Table 1.
Pre-clinical evidence supporting the neuroprotective effects of α- and β-asarone.
| In Vitro/In Vivo | Study Model | Main Mechanism | Dose and Route of Administration | Reference |
|---|---|---|---|---|
| α-asarone | ||||
| BV-2 | LPS/Parkinson’s disease (100 ng for 24 h) |
↓ Microglial activation ↓ Neuroinflammation ↓ NF-κB activation |
α-asarone (10, 50 and 250 µM., for 24 h) | [25] |
| PC12 and cultured rat astrocytes | tBHP/Dementia (0–300 μM., for 3 h) |
↑ Neurotrophic factors ↑ Neurogenesis ↑ Akt activation ↑ Antioxidant response ↓ Oxidative stress ↓ PKA signalling ↓ Apoptosis |
α- and β-asarone (15, 30 and 50 µM., 48 h) |
[43,73,74] |
| Wistar rat | Noise stress/Stress model (100 dBA/4 h/d for 30 days) |
↓ Oxidative stress ↓ AChE activity ↓ HSP70mRNA expression |
α-asarone (9 mg/kg−1, i.p., 30 days) | [75] |
| ICR mouse | Scopolamine hydrochloride/Alzheimer’s disease (2 mg/kg, i.p., for 2 days) | ↑ Motor performance ↓ Oxidative stress ↓ AChE activity |
α-asarone (3, 10 and 30 mg/kg, p.o., 15 days) | [76] |
| C57BL/6 mice | Nicotine/Stress model (10–200 µg/mL for 40 days) |
↑ Motor performance ↑ Neurotrophic factors ↑ p-CREB protein expression ↓ Weight loss |
α-asarone (5, 10 and 20 mg/kg, i.p., 8 days) | [77] |
| APP/PS1 transgenic mice | Submicron emulsion injection/Alzheimer’s disease | ↑ Motor performance ↑ Neuronal morphology ↑ Neuronal cell survival ↓ Neuroinflammation ↓ Aβ and tau aggregation ↓ Autophagosomes |
α-asarone (30 and 60 mg/kg, i.p., 3 months) | [28] |
| Wistar rat | LPS/Neurotoxicity (30 µg/paw., for 6 h) |
↑ Motor performance ↑ Cognitive function ↑ Anti-inflammatory ↑ Anti-nociceptive action ↓ Neuroinflammation ↓ LPS toxicity |
α-asarone (3, 10 and 30 mg/kg, p.o., for 7 h) | [78] |
| C57BL/6 mice | MPTP/Parkinson’s disease (18 mg/kg, i.p., four injections at 2 h intervals for one day) |
↑ Motor performance ↑ DA levels ↑ Cognitive function ↑ Anti-inflammatory ↑ TH-positive cells ↓ Neuroinflammation ↓ NF-κB activation |
α-asarone (10 mg/kg, p.o., 15 days) | [25] |
| C57BL/6J mice | Ethanol/Dementia (Saline, i.p. + 2 g/kg ethanol, i.g., treatment duration not mentioned) |
↑ Motor performance ↑ Cognitive function ↓ NMDA receptors ↓ SYNI activity ↓ Glu levels |
α-asarone (7.5, 15 and 30 mg/kg, i.p., treatment duration not mentioned) | [79] |
| Wistar rat | Submicron emulsion injection/Alzheimer’s disease | ↑ Motor performance ↑ Cognitive function ↑ Hippocampal neurons ↓ Aβ deposits |
α-asarone (10 and 25 mg/kg, i.p., for 28 days) | [80] |
| β-asarone | ||||
| PC12 | H2O2/Neurotoxicity (400 µM for 24 h) |
↓ Oxidative stress ↓ ROS production ↑ Nrf2 and HO-1 activation |
β-asarone (15, 30 and 60 µg/mL, for 24 h) | [71] |
| SH-SY5Y | Aβ/Alzheimer’s disease (SH-SY5Y, 20 μM for 24 h) |
↓ Oxidative stress ↓ ROS production ↓ Apoptosis ↑ ASK1 siRNA activity |
β-asarone (10–100 µg/mL, for 24 h) | [81] |
| SH-SY5Y | Aβ25-35/Alzheimer’s disease (20 μM for 24 h) |
