Effects of Phenylethanoid Glycosides Extracted from <i>Herba Cistanches</i> on the Learning and Memory of the APP/PSI Transgenic Mice with Alzheimer’s Disease

Yang, Jianhua; Ju, Bowei; Hu, Junping

doi:https://doi.org/10.1155/2021/1291549

BioMed Research International

On this page

Abstract Background Methods Results Discussion Abbreviations Data Availability Ethical Approval Conflicts of Interest Authors’ Contributions Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2021 | Article ID 1291549 | https://doi.org/10.1155/2021/1291549

Effects of Phenylethanoid Glycosides Extracted from Herba Cistanches on the Learning and Memory of the APP/PSI Transgenic Mice with Alzheimer’s Disease

Jianhua Yang,¹Bowei Ju,^2,3and Junping Hu²

Academic Editor: Wen Quan Zou

Received21 Jul 2020

Revised30 Nov 2020

Accepted05 Jan 2021

Published18 Jan 2021

Abstract

Background. To investigate the effects of phenylethanoid glycosides (PhGs) extracted from Herba Cistanches on the behavioral and cognition capacity of the APP/PSI transgenic mice with Alzheimer’s disease (AD). Methods. AD mice were randomly divided into the control group, model group, donepezil group, PhG groups, and verbascose group, respectively. Three weeks later, the animals were subject to behavioral and cognition evaluation by the nesting test, Morris water maze test, and step-down test. Results. The cognition capacity in these groups showed a significant increase compared with that in the model group. The step-down test indicated that the errors induced by the memory decrease in the PhG groups and verbascose group showed a significant decrease compared with those in the model group (). Conclusions. PhGs attenuated the cognitive dysfunction features of the APP/PSI transgenic gene. Besides, PhGs were the active components for the anti-AD activity of H. Cistanches.

1. Background

Alzheimer’s disease (AD) is an age-related degenerative disease of the central nervous system (CNS) featured by progressive cognitive dysfunction and memory impairment [1–3]. With the aging process and extension of life span worldwide, the prevalence of AD is on an increasing trend, which results in high morbidity, long disease course, and high treatment expenditure. To date, the mechanism of AD is still not well defined [4–7]. Therefore, it is urgent to investigate the mechanism of AD and develop an effective method for the prevention, control, and treatment of AD accordingly.

To date, there is still no effective method for the prevention and treatment of AD, and most of the agents used in clinical settings are used for symptomatic treatment. The approved agents for AD by FDA include cholinesterase inhibitors (e.g., donepezil) and excitatory amino acid receptors (e.g., memantine) that are considered to attenuate the symptoms and improve the cognitive/behavioral capacities. Nevertheless, efficiency is not satisfactory due to limited treatment responses after administration [8–10]. Traditional Chinese medicine, with a long history, based on thousands of years of experience, shows extensive sources and several advantages compared to the chemical agents, including multiple targets, excellent safety, few side events, and suitability for long-term administration. These herbal medicines present superiority to other agents in terms of treating chronic and refractory diseases. Additionally, great potency was reported in these agents in the treatment of AD [11–13]. Therefore, increasing efforts have been made on the development of new agents for AD from herbal medicines based on modern techniques.

Herba Cistanches, known as Rou Cong-Rong in Chinese, are an endangered wild species that are mainly distributed in the arid lands and warm deserts of northwestern China. Herba Cistanche is applied as a tonic and/or in a formula for chronic renal disease, impotence, and senile constipation with a history of two thousand years. The chemical constituents of Herba Cistanche mainly consist of volatile oils, nonvolatile phenylethanoid glycosides (PhGs), iridoids, lignans, alditols, oligosaccharides, and polysaccharides. There have been an increasing number of studies focusing on antiaging, especially the animal models established using Aβ25-35, D-galactose, Al₂O₃, quinolinic acid, and scopolamine. These studies indicated that the PhGs could contribute to memory, attenuation of oxidative stress in brain tissues, inhibition of nerve cell apoptosis, and decline of acetylcholine esterase [14–16].

