Table 1.
Neuroprotective and cognitive enhancement properties of compounds and extracts from the root of Angelica gigas.
| Compound/Extract | Model | Mechanism | Dose | References |
|---|---|---|---|---|
| ESP-102 (a combined ethanol extract, consists of A. gigas, Saururus chinensis and Schisandra chinensis) | Scopolamine-induced memory impairment in mice. Aβ25–35 or glutamate-induced neurotoxicity in cortical neurons of rats. | Enhances cognitive performances in the passive avoidance and Morris water maze tests. Protects against neuronal damage. | Mice: 1 to 100 mg/kg; Cell line: 0.001, 0.01 and 0.1 μg/mL |
[32] |
| Glutamate-induced toxicity in rat cortical cells. | Decreases [Ca2+]i, inhibits the production of NO and ROS. Increases SOD, GSH-px and GR. Maintains mitochondrial membrane potential. | 0.5 mg/mL to 50 mg/mL | [33] | |
| Scopolamine-induced memory impairment in rat hippocampus tissue | Antagonizes the preventative long-term potentiation effect. Increases BDNF and GluR-2 expressions. Acts on the AMPA/NMDA receptors. | 10 μg/mL | [34] | |
| LMK02 - Jangwonhwan (a herbal mixture of boiled extracts including A. gigas) | Aβ-induced neurotoxicity in H19-7 cells from rat hippocampus. | Protects against cytotoxicity. Inhibits formation of Aβ oligomer. Activates anti-apoptosis and decreases the production of ROS. | 1 to 100 μg/mL | [35] |
| Aβ-induced neurotoxicity in SH-SY5Y cells and Tg-APPswe/PS1dE9 mice. | Protects against cytotoxicity. Reduces Aβ1–42 and Aβ1–40 levels and β-amyloid plaque deposition in the brain. | Mice: 400 mg/kg, SH-SY5Y cells: 50 to 150 mg/mL |
[36] | |
| LMK03-Jangwonhwan (a combined boiled extract, consists of white Poria cocos and A. gigas) | Aβ-induced neurotoxicity in SH-SY5Y neuroblastoma cells and Tg-APPswe/PS1dE9 transgenic mice. | Protects against cytotoxicity. Reduces Aβ1–42 and Aβ1–40 levels and β-amyloid plaque deposition in the brain. | Mice: 300 mg/kg, SH-SY5Y cells: 50 and 100 mg/mL |
[37] |
| Fermented Bozhougyiqi-Tang (Herbal mixture) containing A. gigas | Scopolamine-induced memory impairments in mice and glutamate induced neurotoxicity in HT22 cells. | Protects against cytotoxicity. Enhances cognitive performance in the Morris water maze test. | Mice: 30, 100 and 200 mg/kg HT22 cells: 10, 100 and 1000 μg/mL |
[38] |
| Water extract of A. gigas root | Transient middle cerebral artery occlusion-induced focal cerebral ischemia in rats. | Decreases the brain infarction volumes and edema. Decreases the blood brain barrier permeability and neuronal death and inhibits the activation of astrocytes and microglia. Increases the expression of Ang-1, Tie-2, VEGF, ZO-1 and Occludin via activation of the PI3K/Akt pathway. Increases the expression of ICAM-1. | 10, 25, 50 and 100 mg/kg | [29] |
| Methanol extract of A. gigas root | Four-vessel occlusion-induced ischemia in rats. | Attenuates COX-2 induction in hippocampus. | 100, 250 and 500 mg/kg | [39] |
| Ethanol extract of A. gigas root | Aβ-induced memory impairment in mice. | Enhances cognitive performances in the passive avoidance performance and Y-maze tests. | Ethanol extract: 0.1% | [25] |
| Scopolamine/Aβ-induced cognitive dysfunction in mice. | Enhances cognitive performances in the passive avoidance and Morris water maze tests. Inhibits AChE activity. Attenuates the astrocyte activation and cholinergic neuronal damage in the hippocampus and the nucleus basalis of Meynert. | 150, 300, 600 and 1200 mg/kg | [40] | |
