous, ethanolic extracts | 80–320, 400–800 mg/kg | i.p. | Mice Naloxone-induced model |
Effect on opioid system ↓morphine withdrawal signs ↓locomotor activity (open-field test) |
[171] |
| Saffron/ethanolic extract safranal | 10, 50, and 100 mg/kg 1, 5, and 10 mg/kg |
i.p. | Mice | Effect on opioid system ↓acquisition, ↓expression of morphine conditioning place preference |
[210] |
| Crocin | 400, 600 mg/kg | i.p. | Mice | Effect on opioid system ↓acquisition, ↓reinstatement of morphine-induced conditioning place preference |
[211] |
| Crocus sativus L./ethanolic extract from stigma | 5, 10 μg/kg | Intra-accumbal | Rats | Effect on opioid system ↓time spent on the drug paired side, ↓expression of morphine conditioning place preference |
[212] |
| Crocus sativus L./aqueous, ethanolic extracts from stigma safranal crocin | Extracts 0.2-0.8 g/kg Safranal 0.15-0.5 mL/kg Crocin 50-600 mg/kg |
i.p. | Mice Forced open-field swimming test |
Antidepressant Extracts, safranal, crocin: ↓immobility time, ↑stereotypic activities Safranal: ↑swimming time Safranal and crocin: ↑climbing time Crocin: ↑dopamine, ↑norepinephrine Safranal: ↑serotonin |
[18] |
| Crocus sativus L./aqueous extract | 30 mg/kg | ICV | Rats STZ-ICV Alzheimer's disease model |
Anti-Alzheimer ↓cognitive deficits ↑learning, ↑memory via metabolism/enzyme mechanisms, no anatomical structural repair involved |
[136] |
| Saffron | 60 mg/kg | i.p. | BALB-c mice adult and aged | Cognitive enhancing effect ↑learning, ↑memory (passive avoidance behavior test) ↓AChE in adult mice No effect on AChE activity on aged mice |
[213] |
| Crocin | 30 mg/kg | ICV | Rats STZ-ICV Alzheimer's disease model |
Anti-Alzheimer ↑memory (passive avoidance test) ↑spatial cognition (Y-maze task) |
[137] |
| Crocin | 25-100 mg/kg | Oral | Rats Diet-induced hyperlipidemia |
Hypolipidemic
↑faecal excretion of fat and cholesterol Not influence the elimination of bile acids ↓pancreatic lipase as a competitive inhibitor |
[175] |
| Crocin safranal | 25, 50, and 100 mg/kg 0.5, 1, and 2 mg/kg |
i.p.l. | Rats Local inflammation induced by i.p.l. injection of carrageenan (100 μL, 2%) |
Anti-inflammatory ↓oedema, ↓inflammatory pain responses ↓neutrophils |
[214] |
| Crocus sativus L./ethanolic extract from stigma | 20, 40, and 80 mg/kg | Oral | Rats Alloxan-induced diabetes |
Antihyperglycemic 40 mg/kg: ↓blood glucose, ↑serum insulin |
[182] |
| Safranal | 0.2, 0.5, 0.75 mL/kg | Aerosol | Guinea pigs' citric acid aerosol for 10 min | Antitussive ↓cough count significantly as compared to the saline-treated group |
[189] |
Abbreviations and symbols: ↑ increase, ↓ decrease, body weight (bw), catalase (CAT), dimethylbenzene [a] anthracene (DMBA), dorsal striatum (DS), generalized tonic-clonic seizures (GTCS), intracerebroventricular (ICV), intraperitoneal (i.p.), intraplantar (i.p.l.), intravenously (i.v.), locus coeruleus (LC), 20-methylcholanthrene (MCA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), malondialdehyde (MDA), medial forebrain bundle (MFB), middle cerebral artery occlusion (MCAO), minimal clonic seizures (MCS), nitric oxide (NO), pentylenetetrazole (PTZ), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), reactive oxygen species (ROS), retinal ganglion cells (RGCs), serum response factor (SRF), substantia nigra compacta (SNc), superoxide dismutase (SOD), streptozotocin (STZ), triglycerides (TG), tyrosine hydroxylase (TH), ventral tegmental area (VTA), and vascular endothelial growth factor receptor-2 (VEGFR-2).