In the ancient prescriptions, H. Cistanche is frequently for nurturing the kidney and inhibiting the aging process. In modern times, the herb has been approved to be effective for treating certain diseases with satisfactory safety. Besides, it has been utilized in individuals living in Mainland China [17]. In 2016, the CFSA approved the safety of H. Cistanche in food sources, and then, in 2018, the National Health Commission of the PRC issued that it could serve as a food source and a candidate for the research and development of new drugs [18, 19]. To our best knowledge, the active components of H. Cistanche are PhGs, among which echinacoside and verbascose serving as the most representative components have been listed as a quality index for H. Cistanche by the Chinese Pharmacopoeia. For instance, the PhGs of H. Cistanche may serve as a food additive after purification.

Our previous studies indicated that the PhG extracted from the H. Cistanche was far more than 80% [11]. Besides, the PhG monomer and the verbascose were high in content and served as the major active components. Extensive studies indicated that the total PhGs and PhG monomer (e.g., verbascose and echinacoside) presented significant anti-AD efficiency. For example, animal studies showed that total PhGs, verbascose, and echinacoside could significantly contribute to the increase of the learning/memorizing capacity and cognitive behaviors, downregulate the oxidative stress in brain tissues, inhibit the apoptosis of nerve cells, and decrease the generation of Aβ in brains and the acetylcholine esterase activity [20–25]. In vitro experiments revealed that PhGs could act on the AD cellular model, bring down the oxidative stress, remove the free radical, inhibit the amyloid-β aggregation, and decrease the neuron loss and nerve cell apoptosis [20, 25, 26]. Furthermore, PhGs could attenuate the cognitive dysfunction and the generation of Aβ1-40 and Aβ1-42 in the hippocampus in the APPswe/PSIdE9 transgenic mice. It can regulate the upstream and downstream targets of the insulin signaling pathway, which then improved the signal transmission of the insulin and regulated the brain energy metabolism, as well as the subsequent anti-AD capacity [27].

Animal models are crucial for disease-related research studies and pharmacy development. The AD model based on transgenic animals has been considered one of the most important advances as the transgenic AD animal model could mimic AD at a molecular level, which presented typical symptoms and signs. Besides, this model is superior to the other AD-related models in stability and reliability. Up to now, no transgenic AD model has been conducted to investigate the effects of the PhG monomer on the pathogenesis of AD. In this study, the APP/PSI AD mice model was established, followed by the determination of anti-AD activities of a PhG monomer termed as verbascose by evaluating the nesting test, Morris water maze test, and step-down test.

2. Methods

2.1. Agent

The PhGs of H. Cistanche were prepared according to our conventional description [20]. The quality determined using the UV method was up to 87.6%. The echinacoside and verbascose content determined by HPLC was 37.8% and 17.7%, respectively. The graphic formula for PhGs, verbascose, and echinacoside is shown in Figure 1. Stems of C. tubulosa (Schrenk) Wight were collected in October 2016 from Xinjiang, China. The plant was identified by Dr. Junping Hu. All these voucher specimens (No. 201610) have been deposited at the Plant Herbarium, School of Pharmacy, Xinjiang Medical University, Xinjiang, China.

2.2. Animals

Ten male APP/PSI transgenic mice (3 months) and twenty female mice (male: 10; female: 10, 20-30 g) were purchased from the Model Animal Research Center of Nanjing University (SCXK 2015-0001, Nanjing, China). The animals were fed in the specific pathogen-free (SPF) chambers in the Animal Center of Xinjiang Medical University (SCXK 2011-0001, Xinjiang, China) on a SPF-grade diet. All the animals have free access to food and sterilized water. The study protocols were approved by the Ethics Committee of Xinjiang Medical University.

