Table 7.
Characteristics of preclinical animal studies.
| Reference | Human Modeled Disease, Study Design and Population | Intervention | Comparator | Outcomes | |
|---|---|---|---|---|---|
| Primary | Secondary | ||||
| [33] | ●Nutritionally induced-cognitive dysfunction ●Young healthymale Crj:CD-1 (ICR) mice (3 weeks, n = 5) ●Long-term mono-level oral ad libitum intervention for 8 months. |
●Palm oil (5 g/100 g NRD) | ●100 g NRD | ●Slight (nonsignificant) improvement in cognitive functions as evidenced by the non-significant reduced escape latency. | |
| [32] | ●Diabetes-induced cognitive dysfunction ●Healthy male Wistar rats (age? n = 8). ●IP-injection of 45 mg/kg STZ (pH = 4.4, 0.1 M citrate buffer), while control was IP injected with citrate buffer vehicle. ●Long-term multilevel single oral daily intervention started from the 3rd day of STZ injection for 10 weeks. |
●25, 50 or 100 mg/kg of TRF triturated with 5% tween 80 and dissolved in 5 mL/kg doubled distilled water. (TRF: Purity and composition was not stated) | ●5% tween 80 in 5 mL/kg doubled distilled water | ●Significant dose-dependent improvement in cognitive dysfunctions as evidenced by the deceased transfer latency (the time to reach the platform) and increased the time spent in the target quadrant (improved memory consolidation after learning). ●A significant dose-dependent improve in the cerebrocortical cholinergic activity, while the hippocampal cholinergic function was not significantly improved. ●A significant dose-dependent reversal of the cerebrocortical and hippocampal oxidative stress through attenuating lipid peroxidation and enhancing the activity of the antioxidant enzymes. ●A significant dose-dependent anti-inflammatory effect though reducing the cerebrocortical and hippocampal levels of TNF-α, IL-1β and p56 subunit of NFκβ. ●A significant dose-dependent antiapoptotic effect through reducing cerebrocortical and hippocampal levels of caspase-3. |
|
| [32] | ●Normal cognitive function ●Healthy male Wistar rats with (age? n = 8–10). ●Long-term mono-level single oral daily intervention for 10 weeks. |
●100 mg/kg of TRF triturated with 5% tween 80 and dissolved in 5 mL/kg doubled distilled water. (TRF: Purity and composition was not stated) | ●5% tween 80 in 5 mL/kg doubled distilled water. | ●The cognitive performance was slightly (nonsignificant) increased as evidenced by the non-significantly reduced escape latency | |
| [36] | ●Diabetes-induced cognitive dysfunction ●Healthy male Wistar rats, (Age? n = 5–8) were intracerebroventricularly injected with of 2 µL of 3 mg/kg STZ (pH = 4.4 and 0.1 M of citrate buffer) in two divided doses (on day 1 and day 3), while the comparator rats were intraventricular injected with 2 µL of citrate buffer (pH = 4.4, 0.1 M). Post-operative, rats were orally fed on milk and allowed to feed on NRD (ad libitum) for 4 days followed by feeding on NRD up to the end of the treatment. ●Short-term multilevel single oral daily intervention started by the 1st day of injecting STZ to be continued for 21 days. |
●50 and 100 mg/kg α-TCT triturated with 5% tween and dissolved in double distilled water. | ●5% tween and dissolved in double distilled water. | ●A significant dose dependent improvement in cognitive functions as evidenced by the reduced escape latency. ●A significant dose-dependent reversal of neuro-oxidative stress through attenuating lipid peroxidation and enhancing of the activity of the antioxidant enzymes |
|
| [38] | ●Healthy cognitive function ●Healthy male Wister rats (age 3 months, n = 10) ● Long-term mono-level single oral daily intervention for 8 months. |
●200 mg/kg TRF in 5 mL/kg of distilled water (TRF: Purity and composition were not stated) | ●5 mL/kg distilled water | ●Significantly enhanced cognitive functions as evidenced by the reduced escape latency ●Significantly reduced plasma DNA damage ●Significant reversal of serum oxidative stress through increasing the activity of antioxidant enzymes |
|
| [34] | ●Nutritionally induced cognitive dysfunction. ●Healthy male Sprague-Dawley rats (age? n = 10) ●Long-term mono-level of ad libitum oral feeding on intervention admixed with palm oil base vehicle. ●Rats exposed to the same intervention levels during gestation, 2 weeks during lactation, 8 weeks after weaning. |
●100 mg/kg TRF suspended in 70 g/kg of palm oil base and admixed with 100 g NRD (TRF: Gold-Tri E ™70) | ●70 g/kg of palm oil base admixed with 100 g NRD. | ●Significant improvement in the cognitive functions of rats’ progeny ●Plasm and brain concentrations of tocotrienols indicated that α-TCT was the highest among the other isomers. |
|
| [37] | ●Chronic induced-stress condition ●Healthy male Sprague-Dawley rats (5 weeks, n = 9), which were stressed 5 h daily started from the 3rd week of intervention and continued for 21 days. ●Long-term mono-level single oral daily dose intervention for 5 weeks. |
