Table 1.
Comprehensive summary on the protective effects of black cumin against neurological and mental problems.
| Treatment with Doses | Experimental Model | Major Findings (Including Molecular Changes) |
References |
|---|---|---|---|
| Neuroinflammation | |||
| TQ (12.5 μM for 24 h) |
LPS/IFNγ or H2O2-activated BV-2 microglial cell | ↓H2O2; ↑GSH; ↑SOD and CAT | [32] |
| TQ (12.5 μM for 24 h) |
LPS/IFNγ or H2O2-activated BV-2 microglial cell | ↑Glutaredoxin-3, biliverdin reductase A, 3-mercaptopyruvate sulfurtransferase, and mitochondrial Lon protease; ↓IL-2, IL-4, IL-6, IL-10, and IL-17a, CFB, CXCL3 and CCL5 | [49] |
| TQ (2.5–10 μM) |
LPS-activated neuroinflammation in BV-2 microglial cell | ↓ROS; ↑LKB1 and AMPK; ↑nuclear accumulation of SIRT1 | [50] |
| Alzheimer’s disease | |||
| TQ (100 nM) |
Aβ1–42-induced neurotoxicity in hiPSC-derived cholinergic neurons | ↑GSH; ↓ROS; ↓synaptic toxicity, attenuate cell death and apoptosis | [51] |
| TQ fraction rich nanoemulsion of seeds (TQRFNE) (250 and 500 mg/kg BW) |
High fat/cholesterol diet-induced neurotoxicity in rats | ↓Aβ40 and Aβ42; ↑APP; ↓PSEN1 and PSEN2; ↓BACE1 and RAGE; ↑IDE and LRP1 | [52] |
| TQ fraction rich nanoemulsion of Nigella seeds (TQRFNE) (250 and 500 mg/kg BW) |
High fat/cholesterol diet-induced neurotoxicity in rats | ↓Memory impairment; ↓lipid peroxidation and soluble Aβ levels; ↑total antioxidant status and antioxidants genes expression | [53] |
| TQ (10, 20, and 40 mg/kg/day p.o. for 14 days) |
Combined AlCl3andD-Gal-induced AD in rats | Improved cognitive deficits; ↓Aβ formation and accumulation; ↓TNF-α and IL-1β; ↓TLRs pathway components; ↓NF-κB and IRF-3 mRNAs | [54] |
| TQ (intragastrically, 20 mg/kg/day once daily for 14 days) |
Combined AlCl3 and D-Gal induced neurotoxicity in rats | ↑ Memory performance; ↑ SOD; ↓TAC; ↓MDA; ↓NO; ↓TNF-α; ↓AChE activity; ↑BDNF and Bcl-2 | [55] |
| TQ (intragastrically, 20 mg/kg/day for 15 days) |
Aβ (1–42) infused rat model of AD | ↓Memory performance (Morris water maze test); ↓IFN-γ; ↑ DCX and MAP2 | [56] |
| Parkinson’s disease | |||
| TQ (100 nM) |
α-Synuclein-induced rat hippocampal and hiPSC-derived neurons | ↑Synaptophysin; ↓synaptic vesicle recycling; ↑spontaneous firing activity | [57] |
| TQ (10 mg/kg BW, 1 week prior to MPTP at 25 mg/kg BW) |
MPTP-induced mouse PD model | ↓MDA; ↑GSH; ↑SOD; ↑CAT; ↓IL-1β and IL-6; ↓TNF-α; ↓COX-2 and iNOS; ↓α-synuclein aggregation | [58] |
| TQ (7.5 and 15 mg/kg/day, p.o.) |
Rotenone-induced rat PD model | ↓Oxidative stress; ↑Parkin; ↓ Drp1; ↑dopamine; ↑TH levels | [59] |
| Ischemic stroke | |||
| Hydroalcoholic seed extract (20 mg/kg BW) |
Global ischemia in rats | ↓Brain edema and infarct volume; ↑VEGF, HIF and MMP9 | [60] |
| TQ | Stroke-prone spontaneously hypertensive rats | ↓Chemoattractant protein-1, Cox-2, IL-1β, and IL-6 | [61] |
| Traumatic brain injury | |||
| TQ (5 mg/kg/day for seven days) |