2.3. Proliferation and Identification of APP/PSI Transgenic Mice

The newborn transgenic mice (2-3 weeks) were subject to tail cutting with a length of 0.5 cm for DNA extraction. The tail was placed in an Eppendorf tube, followed by adding prolease K until a concentration of 400 μg/ml. Subsequently, the mixture was vortexed at 55°C overnight and then was centrifuged at 13,000 rpm for 10 min at 4°C to obtain the supernatant. DNA extraction was performed using a commercial kit according to the manufacturer’s instructions (Qiagen, Germany).

For the DNA amplification, specific primers for APP and PSI were designed as mentioned in Table 1. The amplification was conducted in a total volume of 20 μl using the following conditions: 94°C predenaturation for 5 min, followed by 35 cycles of denaturation at 94°C for 30 sec, 65°C for 35 sec, and 72°C for 45 sec, as well as 72°C for 3 min. The produced DNA products were subject to agarose gel electrophoresis at a constant voltage of 100 V for 30 min. Finally, the images were visualized using a ChemiDoc MP system.

2.4. Grouping

Using the randomization generated by SPSS 18.0 software, the AD mice were randomly divided into the (i) control group (, C57BL/6J mice); (ii) model group (); (iii) donepezil group (, 0.65 mg/kg, intragastric administration); (iv) PhG groups subject to PhG via lavage with a concentration of 250 mg/kg (), 125 mg/kg (), and 62.5 mg/kg (); and (v) verbascose group (, 125 mg/kg, intragastric administration). Animals used in groups (ii)-(v) were APPswe/PSIdE9 transgenic mice. The lavage was performed at the age of 6 months and lasted for 3 months with a frequency of once per day. Animals in the control and model groups were subject to injection of double distilled water intragastric administration.

2.5. Nesting Test

The animals were fed separately for at least 24 h before the test in a standard cage (), filled with sterilized wood shavings with a thickness of 1 cm. Initially, the latency time was monitored at the beginning of the test, and a total time of 120 was obtained. The nesting score was calculated as previously described [28].

2.6. Morris Water Maze Test

The apparatus consisted of a circular pool filled with water ( and 40 cm in depth) located in a test room with white walls and several cues on them. A platform (10 cm in diameter) was immersed 1 cm under the surface of the water in one of the four identical quadrants. The location of the platform was fixed throughout the acquisition trials, during which mice were individually placed in the water facing the wall of the pool in order to negate any directional influence. On days 1 and 2, the acquisition trial test was conducted including 4 sessions per day for 6 consecutive days. For each session, the mice were allowed to escape by swimming to the invisible platform and the escape latency (i.e., the time required to locate and climb onto the platform) and swimming speed were recorded with the cutoff time 60 s. Mice that fail to find the platform within 60 s were guided to the platform manually and allowed to stay on it for 10 s. On day 11, the acquisition trial test was performed again for the last 6 consecutive days after all the drug treatments.

2.7. Step-Down Test

About 24 h after the last drug medication, the animals were required to be in the step-down facility and adaptive environment for 3 min. The time was set for 5 min, and the voltage was 32 V. Upon stimulation, the mice tried to jump onto the platform and then were timed in the presence of infrared detector signal changes. The latency time was recorded as the time from the platform to the slot bottom for the first time. In cases of not jumping off the platform, the latency time was recorded as 5 min. Then, the total stimulation frequency was recorded after the latency stage. The test was accomplished in 2 days. Learning and memory were observed on day 1 and day 2, respectively. The latency stage and error frequency were recorded for each mouse.

2.8. Statistical Analysis

SPSS 18.0 software was used for the statistical analysis. Data were presented as . Student’s -test was performed for the intergroup comparison. was considered to be statistically significant.

3. Results

3.1. Genotype Identification

Given the fact that genome DNA served as the template for amplification, two bands with a length of 344 kb and 608 kb were obtained in the F1 generation, respectively. This was consistent with the length of the APP gene and PSI gene (Figure 2).

