Gastrodin, a Promising Natural Small Molecule for the Treatment of Central Nervous System Disorders, and Its Recent Progress in Synthesis, Pharmacology and Pharmacokinetics
Abstract
:1. Introduction
2. Synthesis of Gastrodin
2.1. Chemical Synthesis of Gastrodin
2.2. Biological Synthesis of Gastrodin
3. Pharmacological Effects of Gastrodin in the CNS
3.1. Sedative-Hypnotic and Sleep-Improving Effects
3.2. Anti-Epileptic Effect
3.3. Neuroprotective Effects
3.3.1. Anti-Inflammation
3.3.2. Antioxidation
3.3.3. Regulation of Neurotrophic Factors
3.3.4. Inhibition of Apoptosis and Autophagy
3.4. Effects on Neurodegenerative Diseases
3.4.1. Alzheimer’s Disease
3.4.2. Parkinson’s Disease
3.4.3. Others
3.5. Effects on Emotional Disorders
3.5.1. Anti-Depression
3.5.2. Anti-Anxiety
3.6. Effects on Cognitive Impairment
3.6.1. Vascular Dementia
3.6.2. Other Cognitive Impairment
4. Pharmacokinetic Characteristics of Gastrodin
4.1. Absorption
4.2. Distribution
4.3. Metabolism
4.4. Excretion
5. Conclusions and Prospects
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Model | Dose | Results | Reference |
---|---|---|---|
PTZ-induced epilepsy mice | 50, 100, 200 mg/kg | Ameliorate the intensity and increase the latency of seizure, improve the EEG pattern, inhibit IL-1β expression in microglia and modulate MKP-1/MAPK signalling. | [42] |
Pilocarpine-induced status epilepticus rats | 10 mM/day for 9 days | Reduce behavioural and electrographic severity of SE, reverse the increase in Nav1.6 expression in mEC Layer II and terminate bursting discharge, restore excitability of mEC Layer II stellate neurons. | [45] |
PTZ-induced epilepsy zebrafish | 600, 800, 1000 μM | Decrease seizure-like behaviour, extend the latency period and activate antioxidant genes via upregulation of Nrf2 to eliminate ROS. | [10] |
Lithium-pilocarpine induced epilepsy rats | 10, 20 mg/kg | Improve EEG signalling and cognitive behaviours, alleviate neural destruction, restore the expression of BDNF and NGF, and activate AMPK/PPARα pathway in model rats. | [43] |
Lithium-pilocarpine induced epilepsy rats | 50 mg/kg | Reduce the seizure severity, prevent the development of established status epilepticus, inhibit the epileptiform discharge and reverse the protein degradation of GABAA receptor α1 subunit. | [9] |
Effect | Model | Dose | Signalling Pathway | Reference |
---|---|---|---|---|
Anti-inflammation | LPS-exposed male C57BL/6 mice | 25, 50, 100 mg/kg/day for 10 days | Nrf2 signalling pathway | [47] |
AOH female SD rats | 10, 50 mg/kg/day for 2 weeks | p38 MAPK signalling pathway | [48] | |
LPS-induced SD postnatal rats | 50, 100, 200 mg/kg | Notch-1 and MAPKs signalling pathway | [49] | |
TBI male rats | 15, 30, 60 mg/kg/day for 7 days | NLRP3 inflammasome signalling pathway | [50] | |
LPS-stimulated BV2 microglia and postnatal rats | cells: 10, 20, 40, 80 μM rats: 100 mg/kg | Wnt/β-catenin signalling pathway | [51] | |
TBI male SD rats and LPS-induced BV2 microglia | rats: 100 mg/kg cells: 40 μM | PKA/CREB/BDNF pathway | [52] | |
LPS-stimulated microglial BV-2 cells | 30, 40, 60 μM | NF-κB and MAPK signalling pathway | [19] | |
H2O2-treated human SH-SY5Y cells | 1–25 μM | Nrf2 signalling pathway | [53] | |
LPS-activated BV-2 microglia | 0.17, 0.34 mM | RAS-Notch signalling pathway | [54] | |
Antioxidation | Pb-exposed male ICR mice | 50, 100 mg/kg/day for 4 weeks | Wnt/Nrf2 signalling pathway | [55] |
SAH male SD rats | 100 mg/kg | Nrf2/HO-1 antioxidant pathway | [56] | |
glutamate-induced rat PC12 cells | 0.1, 1.0, 10.0 μM | CaMKII/ASK-1/p38 MAPK/p53 signalling pathway | [57] | |
Regulation of neurotrophic factors | TBI male SD rats and LPS-induced BV2 microglia | rats: 100 mg/kg cells: 40 μM | PKA/CREB/BDNF pathway | [52] |
OGD-prepared TNC1 cells | 0.34 mM | Notch signalling pathway | [58] | |
Anti-apoptosis | MCAO-induced male SD rats | 15, 30, 60 mg/kg | apoptotic signalling pathways | [59] |
