|
| Compound | Class of compound | Parkinson’s model | Mechanisms | References |
|
| Acetyl-L-carnitine | Quaternary ammonium | In vitro human neuroblastoma SK-N-MC cells model of rotenone-induced PD | Maintenance of mitochondrial integrity and function:
↑ mitochondrial biogenesis
↓ ROS generation | [65] |
|
| Astaxanthin | Nonprovitamin A carotenoid | MPP(+)-induced mouse model
In vitro human neuroblastoma SK-N-SH cells model of MPP+-induced PD | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax and α-synuclein
↓ caspase-3 | [81] |
|
| | | In vitro human neuroblastoma SH-SY5Y cells model of 6-OHDA-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential;
maintain mitochondrial redox activity | [82] |
| Baicalein | Flavonoid | In vitro rat adrenal pheochromocytoma PC12 cells model and isolated rat brain mitochondria of rotenone induced PD | Inhibition of the mitochondrial apoptotic pathway:
↓ caspase-3 and caspase-7
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ intracellular ATP production | [83] |
| | | In vitro human neuroblastoma SH-SY5Y cells model of 6-OHDA-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
Inhibition of the mitochondrial apoptotic pathway:
↓ caspase-3 and caspase-9
↓ p-c-Jun N-terminal kinase (JNK) | [84] |
|
Caffeic acid
phenethyl ester |
Phenolic compound | 6-OHDA-induced rat PD model | Inhibition of the mitochondrial apoptotic pathway:
↓ caspase-3 and caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function | [85] |
| Primary cultures of cerebellar granule neuron 6-OHDA-induced PD | Inhibition of the mitochondrial apoptotic pathway,
↓caspase-3
↓ cytochrome c release | [86] |
|
| CNB-001 | Pyrazole derivative of curcumin | MPTP-induced rodent PD model | Maintenance of normal mitochondrial morphology and size | [87] |
| In vitro human neuroblastoma SK-N-SH cells model of rotenone-induced PD | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3 and caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential | [88] |
|
|
Curcumin |
Polyphenol | PC12 cells mutant A53T α-synuclein-induced cell death | Inhibition of the mitochondrial apoptotic pathway:
↓ caspase-3 and caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation | [89] |
| Mouse brain and the 1RB3AN27 (N27) rat dopaminergic neuronal cell line model of buthionine sulfoximine-induced PD | Maintenance of mitochondrial integrity and function:
↑ activities of complex I
↓ oxidative damage to proteins
↑ glutathione | [90] |
|
| DL-3-n-butylphthalide (NBP) | Synthetic compound based on L-3-n-butylphthalide | In vitro rat adrenal pheochromocytoma (PC12) cells model of MPP(+)-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ glutathione | [91] |
|
| Echinacoside | Phenylethanoid glycoside | In vitro rat adrenal pheochromocytoma (PC12) cells model of H2O2-induced PD | Inhibition of the mitochondrial apoptotic pathway | [92] |
|
| Edaravone | Pyrazole derivative | Rotenone-induced rat PD model | Inhibition of the mitochondrial apoptotic pathway:
↓ Bax
Maintenance of mitochondrial integrity and function:
↓ ROS generation | [93] |
|
| Esculetin | Coumarin | MPTP-induced mice PD model | Inhibition of the mitochondrial apoptotic pathway:
↓ caspase-3 | [94] |
|
| Ginsenoside Re | Panaxatriol saponin | PINK1 null cells | Reversing the deficit in complex IV activity:
↑ LRPPRC, Hsp90, and Hsp60 levels | [95] |
|
| Glutamoyl diester of curcumin | Polyphenol | Mouse brain mitochondria induced-peroxynitrite PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation | [96] |
|
| Harmalol | Beta-carboline | In vitro rat adrenal pheochromocytoma (PC12) cells model of SNAP-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation | [97] |
|
| Harmine | Beta-carboline | In vitro rat adrenal pheochromocytoma (PC12) cells model of SNAP-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation | [97] |
|
| Hesperidin | Polyphenol | In vitro human neuroblastoma SK-N-SH cells model of rotenone-induced PD | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3 and caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ glutathione | [98] |
|
| Isoborneol | Monoterpenoid alcohol | In vitro human neuroblastoma SH-SY5Y cells model of 6-OHDA-induced PD | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3
↓ cytochrome c release | [99] |
|
| Kaempferol | Flavonoid | In vitro human neuroblastoma SH-SY5Y cells model and primary neurons of rotenone-induced PD | ↑ Autophagy | [100] |
|
| α-Lipoic acid |
Organosulfur compound derived from octanoic acid | In vitro rat adrenal pheochromocytoma PC12 cells model of MPP(+)-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation | [75] |
| Rotenone-induced rat PD model | Maintenance of mitochondrial integrity and function:
↑ mitochondrial complex I activity
↑ glutathione | [76] |
| In vitro human neuroblastoma SK-N-MC cells model of rotenone-induced PD | Maintenance of mitochondrial integrity and function:
↑ mitochondrial biogenesis
↓ ROS generation | [77] |
| In vitro rat adrenal pheochromocytoma (PC12) cells model of PD | Maintenance of mitochondrial integrity and function:
↑ mitochondrial complex I activity
↑ glutathione | [78] |
|
|
Lycopene |
Carotenoid | In vitro human neuroblastoma SH-SY5Y cells model of MPP(+)-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↓ lipid peroxidation
↑ intracellular ATP production
↑ mitochondrial DNA copy numbers and mitochondrial RNA transcript levels | [101] |
| Rotenone-induced rat PD model | Inhibition of the mitochondrial apoptotic pathway:
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