3.2. Nesting Score

Five grades were divided into the nesting score (Figure 3). In the control group, nesting behavior was observed within a few minutes after placing the papers into the cage. In the model group, the exploration of the mice was comparatively decreased, and some animals may even present anxiety-related behaviors such as grooming and face washing, which triggered a delay in nesting behavior. Most of these animals showed a score of 1 or 2. Nevertheless, a significant increase was noticed in the nesting score, which presented in a time-dependent manner after PhG treatment (Figure 4).

(a)

(b)

(c)

(d)

(e)

(a)

(b)

(c)

(d)

3.3. Effects of PhGs on Navigating Transgenic AD Mice in the Latency Stage

With the extension of drill time, the latency time in each group showed a significant decrease. The first 2 days served as drill time. On day 3, the latency time in the model group showed significant extension compared with that in the normal control (). Similarly, on days 4 and 5, the latency time in the model group showed significant extension compared with that in the normal control (). On day 3, the latency time in the donepezil group showed a significant decrease compared with that in the model group (). The latency time in the PhG groups showed a significant decrease in a dose-dependent manner compared with that in the model group (, Table 2).

3.4. PhGs Significantly Attenuated the Swimming Trace of Transgenic AD Mice

In the model group, the swimming trace of the mice was in a typical manner of marginal searching. In the PhG groups and verbascose group, the swimming trace was in a linear type or tendency type. This indicated that PhG could significantly improve the special memory of APP/PSI transgenic AD mice (Figure 5).

(a)

(b)

(c)

(d)

(e)

(f)

(g)

3.5. Effects of PhGs on Special Exploration of AD Mice

The platform was retrieved on day 6 of the water maze test to investigate the special exploration capacity. The frequency of passing through the platform was recorded within 60 sec. Our data showed that a significant decrease was noticed in the frequency of passing through the platform in the model group, compared with the normal control (). Compared with the model group, a significant increase was noticed in the frequency of passing through the platform in the PhG groups and verbascose group (, Table 3).

As the platform was placed on the third quadrant, it was termed as the objective quadrant. Longer retention in the quadrant implied significant improvement in the learning and memory of the mice after the administration of agents. Our data showed that there was a significant decrease in the retention in the objective quadrant in the model group compared with the normal control (). Compared with the model group, a significant increase was noticed in the retention in the PhG groups, donepezil group, and verbascose group, respectively (, Table 4).

3.6. Effects of PhGs on the Step-Down Test in Transgenic AD Mice

The latency time in the model group was significantly lower than that in the control group (). In addition, donepezil could induce a significant increase in the latency time (). Similarly, the PhG groups and verbascose group also showed significantly longer latency time (). Moreover, the PhG groups and verbascose group showed a significant decrease in the error frequency in the step-down test induced by memory and learning impairment (). These indicated that PhGs contributed to the improvement of memory and learning capacity of transgenic AD mice (Table 5).

4. Discussion

AD is a degenerative nervous system disease that frequently occurs in the aged population. Unfortunately, the exact mechanism is still not well defined, which limits drug screening to some extent. To date, extensive studies have been conducted on drug development in view of animal research, and several AD animal models are available including models based on Aβ25-35, D-galactose, Al₂O₃, quinolinic acid, and scopolamine. These models trigger cognitive dysfunction, but they present disadvantages including the late onset of disease, large individual differences, and longer experimental duration that hampered mimicking the progressive and degenerative lesions [29–31]. With the advances of the transgenic technique in establishing AD animal models [27, 32, 33], great strides have been made in understanding the pathogenesis of AD together with the development of new drugs. Nevertheless, the pathogenesis of AD is rather complex, and only a few gene targets responsible for the onset of AD have been identified [34–36]. On this basis, the transgenic AD model deserves further application in drug development. Identification of gene sites associated with AD based on the transgenic AD model using the crossbreeding technique will contribute to the treatment of AD in clinical settings and establishing new AD models involving multiple virulence genes.