↓ Oxidative stress ↓ ROS production ↓ Neuroinflammation ↓ Apoptosis ↑ Autophagy efficiency ↑ Bcl2 protein expression |
β-asarone (10, 50 and 100 µM, for 24 h) | [82] |
| Wistar rat | Middle cerebral artery occlusion (MCAO)/Ischemia | ↑ Motor performance ↓ Oxidative stress |
β-asarone (10, 20 and 30 mg/kg, p.o., for 30 days) | [83] |
| Wistar rat PC12 cells |
MCAO/Ischemia OGD/R for 24 h |
↑ Cell viability ↑ Motor performance ↓ Brain infarct volume ↓ Apoptosis ↓ Neuronal cell injury ↓ Neuroinflammation |
α-asarone (10 and 20 mg/kg, i.v., for 24 h) α-asarone (12, 24, 48 μM for 24 h) |
[84] |
| APP/PS1 transgenic mice | Alzheimer’s disease | ↓ Senile plaques ↓ Aβ40 and Aβ42 aggregation ↓ Autophagosomes ↑ p62 expression |
β-asarone (10, 20 and 40 mg/kg, i.g., for 30 days) | [85] |
| Wistar rat | 6-OHDA/Parkinson’s disease (4 mg/mL, 6 µL in each rat for 30 days) |
↑ DA levels ↑ TH-positive cells ↑ HSP70 expression ↑ p62 expression ↑ Neuronal cell survival ↓ α-synuclein ↓ Macroautophagy ↓ Autophagosomes |
β-asarone (15 mg/kg, i.g., for 30 days) | [29] |
| C57BL/6 mice | MK-801/Schizophrenia (0.1 mg/kg, i.p., for 7 days) |
↑ Motor performance ↑ Body weight ↑ Cognitive function ↑ Synaptophysin ↑ Postsynaptic density ↑ Cognitive function ↑ Anti-inflammatory ↓ Neuroinflammation ↓ Microglia activation |
β-asarone (25 mg/kg, i.g., for 14 days) | [86] |
| Wistar rat | CUMS/Depression (CUMS for 21 days) |
↑ Motor performance ↑ Body weight ↑ Cognitive function ↑ Neurogenesis ↑ BrdU-positive cells ↑ ERK1/2 activation ↑ CREB activation |
β-asarone (25 mg/kg, i.g., for 28 days) | [87] |
| PC12 | Aβ (1–42)/Alzheimer’s disease (20 μM for 24 h) |
↑ Cell viability ↑ Bcl2 protein expression ↓ Apoptosis ↓ JNK signalling |
β-asarone (7.5, 15, and 30 μg/mL, for 24 h) | [88] |
| Wistar rat | 6-OHDA/Parkinson’s disease (4 µg/µL, 6 µL in each rat for 28 days) |
↑ Motor performance ↑ DA levels ↑ TH-positive cells ↑ p62 expression ↑ Bcl2 expression ↓ α-synuclein ↓ Apoptosis ↓ JNK signalling |
β-asarone (10, 20, 40 and 75 mg/kg, i.g., for 28 days) | [89] |
| AβPP/PS1 double-transgenic mice | Alzheimer’s disease | ↑ Motor performance ↑ Cognitive function ↑ CREB activation ↑ Bcl2 expression ↑ CaMKII-α-positive cells ↓ Neuronal apoptosis |
β-asarone (7 and 21 mg/kg, i.g., for 4 months) | [90] |
↑ = increase, ↓ = decrease. i.p., intraperitoneal route; p.o., oral route; i.g., intragastrically; NF-κB, nuclear factor kappa B; PKA, protein kinase A; AChE, acetylcholinesterase; HSP70, heat shock protein 70; CREB, cAMP-response element-binding protein; p-CREB, phosphorylated CREB; Aβ, amyloid beta; LPS, lipopolysaccharides; DA, dopamine; TH, tyrosine hydroxylase; NMDA, N-methyl D-aspartate; ROS, reactive oxygen species; Nrf2, nuclear factor erythroid 2-related factor 2; HO-1, heme oxygenase-1; Bcl2, B-cell lymphoma 2; JNK, c-Jun N-terminal kinases; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 6-OHDA, 6-hydroxydopamine; CUMS, Chronic unpredictable mild stress; MCAO, middle cerebral artery occlusion; H2O2, hydrogen peroxide.