MCAO-induced male SD rats and Wister rats | 100 mg/kg | intrinsic apoptosis pathway | [60] | |
MCAO-injured male C57BL/6 mice | 50, 100, 200 mg/kg/day for 6 days | Wnt/β-Catenin and BCL-2 signalling pathway | [61] | |
Regulation of autophagy | LPS-exposed glial cells | 10 μM | BCL-2 and Bax signalling pathway | [62] |
METH-treated SH-SY5Y cells | 2, 4 mM | AKT/mTOR signalling pathway | [63] | |
Hypoxia-exposed HT-22 cells | 50, 100 μmol/L for 1.5 h | PI3K/AKT signalling pathway | [64] | |
CoCl2-induced HT-22 cells | 200 μM for 1 h | Ca2+/CaMKII signalling pathway | [65] |
Model | Dose | Reference | |
---|---|---|---|
AD | Aβ1–42-induced male SD rats | 10 mM | [79] |
Tg2576 transgenic mice | 60 mg/kg/day for 15 days | [80] | |
Aβ1–42-injected C57BL/6 mice | 60 mg/kg | [81] | |
Aβ1–42-induced male mice | 100 mg/kg/day for 15 days | [82] | |
Dgal-induced mice | 3, 90, 210 mg/kg/day for 9 weeks | [83] | |
Aβ1–42-induced BV2 mouse microglial cells | 10 μg/mL | [84] | |
Aβ1–42-induced rat hippocampal neurons | 1–100 μM | [85] | |
PD | rotenone-induced male Wistar rats | 0.2 g/kg | [86] |
rotenone-induced Lewis rats | 5 mg/kg | [87] | |
6-OHDA-induced male Wistar rats | 20, 40, 80 μg/3 μL/day for 5 days | [88] | |
MPTP-induced male C57BL/6 mice | 10, 30, 60 mg/kg/day for 15 days | [89] | |
MPTP-induced male C57BL/6 mice | 60 mg/kg/day for 2 weeks | [90] | |
MPTP-induced male C57BL/6 mice | 100 mg/kg/day for 19 days | [91] | |
6-OHDA-induced C. elegans | 0, 25, 50, 100, 200 μM | [92] | |
MPTP-induced SH-SY5Y cells | 1, 5, 25 μM | [89] | |
MPP+-induced human dopaminergic SH-SY5Y cells | 1, 5, 25 μM | [20] | |
Cerebral ischemia | MCAO-induced male SD rats | 10 mg/kg/day for 14 days | [93] |
MCAO-induced mice | 10, 50, 100 mg/kg | [94] | |
BCCAO-induced mice | 50, 100 mg/kg/day for 14 days | [95] | |
OGD/R-exposed NSCs | 0.01–1 μmol/L for 48 h | ||
OGD-exposed TNA2 cells | 10, 20, 50, 100 μM | [96] | |
ALS | ALS mice | 50, 200 mg/kg | [97] |
TBI | TBI male rats | 15, 30, 60 mg/kg/day for 7 days | [50] |
TBI male SD rats | 100 mg/kg | [52] | |
LPS-induced BV2 microglia | 40 μM |
Species | Mode of Administration | Dose | Cmax (μg/mL) | AUC (μg h/mL) | T1/2 (h) | Reference |
---|---|---|---|---|---|---|
Human | iv. | 600 mg | 94.66 ± 23.52 | 391.02 ± 81.88 | 4.16 ± 0.82 | [127] |
po. | 200 mg | 1.48 ± 0.28 | 7.21 ± 3.47 | 6.06 ± 3.20 | [128] | |
Dog | ig. | 40 mg/kg | 23.00 ± 4.39 | 121.75 ± 21.79 | 4.80 ± 2.26 | [129] |
Rat | in. | 50 mg/kg | - | 3.70 ± 0.54 | - | [130] |
iv. | 50 mg/kg | - | 43.30 ± 9.64 | - | ||
iv. | 20 mg/kg | 75.6 ± 6.63 | 22.3 ± 2.57 | 1.14 ± 0.380 | [131] | |
ig. | 40 mg/kg | 21.7 ± 6.90 | 18.1 ± 5.63 | 2.81 ± 2.25 | ||
ig. | 100 mg/kg | 44.84 ± 14.51 | 57.92 ± 11.94 | 1.13 ± 0.06 | [22] | |
ig. | 40 mg/kg | 21.74 ± 6.90 | 18.14 ± 5.63 | 2.81 ± 2.25 | [132] | |
iv. | 20 mg/kg | 75.65 ± 6.63 | 22.26 ± 2.57 | 1.14 ± 0.38 | ||
ig. | 21 mg/kg | 10.78 ± 0.95 | 9.45 ± 0.41 | 1.43 ± 0.67 | [133] | |
iv. | 21 mg/kg | - | 28.06 ± 2.39 | 1.30 ± 0.50 |
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Dai, Y.; Ban, W.; Yang, Z. Gastrodin, a Promising Natural Small Molecule for the Treatment of Central Nervous System Disorders, and Its Recent Progress in Synthesis, Pharmacology and Pharmacokinetics. Int. J. Mol. Sci. 2024, 25, 9540. https://doi.org/10.3390/ijms25179540
Dai Y, Ban W, Yang Z. Gastrodin, a Promising Natural Small Molecule for the Treatment of Central Nervous System Disorders, and Its Recent Progress in Synthesis, Pharmacology and Pharmacokinetics. International Journal of Molecular Sciences. 2024; 25(17):9540. https://doi.org/10.3390/ijms25179540
Chicago/Turabian StyleDai, Yanan, Weikang Ban, and Zhihong Yang. 2024. "Gastrodin, a Promising Natural Small Molecule for the Treatment of Central Nervous System Disorders, and Its Recent Progress in Synthesis, Pharmacology and Pharmacokinetics" International Journal of Molecular Sciences 25, no. 17: 9540. https://doi.org/10.3390/ijms25179540