In this study, the selected APPswe/PSIdE9 model contributed significantly to APP metabolism, development, and pathogenesis of AD, as well as disease progression. For the proliferation and identification of transgenic mice, we extracted DNA from the blood samples and tissues, respectively. For the blood sample collection, in order to ensure the survival of animals, the sample was collected from the tail top, which was difficult to perform with less sample volume. Besides, it may induce injury to the animals and affect the subsequent analysis. In contrast, DNA extraction from tissues was usually performed at weeks 6-8, which was easy to perform and caused less injury to the growth of animals. Furthermore, there were no statistical differences in the DNA content and purity between these two methods. Therefore, DNA was extracted from the tissues for the identification of the genome of transgenic mice.

The typical clinical manifestations for AD are a progressive decrease in learning and memory. Thus, observation of learning and memory is crucial for the evaluation of drug efficiency. In this study, the nesting test was utilized together with the Morris water maze test and step-down test to investigate the effects of PhGs on the memory and learning of APP/PSI transgenic mice. In the navigation test, the latency time in the model group indicated a significant increase compared with that in the normal control (). Meanwhile, a significant decrease was noticed in the latency time in the donepezil group compared with the model group (). Compared with the model group, the latency time in the PhG groups showed a significant decrease in a dose-dependent manner (). In the special exploration, a significant decrease was noticed in the frequency of passing through the platform in the model group compared with the normal control (). Compared with the model group, the frequency of passing through the platform in the PhG groups and donepezil group showed a significant increase (). In the step-down test, the frequency of error in jumping induced by memory and learning impairment was significantly decreased after administration of PhGs (). The behavioral test revealed that PhG interference could significantly improve the memory and learning of the APP/PSI transgenic AD mice.

Traditional herbal medicine, with a long history, has been commonly utilized in treating chronic disease and refractory disorders. Currently, the development of new drugs on AD based on herbal medicine has been highly focused on the extraction of active components and/or compound preparation. Compared with the active extraction component, the single monomer component shows various advantages such as the utilization of low concentration, easy investigation of target sites, and better efficiency direction. Verbascose is a representative monomer of PhGs as it shows high content and activity. In this study, the verbascose group showed better anti-AD capacity compared with the PhG groups. This supports the research and development of anti-AD agents based on verbascose. The H. Cistanches show a long history in food utilization, dating back to the Han dynasty. Modern techniques approve that H. Cistanches are safe as food. In this study, we approved the potency of H. Cistanches in the fields of functional food, drug development, and health care, especially in the aged population and the fatigue individuals.

The animal model is crucial for research studies on disease and drug development. Recently, the transgenic technique has been used to establish the AD model, which can mimic the pathogenesis of AD at molecular levels, together with the typical symptoms and vital signs. These models have been proved to be effective in stability and reliability compared with the other AD models. In this study, the APP/PSI transgenic mice model that is well acknowledged for mimicking the pathological processes of AD is utilized, which presented features of behavioral dysfunction, cognitive disorder, senile plaques, neurofibrillary tangles, and neuronic death [37–39]. In this study, we firstly utilized transgenic AD mice to investigate the effects of PhGs on learning and memory, which can provide helpful information for the research and development of anti-AD agents based on PhGs.

In summary, PhGs could attenuate the cognitive dysfunction features of the APP/PSI transgenic gene. Our study confirmed that PhGs were the active components for the anti-AD activity of H. Cistanches. It may pave the way for the development of new drugs for the treatment of AD.

Abbreviations

PhGs:	Phenylethanoid glycosides
AD:	Alzheimer’s disease
CNS:	Central nervous system.

Data Availability

All the data were available upon appropriate request.

Ethical Approval

The study protocols were approved by the Ethics Committee of Xinjiang Medical University.

Conflicts of Interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

Authors’ Contributions

YJH wrote the manuscript; HJP revised the manuscript; JBW and YJH did the data analysis and the data collection. Jianhua Yang and Bowei Ju equally contributed to this work.

Acknowledgments

This research was supported by the Xinjiang Key Laboratory of Natural Drug Active Components and Drug Release Technology (XJDX1713), the National Natural Science Foundation of China (Nos. 81860735 and 81560629), and the reserve candidate project for the leader of scientific and technological innovation in Xinjiang Uygur Autonomous Region (2019XS14).