●200 mg/kg of TRF in normal saline (TRF: Tocomin® SuprabioTM 20%) | Normal saline | ●Non-significant enhancement of the cellular proliferation and survival as well as expression of GAP-43 gene of granule cells in dentate gyrus | |
| [37] | ●Unstrained conditions ●Healthy male Sprague-Dawley rats (5 weeks, n = 9) ●Long-term mono-level single oral daily dose intervention for 5 weeks |
●200 mg/kg of TRF in normal saline (TRF: Tocomin® SuprabioTM 20% but compostion was not stated) | Normal saline | ●No significant alteration in the cellular proliferation and survival as well as expression of GAP-43 gene of granule cells in dentate gyrus | |
| [39] | ●Healthy cognitive function ●Healthy young male Wister rats (3 months, n = 9) ●Long-term mono-level oral single daily intervention for 3 months |
●200 mg/kg TRF in 5 mL/kg of olive oil (TRF = 149.2 mg/g α-tocopherol, 164.7 mg/g α-TCT, 48.8 mg/g β-TCT,213.2 mg/g γ-TCT and 171 mg/g δ-TCT). | 5 mL/kg of olive oil | ●No significant alteration in the cognitive functions as evidenced by the non-significant difference in escape latency. ●no significant alteration in plasma lipid peroxidation and the plasma activity of antioxidant enzymes ● A slight (nonsignificant) reduction in plasma DNA damage |
|
| [39] | ●cognitive dysfunction ●elderly male Wister rats (21 months, n = 9) ●Long-term mono-level oral single daily intervention for 3 months |
●200 mg/kg TRF in 5 mL/kg of olive oil (TRF = 149.2 mg/g α-tocopherol, 164.7 mg/g α-TCT, 48.8 mg/g β-TCT, 213.2 mg/g γ-TCT and 171 mg/g δ-TCT). | 5 mL/kg of olive oil | ●Significant Improved cognitive functions as evidenced by the significant reduction in escape latency. ●Reversal of the plasma oxidative stress through a significant attenuating lipid peroxidation and enhancing the activity of oxidative enzymes ● Significant attenuation of plasma DNA damage |
|
| [30] | ●Transgenic Alzheimer’s disease ●Heterozygous AβPP/PS1 double transgenic male mice (human chimeric amyloid expressing precursor protein and a mutant human presenilin 1 with deletion at exon 9), (5 months) ●Long-term mono-level single oral daily intervention for 10 months. |
●60 mg/kg of TRF in 5 mL/kg 12mg/mL vitamin-E-striped palm oil (n = 11) (TRF = 196.0 mg/g α-TCT, 24 mg/g β-TCT, 255 mg/g γ-TCT, 75 mg/gδ-TCT and 168 mg/g α-tocopherol) | ●5 mL/kg of 12 mg/mL of vitamin-E-striped palm oil (n = 10) | ●Slight (nonsignificant) enhancement of the recognition functions as evidenced by the nonsignificant increase in the recognition index, but the location preference was equivalent as evidenced by the equal spent time to explore the identical objects. ●A non-significant change in the levels of soluble and insoluble cortical or hippocampal Aβ isoforms (Aβ 40, Aβ 42 and Aβ oligomer). |
●A slight (nonsignificant) reduction in the hippocampal Aβ deposition, but significant reduction in the cortical Aβ deposition ●A significant reduction in cortical and hippocampal Aβ plaques |
| [35] | ●Transgenic Alzheimer’s disease ●Heterozygous AβPP/PS1 double transgenic male mice (human chimeric amyloid expressing precursor protein and a mutant human presenilin 1 with deletion at exon 9), (9 months, n = 4) ●Long-term mono-level single oral daily intervention for 6 months. |
●200 mg/kg TRF in 12 mg/mL vitamin E striped palm oil(TRF = f 24% α-tocopherol, 27% α-TCT,4% β-TCT, 32% γ-TCT,and 14% δ-TCT) | 12 mg/mL of vitamin E striped palm oil | Significant upregulation of genes responsible for neuroprotective effects such as Slc24a2, exo1 and Enox1 ●Significant downregulation of genes responsible for the pathology of AD such as Pla2g4a and Tfap2b |
|
| [31] | ●Transgenic Alzheimer’s disease ●Heterozygous AβPP/PS1 double transgenic male mice (human chimeric amyloid expressing precursor protein and a mutant human presenilin 1 with deletion at exon 9), (5 months, n = 9). ●Long-term mono-level single oral daily intervention for 10 months. |
●60 mg/kg TRF in 12 mg/mL of vitamin-E-striped palm oil(TRF = 23.40% α-tocopherol (23.40%),27.30% α-TCT; 3.34% β-TCT, 35.51% γ-TCT and 10.45% δ-TCT.) | ●5 mL/kg of vitamin-E-stripped palm oil | ●Slight (nonsignificant) enhancement of cognitive functions as evidenced by non-significantly reduced escape latency. | ●TRF could alter 90 putative metabolites involved in several metabolic AD-related pathways. |
AD: Alzheimer’s disease; TRF: Tocotrienol-rich fraction; MDA: malondialdehyde, TCT: tocotrienol, Aβ: amyloid-β protein, NRD: normal rodent diet, n: number of animals per group of either intervention or comparator, STZ: streptozotocin, ROS: reactive oxygen species, SOD: superoxide dismutase, CAT: Catalase, GPx: glutathione peroxidase; GSH: reduced glutathione, ?: not stated in the study, IP: intraperitoneal, Slc24a2: Solute carrier family 24 [sodium/potassium/calcium exchanger], exo1: Exonuclease 1, Enox1: Ecto-NOX disulfide-thiol exchanger 1, Pla2g4a: Phospholipase A2, group IVA [cytosolic, calcium-dependent], Tfap2b: Transcription factor AP-2 beta.