Disease-Modifying Activity of Huperzine A on Alzheimer’s Disease: Evidence from Preclinical Studies on Rodent Models
Abstract
:1. Introduction
2. Results
2.1. Study Selection
2.2. Study Characteristics
2.2.1. Animal Models
2.2.2. Behavioral Test Analysis
2.2.3. Neuroprotective Mechanisms Analysis
- (1)
- Inhibition of Aβ pathway
- (2)
- Enhancement of cholinergic activity
- (3)
- Other effects and mechanisms
2.3. Methodological Quality Assessment
Study | a | b | c | d | e | f | g | h | i | j | Scores |
---|---|---|---|---|---|---|---|---|---|---|---|
Cheng, D. H. 1998 [23] | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 3 |
Feng, J. H. 2017 [24] | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 |
Huang, D. B. 2013 [25] | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 |
Huang, X. T. 2014 [26] | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 |
Huang, Z. S. 2009 [27] | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 3 |
Liang, Y. Q. 2008 [28] | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 4 |
Nie, H. 2013 [29] | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 |
Rispoli, V. 2013 [30] | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 4 |
Teng, Y. 2014 [31] | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 3 |
Turkseven, C. H. 2017 [32] | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 |
Wang, C. Y. 2011 [33] | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 3 |
Wang, R. 2001 [34] | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 3 |
Wang, T. 1998 [35] | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 6 |
Wang, Y. 2012 [36] | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 3 |
Xiao, X. 2019 [37] | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 3 |
Xu, Z. W. 2006 [38] | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 4 |
3. Discussion
4. Materials and Methods
4.1. Search Strategy
4.2. Inclusion and Exclusion Criteria
- (1)
- Types of animals: laboratory animals of any breed, age, sex, or strain were included.
- (2)
- Types of involvement: the study must contain at least a control group and a Huperzine A administration group. The control group should include physiological saline or other solvent control.
- (3)
- Types of results: any results that reflected the effects of Huperzine A on Alzheimer’s disease models.
- (1)
- No access to the full text.
- (2)
- Reviews, case reports, comments, letters, and clinical trials.
- (3)
- Not testing the effect of Huperzine A on Alzheimer’s disease animal models.
4.3. Data Extraction and Quality Assessment
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Article | Animal Data | Administration of Hup A | Methods |
---|---|---|---|
Cheng, D. H. 1998 [23] | Sprague-Dawley rats (male, 280–350 g); i.c.v. AF64A 3 nmol/side | dosage: 0.3, 0.5, 0.8 mg/kg/day; ad: i.g.; duration: 3 weeks | behavioral test (radial maze test); biochemical experiments (choline acetyltransferase (ChAT) activity, acetylcholinesterase (AChE) activity, cholinesterase (ChE) activity) |
Feng, J. H. 2017 [24] | Sprague-Dawley (SD) rats (male and female, 3–4 months old, 250–280 g); Aβ40 peptide 10 μg injection into left hippocampal CA1 area | dosage: 40.5 μg/kg/day ad: i.g.; duration: 4 weeks | behavioral test (Morris water maze); hematoxylin-eosin staining (neuronal morphology); western blot (Cdk 5 protein); RT-qPCR (cdk5 mRNA); |
Huang, D. B. 2013 [25] | Wistar rats (male, 400–550 g, 10 months old); i.c.v. quinoline acid 150 nmol | dosage: 0.3 mg/kg/day; ad: i.p.; duration: 34 days; | behavioral test (morris water maze); biochemical experiments (acetylcholine and choline level, cholinesterase activity); tissue observation (hematoxylin and eosin staining of hippocampus) |
Huang, X. T. 2014 [26] | APPswe/PS1dE9 transgenic mice (2 months old) | dosage: 0.1 mg/kg/day; ad: i.g.; duration: 6 months | Immunohistochemistry (tau plaque); Aβ quantification; western blot (metal transporter with or without iron-responsive element); brain iron measurement |
Huang, Z. S. 2009 [27] | senescence-accelerated mouse prone/8 (SAMP8); normal control: senescence-accelerated mouse resistant 1 (SAMR1) | dosage: 0.02 mg/kg/day; ad: i.g.; duration: 50 days; | immunohistochemistry (Aβ expression in the cortex and hippocampus); RT-PCR (mRNA levels of BACE and APP) |
Liang, Y. Q. 2008 [28] | Sprague-Dawley rats (male, 250–300 g) 10 μg Aβ injection into nucleus basalis magnocellularis (NBM) | dosage: 012, 0.18 mg/kg; ad: i.g.; duration: 21 days | HPLC (ACh level detection, monoamine level detection); immunohistochemistry (detemine Aβ deposition) |
Nie, H. 2013 [29] | APPswe/PS1dE9 mice with C57BL/6J background (male and female, 30–35 g) | dosage: 0.25 mg/kg twice a day; ad: i.g.; duration: 4 weeks | behavioral test (independent activity test, Morris water maze); |
Rispoli, V. 2013 [30] | Wistar rats (male, 200–250 g, 3 months old); i.c. excitotoxic AMPA injection into NBM | dosage: 0.5 mg/kg; ad: i.p.; duration: 3 weeks | electroencephalogram (EEG) (theta rhythm); behavioral test (Morris water maze; Object recognition test (ORT)) |
