Bioactive Compounds and Their Neuroprotective Effects in Diabetic Complications
Abstract
:1. Introduction
2. Causes of Diabetic Neuropathy and Related Pathophysiology
2.1. Hyperglycemia
2.2. Hyperlipidemia
2.3. Impairment of Insulin Signaling
3. Method of Literature Mining
4. Effect of Flavonoids on Neuronal Cell Death and Dysfunction
4.1. Baicalein
4.2. Chrysin
4.3. Diosmin
4.4. Epigallocatechin-3-Gallate
4.5. Hesperidin
4.6. Kaempferol
4.7. Luteolin
4.8. Myricetin
4.9. Naringenin
4.10. Proanthocyanidin
4.11. Puerarin
4.12. Quercetin
4.13. Rutin
4.14. Silibinin
5. Effect of Vitamins on Neuronal Cell Death and Dysfunction
5.1. Vitamin A
5.2. Vitamin C
5.3. Vitamin D
5.4. Vitamin E
6. Conclusions
Acknowledgments
Conflicts of Interest
References
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Bioactive Compounds | Models | Effects | Specific Mechanisms of Action | Reference |
---|---|---|---|---|
Flavonoids (Subclass) | ||||
Baicalein (flavones) | Primary rat cortical neurons | ↓Aβ-induced cell death | ↓12-lipoxygenase | [26] |
SH-SY5Y cells | ↓H2O2-induced cell death | ↓oxidative stress | [27] | |
Primary dopaminergic neurons | ↓LPS-induced cell injury | ↓NO, free radicals | [28] | |
STZ-induced diabetic mice | ↑nerve conductive velocity | ↓oxidative-nitrosative stress and p38 MAPK | [29] | |
Chrysin (flavones) | SH-SY5Y cells | ↓ER stress cell death | ↑mitochondrial membrane potential | [30] |
Primary microglia/microglia cell line | ↓LPS-induced NO, TNF-α and IL-1β | ↓JNK, NF-κB and CEBPβ | [31,32,33] | |
STZ-induced diabetic rats | ↑learning and memory function | ↑CAT, SOD, GSH/ ↓MDA | [34] | |
Diosmin (flavones) | PC12 cells | ↓LPS-induced apoptosis | ↓TNF-α | [35] |
High-fat diet-/STZ-induced diabetic mice | ↓glucose level and body weight ↑nerve function | ↓oxidative stress enzyme activity | [36] | |
STZ-/nicotinamide-induced diabetic mice | ↓glucose level | ↑antioxidants (vitamin c, vitamin E) and GSH | [37] | |
EGCG (flavanol) | Hippocampal neuronal cells | ↓Aβ-induced injury | ↑MDA and caspase activity | [38] |
STZ-induced diabetic rats | ↓hyperalgesia | ↓TBARS and NO ↑SOD | [39] | |
STZ-induced diabetic rats | ↓hypersensitivity | ↓oxidative stress damage | [40] | |
Hesperidin (flavanones) | PC12 cells | ↓Aβ-induced apoptosis | ↑GSK3β-mediated VDAC | [41] |
Cortical progenitors | ↓cell death | ↑PI3K and MAPK | [42] | |
STZ-induced diabetic rats | ↓hyperglycemia and hyperlipidemia ↑nerve function | ↓free radical generation and proinflammatory cytokines | [43] | |
STZ-induced diabetic mice | ↑nerve function | ↑AchE and GSH ↓TBARS, NF-κB, iNOS and COX-2 | [44,45] | |
Kaempferol (flavonols) | HT22 cells | ↓H2O2-induced apoptosis | ↓ROS production | [46] |
STZ-induced diabetic mice | ↓glucose level | ↓lipid peroxidation | [47] | |
Luteolin (flavones) | Primary cortical neurons | ↓Aβ-induced cell death | ↓ERK, JNK, p38 MAPK | [48] |
SH-SY5Y cells | ↑neurite outgrowth | ↑ERK-dependent Nrf2 pathway | [49] | |
STZ-induced diabetic rats | ↓neuronal injury ↑cognitive performance | ↓oxidative stress and ChE activity | [50] | |
STZ-induced diabetic rats | ↑nerve conduction | ↑Nrf2 and HO-1 | [51] | |
Myricetin (flavonols) | Rat cortical neurons | ↓Aβ-induced cell injury | ↓AGE | [52] |
