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Treatment targets | Cell lines/animal models | Doses | Possible mechanism | References |
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Aβ aggregation and fiber formation | PC12 cells | 10 nmol/L | Inhibit fibrogenesis of Aβ and damage the formed Aβ fiber; reduce the accumulation of reactive oxygen; inhibit the aggregation and formation of the Aβ1-40 fiber | [20] |
PC12 cells | 1-100 μM | Inhibit Aβ40 fiber formation (IC50: 1.54-5.37 μM); damage the formed Aβ40 fiber (IC50: 5.00-5.19 μM); reduce the accumulation of reactive oxygen induced by Aβ25-35 aggregation | [21] |
SH-SY5Y-APPsw cells | 25 μM, 50 μM, 100 μM | Decrease the protein expressions of sAPPβ and β-site APP-cleaving enzyme 1; increase the levels of sAPPα and antidisintegrin and metalloprotease 10 | [22] |
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Aβ neurotoxicity | PC12 cells | 10 nmol/L, 100 nmol/L | Reduce toxicity of Aβ40 | [24] |
Injury model on primary rat cortical neuron using 5 μmol/L Aβ40 | 0.01 μg/L, 0.10 μg/L, 1.00 μg/L | Increase cell viability; dose-dependently reduce the release rate of LDH and NO; alleviate the toxicity of Aβ40 on the cortical neuron | [25] |
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Tau protein hyperphosphorylation | SH-SY5Y cells after incubation with 50 nmol/L OA for 36 h | 0.072 μg/mL, 0.72 μg/mL | Increase cell activity; reduce the proportion of apoptosis | [28] |
SH-SY5Y-APPsw cells | 50 μM, 100 μM | Increase phosphorylation at Ser9 of GSK-3β | [22] |
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Anti-inflammatory and antioxidant effects | Rats were intraventricularly injected with Aβ25-35 | 10 mg/kg | Decrease the number of microglia (OX-42 positive) and astrocytes (GFAP positive); decrease the mRNA expression of iNOS and COX-2 | [33] |
Mice model of traumatic brain injury | 25 mg/kg | Reduce expressions of proinflammatory cytokines TNF-α and IL-1β; increase the expression of anti-inflammatory factors IL-10 and TGF-β1 | [34] |
C57BL/6J mice was exposed to 500 nM Aβ | 50-400 μM | Alleviated intraneuronal glutathione (GSH) and lipid oxidation | [35] |
Microglia-neuron coculture system | 50 μM for anti-inflammatoryeffect; 0.5, 5, and 50 μM for antioxidant effect | Decrease the production of NO, TNF-α, and IL-1β; decrease the mRNA expressions of iNOS, TNF-α, and IL-1β; dose-dependently reduce the amount of production of ROS in microglia cells; inhibit the activation of transcription factor NF-κB in microglia | [36] |
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Apoptosis | PC12 cells treated with Aβ25-35 | 10 nmol/L, 100 nmol/L, 1 μmol/L | Reduce the proportion of apoptosis | [20, 41] |
SH-SY5Y cells exposed to MPP+ (500 μΜ) | 50 μM, 100 μM | Stabilization of mitochondrial membrane potential; decrease of apoptotic cell number and ROS production; inhibit the release of Cyt c and the activation of caspase-3; reduce bax expression to the normal level; reduce the ratio of bax/bcl-2 | [43] |
PD models of SH-SY5Y exposed to 6-OHDA (100 μM) for 12 h | 0.1 μM, 1 μM, 10 μM | Dose-dependently reduce the activity of caspase-3; inhibit the increase in bax and the decrease of bcl-2; increase the proportion of bcl-2/bax | [44] |
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Mitochondrial dysfunction | SH-SY5Y cells exposed to 6-OHDA | 0.1-10 M | Attenuate the decrease of mitochondrial membrane potential and increase of intracellular Ca2+ in a concentration-dependent manner | [44] |
Primary neurons of C57BL/6J mice exposed to Aβ | 50-400 μM | Suppress excess mitochondrial superoxide generation; protect mitochondrial bioenergetics against Aβ toxicity by preserving mitochondrial membrane potential and ATP production; rescue enzymatic activities of cytochrome c oxidase and F1FO ATP synthase; mitigate axonal mitochondrial fragmentation and increased dynamin-like protein 1 phosphorylation at Ser 616 | [35] |
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Neurogenesis | NSCs derived from the cortex of fetal mice | 20 μg/mL, 40 μg/mL | Promote the proliferation of NSCs; increase the number of NSCs and cultured neurospheres; promote NSCs to differentiate into neurons | [53] |
Neural stem/precursor cells (NSPCs) | 20 μM | Increase the survival rate of NSCs; maintain the self-renewal ability of NSCs by upregulating the mRNA expression of Nestin and Notch-1 | [54] |
Rats with middle cerebral artery occlusion | 1 mg/kg, 10 mg/kg | Increase the number of SVZ cells | [55] |
Bone marrow-derived neural stem cells (BM-NSCs) | 5 mg/mL, 20 mg/mL, 40 mg/mL | Promote nestin-positive BM-NSCs to mainly differentiate into NF-M-positive neurons and NG2-positive oligodendrocytes; few of them differentiated into GFAP-positive astrocytes | [56] |
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