↓ lipid peroxidation
↑ SOD activity
↑ glutathione | [102] |
|
| | | MPTP-induced mice PD model | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↑ antioxidant enzyme levels
↑ intracellular ATP production | [67] |
| | | Rotenone-induced rat PD model | Maintenance of mitochondrial integrity and function:
↓ ROS generation
↑ glutathione
↑ SOD and catalase activities | [68] |
| Melatonin | Hormone | Rotenone-induced isolated rat brain mitochondria PD model | Maintenance of mitochondrial integrity and function:
↓ Ca2+ levels
↓ ROS generation | [69] |
| | | 6-OHDA-induced rat PD model | Maintenance of mitochondrial integrity and function:
↑ mitochondrial complex I activity | [70] |
| | | MPP(+)-induced isolated rat liver mitochondria and striatal synaptosomes PD model | Maintenance of mitochondrial integrity and function:
↑ mitochondrial complex I activity | [71] |
|
MitoQ (mitoquinone
mesylate) | — | In vitro human neuroblastoma SH-SY5Y cells model of 6-OHDA-induced PD | Inhibition of the mitochondrial apoptotic pathway:
↓ Bax
↓ Drp1 | [73] |
|
| N-Acetylcysteine | Amino acid derivative | H2O2 and toxic quinones derived from dopamine-induced rat PD model | Maintenance of mitochondrial integrity and function:
↑ mitochondrial respiratory activity
↑ Na+, K+-ATPase activity | [103] |
|
| Neuropeptide cocaine and amphetamine regulated transcript (CART) | Peptide | In vitro human neuroblastoma SH-SY5Y, HEK293 cells, and cultures of cortical and hippocampal neurons of H2O2-induced PD | Maintenance of mitochondrial integrity and function: protection of mitochondrial DNA (mtDNA), cellular proteins, and lipids | [78] |
|
| Osthole | Coumarin | In vitro rat adrenal pheochromocytoma (PC12) cells model of MPP(+)-induced PD | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3
↓ cytochrome c release | [104] |
|
| Piperine | Alkaloid | 6-OHDA-induced rat PD model | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3 and caspase-9
↓ cytochrome c release | [105] |
|
| Polyhydroxylated fullerene derivative C(60)(OH)(24) | — | In vitro human neuroblastoma cells model of MPP(+)-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ activities of complexes I and II
↓ oxidative damage to DNA and proteins | [106] |
|
| Protocatechuic acid | Polyphenol | In vitro rat adrenal pheochromocytoma (PC12) cells model of MPP(+)-induced PD | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ caspase-3
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ glutathione | [107] |
|
|
Pyruvate |
Organic acid | In vitro human neuroblastoma SK-N-SH cells model of H2O2-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation | [79] |
| In vitro rat adrenal pheochromocytoma (PC12) cells model of dopamine-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↓ p53
↓ nuclear translocation of NF-kappaB
Inhibition of the mitochondrial apoptotic pathway | [80] |
|
|
Quercetin |
Bioflavonoid | Rotenone-induced rat PD model | Maintenance of mitochondrial integrity and function:
↓ ROS generation
maintain mitochondrial membrane potential | [108] |
| In vitro glial-neuronal system model of MPP(+)-induced PD | Maintenance of mitochondrial integrity and function:
↓ inducible nitric oxide synthase protein expression
↓ superoxide radicals | [109] |
|
| Rapamycin | Macrolide | 6-OHDA-induced rat PD model | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
↓ lipid peroxidation
↑ SOD and GSH-PX | [110] |
|
| Resveratrol | Polyphenol | In vitro primary fibroblasts cultures from patients with parkin mutations (PARK2) | Maintenance of mitochondrial integrity and function:
↑ complex I activity
↑ citrate synthase activity
↑ basal oxygen consumption
↑ mitochondrial ATP production
↓ lactate content | [111] |
|
| Rosmarinic acid | Polyphenol | In vitro MES23.5 dopaminergic cells model of 6-OHDA-induced PD. | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation | [112] |
|
| Salvianic acid A | Polyphenol | In vitro human neuroblastoma SH-SY5Y cells model of MPP(+)-induced PD | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax | [113] |
|
| Salvianolic acid B | Polyphenol | In vitro human neuroblastoma SH-SY5Y cells model of 6-OHDA-induced PD | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3
↓ cytochrome c release | [114] |
|
| Sesamin | Lignan | In vitro glial-neuronal system model of MPP(+)-induced PD | Maintenance of mitochondrial integrity and function:
↓ inducible nitric oxide synthase protein expression
↓ superoxide radicals | [22] |
|
| Tetramethylpyrazine | Pyrazine | MPTP-induced rat PD model | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3
↓ cytochrome c release | [115] |
|
| Tyrosol | Phenolic compound | MPP(+)-induced CATH.a cells PD model | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential;
maintain intracellular ATP production
Inhibition of the mitochondrial apoptotic pathway:
(i) activation of PI3K/Akt signalling pathway | [116] |
|
| Umbelliferone | Coumarin | MPTP-induced mice PD model | Inhibition of the mitochondrial apoptotic pathway:
↓ caspase-3 | [94] |
|
Ursodeoxycholic
acid | Secondary bile acids | In vitro human neuroblastoma SH-SY5Y cells model of SNP-induced PD | Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3, caspase-7, and caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ glutathione | [74] |
|
| Xyloketal B | Triterpenoid | In vitro rat adrenal pheochromocytoma (PC12) cells model and Caenorhabditis elegans of MPP(+)-induced PD | Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ glutathione | [117] |
|