References

C. A. Lane, J. Hardy, and J. M. Schott, “Alzheimer's disease,” European Journal of Neurology, vol. 25, no. 1, pp. 59–70, 2018.
View at: Publisher Site | Google Scholar
S. Jantarasaengaram, C. Suthipintawong, S. Kanchanawat, and K. Thanagumtorn, “Ruptured vasa previa in velamentous cord insertion placenta,” Journal of Perinatology, vol. 27, no. 7, pp. 457–459, 2007.
View at: Publisher Site | Google Scholar
M. P. Murphy, “Amyloid-beta solubility in the treatment of Alzheimer's disease,” The New England Journal of Medicine, vol. 378, no. 4, pp. 391-392, 2018.
View at: Publisher Site | Google Scholar
R. J. Castellani, R. K. Rolston, and M. A. Smith, “Alzheimer disease,” Disease-a-Month, vol. 56, no. 9, pp. 484–546, 2010.
View at: Publisher Site | Google Scholar
B. P. Morgan, “Complement in the pathogenesis of Alzheimer's disease,” Seminars in Immunopathology, vol. 40, no. 1, pp. 113–124, 2018.
View at: Publisher Site | Google Scholar
J. Jia, F. Wang, C. Wei et al., “The prevalence of dementia in urban and rural areas of China,” Alzheimers Dement, vol. 10, no. 1, pp. 1–9, 2014.
View at: Publisher Site | Google Scholar
B. Silver, K. Ramaiya, S. B. Andrew et al., “EADSG guidelines: insulin therapy in diabetes,” Diabetes Therapy, vol. 9, no. 2, pp. 449–492, 2018.
View at: Publisher Site | Google Scholar
Q. Liu, S. C. Wang, and K. Ding, “Research advances in the treatment of Alzheimer's disease with polysaccharides from traditional Chinese medicine,” Chinese Journal of Natural Medicines, vol. 15, no. 9, pp. 641–652, 2017.
View at: Publisher Site | Google Scholar
R. F. Melanie-Jayne, R. Howes, and P. J. Houghton, “Chapter two-effect of Chinese herbal medicine on Alzheimer's disease,” International Review of Neurobiology, vol. 135, pp. 29–56, 2017.
View at: Publisher Site | Google Scholar
J. Mao, S. Huang, S. Liu et al., “A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation,” Aging Cell, vol. 14, no. 5, pp. 784–796, 2015.
View at: Publisher Site | Google Scholar
L. Hao, X. Lu, M. Sun, K. Li, L. Shen, and T. Wu, “Protective effects of L-arabinose in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats,” Food & Nutrition Research, vol. 59, no. 1, article 28886, 2015.
View at: Publisher Site | Google Scholar
B. Klimova and K. Kuca, “Alzheimer's disease and Chinese medicine as a useful alternative intervention tool: a mini-review,” Current Alzheimer Research, vol. 14, no. 6, pp. 680–685, 2017.
View at: Publisher Site | Google Scholar
Y. Jiang, H. Gao, and G. Turdu, “Traditional Chinese medicinal herbs as potential AChE inhibitors for anti-Alzheimer's disease: a review,” Bioorganic Chemistry, vol. 75, pp. 50–61, 2017.
View at: Publisher Site | Google Scholar
X. Y. Cheng, T. Wei, B. Guo, W. Ni, and C.-Z. Liu, “Cistanche deserticola cell suspension cultures: Phenylethanoid glycosides biosynthesis and antioxidant activity,” Process Biochemistry, vol. 40, no. 9, pp. 3119–3124, 2005.
View at: Publisher Site | Google Scholar
O. A. Snytnikova, Y. P. Tsentalovich, N. A. Stefanova et al., “The therapeutic effect of mitochondria-targeted antioxidant SkQ1 and Cistanche deserticola is associated with increased levels of tryptophan and kynurenine in the rat lens,” Doklady. Biochemistry and Biophysics, vol. 447, no. 1, pp. 300–303, 2012.