Teng, Y. 2014 [31] | Kunming mice (male, 8–10 weeks old, 38–42 g) i.c.v. Aβ 25–35 10 μg induced AD model | dosage: 0.4 mg/kg; ad: i.g.; duration: 14 days | behavioral test (Morris water maze); ELISA [Aβ42, (ChAT), IL-6, TNF-α,receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF)]; Brain histopathology (neuronal damage); RT-PCR (β-actin, IL-6, RACK1 and BDNF); |
Turkseven, C. H. 2017 [32] | Sprague-Dawley rats (female, 13 weeks old, 180–200 g) 100 mg/kg/day d-galactose i.p. | dosage: 0.1 mg/kg/day; ad: i.p.; duration: 3 weeks | behavioral test (Morris water maze, open field test); electro-biophysical tests (extensor digitorum longus muscle contractile properties); immunohistochemistry (Aβ level); RT-PCR, ΔΔCT-PCR (several miRNA level) |
Wang, C. Y. 2011 [33] | APP/PS1 (APPswe/PSEN1dE9) transgenic mice; wild-type C57BL/6 mice (male, 6 months old) | dosage: 167, 500 μg/kg; ad: nasal; duration: 1 months | BrdU Staining (neurogenesis); Evan’s Blue Leakage Assay; AChE, ChAT, GSH-PX, CAT Activity; Immunohistochemistry and Confocal Laser Scanning Microscopy (distribution of Aβ in brain); RT-PCR (GAPDH, APP mRNA level); Sandwich Elisa |
Wang, R. 2001 [34] | Sprague-Dawley rats (male, 220–280 g) 800 pmol Aβ 40 i.c.v. at day 5, 8, 12 | dosage: 0.1, 0.2 mg/kg/day; ad: i.p.; duration: 12 days | neuron morphology (HE staining); TUNEL staining (detect apoptosis); immunohistochemistry (detect plaque); behavioral test (Morris water maze); measurement of ChAT activity |
Wang, T. 1998 [35] | Sprague-Dawley rats (male, 220–270 g) scopolamine 0.15 mg/kg i.p. induced memory impairment | dosage: 0.1, 0.2, 0.3, 0.4, 0.5 mg/kg; ad: p.o.; duration: 30 min before test; dosage: 0.05, 0.1, 0.2, 0.4 mg/kg; ad: i.p.; duration: 30 min before test | radial arm maze task; |
Wang, Y. 2012 [36] | APPswe/PS1dE9 transgenic mice (7 months old) high iron diet (2.5% carbonyl iron) | dosage: 0.1 mg/kg; ad: i.g.; duration: 5 months | Golgi staining (observe dendritic spine density); Thioflavin S Staining (assess the deposition of fibrous amyloid); Western blotting; Real-Time PCR Analysis; |
Xiao, X. 2019 [37] | APPswe/PS1dE9 transgenic mice (male, 2 months old, 20–30 g) | dosage: 0.1 mg/kg; ad: i.p. duration: 6 months | AChE activity measurement; cell viability; mitochondria activity (ROS level detection, ATP level detection, ABAD immunohistochemistry, cytochrome c release; western blot); measure the level and disposition of Aβ (thioflavin S immunostaining, ELISA quantity); |
Xu, Z. W. 2006 [38] | Kunming mice (male, 4 weeks old, 16–25 g) 4 mg/kg scopolamine-induced brain lesion | dosage: 0.1, 0.2, 0.3 mg/kg; ad: i.p.; duration: 30 min before test | behavioral test (step-through passive avoidance test, Y-water maze test) |
Model | Mechanism | Main Use | Disadvantages |
---|---|---|---|
AF64A induced | A cholinergic neuron-specific neurotoxin and an irreversible inhibitor of choline acetyltransferase | Studying of cholinergic damage as a similar characteristic of AD | Fail to reflect the typical pathological changes of AD senile plaques and NFTs |
AMPA induced | Cholinergic neuron toxicity | Simulating cholinergic damage of AD | Fail to reflect the typical pathological changes of AD |
quinolinic acid induced | Inducing tau phosphorylation | Simulating tau accumulation of AD | Acute toxicity model cannot simulate the progress of AD. |
Aβ induced | Aβ peptide-induced neurotoxicity | Studying of Aβ accumulation and toxicity of AD | A large amount of Aβ accumulates locally at the injection site Instead of spreading to the brain |
D-galactose induced | D-galactose induced glucose metabolism disorders and increasing free radical level | Studying mechanism of age-related diseases | The mechanism is unclear and cannot reflect pathological features well |
scopolamine induced | Non-selective cholinergic receptor blocker | Simulating cholinergic damage of AD | Lack of the characteristics necessary to study the pathophysiology of AD |
APPswe/PS1dE9 transgenic mice | Aβ plaques accumulation | Studying the role of APP and PSEN1 in the development of AD | Lack of neurofibrillary tangles and cost highly |
Senescence-accelerated mouse prone/8 (SAMP8) | Naturally occurring rapid aging | Studying mechanism of age-related memory defect | The short life is not suitable for long cycle experiment |
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Yan, Y.-P.; Chen, J.-Y.; Lu, J.-H. Disease-Modifying Activity of Huperzine A on Alzheimer’s Disease: Evidence from Preclinical Studies on Rodent Models. Int. J. Mol. Sci. 2022, 23, 15238. https://doi.org/10.3390/ijms232315238
Yan Y-P, Chen J-Y, Lu J-H. Disease-Modifying Activity of Huperzine A on Alzheimer’s Disease: Evidence from Preclinical Studies on Rodent Models. International Journal of Molecular Sciences. 2022; 23(23):15238. https://doi.org/10.3390/ijms232315238
Chicago/Turabian StyleYan, Ye-Piao, Jia-Yue Chen, and Jia-Hong Lu. 2022. "Disease-Modifying Activity of Huperzine A on Alzheimer’s Disease: Evidence from Preclinical Studies on Rodent Models" International Journal of Molecular Sciences 23, no. 23: 15238. https://doi.org/10.3390/ijms232315238