| LPS-induced neuronal injury in BV2 microglial cells and mice. | Inhibits NO release and suppressed the expressions of TNF-α and IL-1β, iNOS and COX-2. Attenuates neuronal damage in a hippocampal slice culture. Enhances cognitive performances in the passive avoidance and Y-maze tests. Suppresses the activation of microglia or astrocytes. | 0.05–2 μg/mL | [41] | |
| Ethanol extract of A. gigas root | Neuronal death in transient middle artery occlusion/reperfusion-induced ischemic rats and LPS-induced inflammatory response in BV2 microglia. | Decreases infarction volume in ischemic brains and inhibits the expression of iNOS, bax and caspase-3. Inhibits the production of NO, TNF-α and IL-6, and suppresses the expression of iNOS and COX-2. Attenuates phosphorylation of ERK1/2 and JNK MAPK in BV2 cells. | 50 and 100 mg/kg | [30] |
| Hot-melting extrusion -processed A. gigas/Soluplus | Scopolamine-induced memory disruption in mice. | Enhances cognitive performances in the Morris water maze and passive avoidance tests. | 200 mg/kg | [26] |
| Decursin | Scopolamine-induced amnesia in mice. | Enhances cognitive performances in the passive avoidance and Morris water maze tests. Inhibits AChE activity. | 1 and 5 mg/kg | [42] |
| Glutamate-induced toxicity in rat cortical cells. | Protects against cytotoxicity. Reduces [Ca2+]i in cortical cells. Increases the glutathione and GSH-px levels. | 0.1–10.0 μM | [43] | |
| Decursin | Aβ-induced neurotoxicity in PC12 cells. | Increases Nrf2 expression and suppresses the aggregation of Amyloid-β. | 0.01–10.0 μM | [44] |
| Aβ-induced neurotoxicity in PC12 cells. | Induces Nrf2 nuclear translocation, the upstream of HO-1 expression, ERK and dephosphorylated p38. | 0.01–10 μM | [27] | |
| Aβ-induced neurotoxicity in PC12 cells. | Protects against cytotoxicity and apoptosis. Reduces the mitochondrial membrane potential, ROS production, and mitochondrial release of cytochrome c. Suppresses the caspase-3 activity and moderated the ratio of Bcl-2/Bax. | 0.01–10 μM | [31] | |
| Decursinol | Aβ-induced memory impairment in mice. | Enhances cognitive performances in the passive avoidance and Y-maze tests. | 0.001%, 0.002%, and 0.004% | [25] |
| Glutamate-induced toxicity in rat cortical cells. | Protects against cytotoxicity. Reduces [Ca2+]i in cortical cells. Protects neurons against KA-induced neurotoxicity. Increases the glutathione and GSH-px levels. | 0.1–10.0 μM | [43] | |
| Decursinol angelate | Aβ-induced neurotoxicity in PC12 cells. | Increases Nrf2 expression and suppresses the aggregation of Aβ. | 0.1–10.0 μM | [44] |
| Nodakenin | Scopolamine-induced memory disruption in mice. | Enhances cognitive performances in the passive avoidance, Y-maze and Morris water maze tests. Inhibits AChE activity. | 10 mg/kg | [45] |
| Glutamate-induced toxicity in rat cortical cells. | Protects against cytotoxicity. | 0.1 to 10 μM | [46] | |
| 4″-Hydroxytigloyldecursinol, 4″-hydroxydecursin, (2″S,3″S)-epoxyangeloyldecursinol, (2″R,3″R)-epoxyangeloyldecursinol, Marmesinin, columbianetin-O-β-D-glucopyranoside | Glutamate-induced toxicity in rat cortical cells. | Protects against cytotoxicity. | 0.1 to 10 μM | [46,47] |
[Ca2+]i: intracellular calcium; AMPA/NMDA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-D-aspartate; VEGF: vascular endothelial growth factor; ZO-1: zonula occludens-1; ICAM-1: intercellular adhesion molecule-1; HO-1: heme oxygenase-1.