Naringenin (flavones) | Primary microglial cells | ↓LPS-induced cytokine release | ↓p38 MAPK, STAT-1 ↑SOCS3 | [53,54] |
STZ-induced diabetic rats | ↓glucose level ↑NGF, IGF | ↑SOD, CAT, GPx | [55,56] | |
Proanthocyanidin (flavanols) | Mouse primary microglia cells and PC12 | ↓H2O2-induced cell death | ↓lactate dehydrogenase | [57,58] |
STZ-induced diabetic rats | ↓glucose level ↑nerve conductive velocity | ↑SOD, ↓AGE and MDA | [59] | |
STZ-/high carbohydrate-/high-fat diet-induced diabetic rats | ↓LDL ↑nerve conductive velocity | ↓ER stress protein | [60] | |
Aβ-induced diabetic mice | ↓neuronal apoptosis ↑synaptic density | ↑antioxidant level | [61] | |
Puerarin (isoflavones) | PC12 cells | ↓H2O2-induced cell death | ↑caspase-3, caspase-9 ↑SOD, GSHAKT/PI3K | [62,63] |
PC12 cells | ↓Aβ-induced cell death | ↑AKT/PI3K | [64] | |
Primary rat hippocampal neurons | ↓Aβ-induced oxidative stress | ↑Nrf-2/HO-1 | [65] | |
STZ-induced diabetic rats | ↓pain sensitivity | ↓inflammatory cytokines | [66] | |
Quercetin (flavonols) | SH-SY5Y cells | ↓H2O2-induced cell death | ↓KLF4 | [67] |
Dorsal root ganglion cells, primary Schwann cells and RSC96 cells | ↓high-glucose injury | ↑Nrf-2/HO-1, ↓NF-kB | [68,69] | |
Schwann cells | ↑growth ↓high glucose-induced damage | ↑autophagy | [69,70] | |
High-fat diet-induced diabetic mice | ↑cognitive function | ↓oxidative stress enzyme activity | [71] | |
Rutin (flavonols) | STZ-induced diabetic rats | ↓glucose level | ↓TBARS and lipid hydroperoxides | [72] |
STZ-induced diabetic rats | ↓glucose level ↑nerve function | ↑Nrf-2 | [73] | |
Silibinin | SH-SY5Y cells | ↓Aβ induced cytotoxicity | ↓oxidative stress | [74] |
Mouse cortical neurons | ↓H2O2-induced cell death | ↓beclin-1, LC3-II expression | [75] | |
db/db mice | ↓oxidative stress ↑DNA protection | ↑HO-1 | [76] | |
Vitamins | ||||
Vitamin A | Rat embryonic cortical neurons | ↑neurite outgrowth | ↑RAC1 | [77] |
SH-SY5Y cells | ↑neuronal differentiation | ↑glycolytic pathway and antioxidant pathway | [78] | |
Vitamin C | SH-SY5Y cells | ↓Aβ induced cytotoxicity | ↓oxidative stress | [79] |
Human brain pericytes | ↓high glucose induced apoptosis | ↓advanced glycation end production | [80] | |
Vitamin D | Primary astrocytes/C6 glioma cells | ↑NGF, GDNF and neurotrophin | - | [81,82,83] |
STZ-induced diabetic rats | no changes in glucose levels | ↑NGF level | [84] | |
Vitamin E | HT22 cells/rat cerebellar granule neurons | ↓Aβ- and H2O2-induced cell death | ↑NF-κB activity ↓HSP60 and vimentin | [85,86] |
Ex vivo embryo tissues | ↓high glucose-induced neuronal tube defect | ↑Pax-3 expression | [87] | |
STZ-induced diabetic rats | ↓reactive astrocytosis | ↓lipid peroxidation | [88] |
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Oh, Y.S. Bioactive Compounds and Their Neuroprotective Effects in Diabetic Complications. Nutrients 2016, 8, 472. https://doi.org/10.3390/nu8080472
Oh YS. Bioactive Compounds and Their Neuroprotective Effects in Diabetic Complications. Nutrients. 2016; 8(8):472. https://doi.org/10.3390/nu8080472
Chicago/Turabian StyleOh, Yoon Sin. 2016. "Bioactive Compounds and Their Neuroprotective Effects in Diabetic Complications" Nutrients 8, no. 8: 472. https://doi.org/10.3390/nu8080472