Feeney’s falling weight-induced moderate head trauma | ↑Neuron densities; ↓MDA | [62] |
| Anxiety and Depression | |||
| Ethanolic seed extract | Chronic stress-induced depression model | ↓NO | [63] |
| TQ-loaded solid lipid nanoparticle (20 mg/kg, p.o.) and TQ (20 mg/kg, p.o.) |
Chronic stress-induced depression model | ↓IL-6, TNFα; ↑BDNF; ↑5-HT; ↑IDO | [64] |
| NSO (0.2 mL/kg for 20 days) |
Stress-induced depression model | ↑Memory performance (FST) | [65] |
| Hydroalcoholic seed extract (200 and 400 mg/kg) |
Stress-induced depression and anxiety model | ↑Anxiolytic (Open field and elevated plus-maze test); ↓depression (FST) | [66] |
| Epilepsy | |||
| Ethanolic seed extract (400 mg/kg/day, p.o.) | PTZ-induced kindling mode | ↓Kindling development; ↑memory performance (Morris water maze test); ↓LTP | [67] |
| NSO (400 and 600 mg/kg BW) | Electroshock-induced seizures | ↑Anticonvulsant activity | [68] |
| TQ (10 mg/kg, i.p) |
Lithium chloride and pilocarpine-induced seizure | ↑Memory performance; ↑SOD; ↑Nrf2, HO-1 | [69] |
| TQ (10 mg/kg, i.p) |
Lithium chloride and pilocarpine-induced seizure | ↑Memory performance; ↓COX-2, TNF-α and NF-κB | [70] |
| Hydroalcoholic seed extract (200 and 400 mg/kg for 5 days) |
PTZ-induced seizure model | ↑Memory performance (Morris water maze and passive avoidance test); ↑ total thiol; ↓MDA | [71] |
| Schizophrenia | |||
| TQ (20 mg/kg, daily for 28 days, i.p.) |
Mice model of schizophrenia (haloperidol-induced catalepsy and apomorphine-induced climbing behavior) |
Anti-amnesic effect; ↓AChE activity; ↓ TBARS; ↑GSH and catalase; ↑dopamine level | [72] |
| Miscellaneous effects | |||
| Chemical-induced toxicity | |||
| TQ (5 mg/kg, i.p. for 11days) |
Acrylamide-induced neurotoxicity in rats | Improved gait abnormalities; ↑GSH; ↓MDA;↓caspases 3 and 9, and Bax/Bcl-2, pP38/P38 and pJNK/JNK; ↓pERK/ERK; restore BBB integrity | [73] |
| TQ (5 and 10 mg/kg, i.p., for 11 days) |
Acrylamide-Induced Peripheral Nervous System Toxicity in rats | Improved gait abnormalities; ↑GSH and ↓MDA;↓caspases 3 and 9, and Bax/Bcl-2, pP38/P38 and pJNK/JNK; ↓pERK/ERK | [74] |
| TQ (10 µM and 20 µM) |
Arsenic-induced cytotoxicity in SH-SY5Y cells | Promotes DNA repairing; ↓ROS, balanced transmembrane potential; ↓ Bax and PARP-1, and ↑Bcl-2 | [75] |
| TQ (5 mg/kg/day, for 3 days, p.o.) |
Arsenic-induced hippocampal toxicity in rats | Improve anxiety behavior (Open field test and elevated plus maze); ↑GSH and SOD; ↓DNA damage; ↓TNF-α and INF-γ | [76] |
| TQ (2.5 and 5 mg/kg BW, for 8 days, p.o.) |
Arsenic-induced hippocampal toxicity in Wistar rats | ↑Δψm | [77] |
| NSO (1 mL/kg BW for 7 days) |
Dichlorvos-induced oxidative and neuronal damage in rats | ↓Vacuolation in the frontal and cerebellar cortices;↑TAC and GSH↓ROS | [78] |
| Radiotoxicity | |||
| TQ | Radiation-induced oxidative stress in brain tissue | ↑Antioxidant enzymes | [79] |
p.o.: per os; BW: body weight.