View at: Publisher Site | Google Scholar
H. S. Wong and K. M. Ko, “Herba Cistanches stimulates cellular glutathione redox cycling by reactive oxygen species generated from mitochondrial respiration in H9c2 cardiomyocytes,” Pharmaceutical Biology, vol. 51, no. 1, pp. 64–73, 2013.
View at: Publisher Site | Google Scholar
R. X. Fang Peng, C. Xu, Y. Qi, Y. Shi, Z. Ye, and J. Chen, “Textual research on the medicinal and diet therapy of Cistanche deserticola,” Chinese Journal of Pharmacy, vol. 52, no. 5, 2017.
View at: Google Scholar
K. Zhang, H. Shi, H. Xi et al., “Genome-wide lncRNA microarray profiling identifies novel circulating lncRNAs for detection of gastric cancer,” Theranostics, vol. 7, pp. 213–227, 2017.
View at: Publisher Site | Google Scholar
Y.-S. Tong, X.-W. Wang, X.-L. Zhou et al., “Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma,” Molecular Cancer, vol. 14, no. 1, p. 3, 2015.
View at: Publisher Site | Google Scholar
J. Yang, B. Ju, Y. Yan et al., “Neuroprotective effects of phenylethanoid glycosides in an in vitro model of Alzheimer's disease,” Experimental and Therapeutic Medicine, vol. 13, no. 5, pp. 2423–2428, 2017.
View at: Publisher Site | Google Scholar
J. X. Jia, X. S. Yan, Z. P. Cai et al., “The effects of phenylethanoid glycosides, derived from Herba Cistanche, on cognitive deficits and antioxidant activities in male SAMP8 mice,” Journal of Toxicology and Environmental Health. Part A, vol. 80, no. 22, pp. 1180–1186, 2017.
View at: Publisher Site | Google Scholar
X. M. Peng, L. Gao, S. X. Huo, X. M. Liu, and M. Yan, “The mechanism of memory enhancement of acteoside (verbascoside) in the senescent mouse model induced by a combination of D-gal and AlCl3,” Phytotherapy Research, vol. 29, no. 8, pp. 1137–1144, 2015.
View at: Publisher Site | Google Scholar
J. Chen, S. N. Zhou, Y. M. Zhang, Y. L. Feng, and S. Wang, “Glycosides of Cistanche improve learning and memory in the rat model of vascular dementia,” European Review for Medical and Pharmacological Sciences, vol. 19, no. 7, pp. 1234–1240, 2015.
View at: Google Scholar
A. Nagakura, Y. Shitaka, J. Yarimizu, and N. Matsuoka, “Characterization of cognitive deficits in a transgenic mouse model of Alzheimer's disease and effects of donepezil and memantine,” European Journal of Pharmacology, vol. 703, no. 1-3, pp. 53–61, 2013.
View at: Publisher Site | Google Scholar
C. R. Wu, H. C. Lin, and M. H. Su, “Reversal by aqueous extracts of Cistanche tubulosa from behavioral deficits in Alzheimer's disease-like rat model: relevance for amyloid deposition and central neurotransmitter function,” BMC Complementary and Alternative Medicine, vol. 14, no. 1, p. 202, 2014.
View at: Publisher Site | Google Scholar
M. Kurisu, Y. Miyamae, K. Murakami et al., “Inhibition of amyloid β aggregation by acteoside, a phenylethanoid glycoside,” Bioscience, Biotechnology, and Biochemistry, vol. 77, no. 6, pp. 1329–1332, 2013.
View at: Publisher Site | Google Scholar
T. J. Revett, G. B. Baker, J. Jhamandas, and S. Kar, “Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology,” Journal of Psychiatry & Neuroscience, vol. 38, no. 1, pp. 6–23, 2013.
View at: Publisher Site | Google Scholar
B. N. Gaskill, A. Z. Karas, J. P. Garner, and K. R. Pritchett-Corning, “Nest building as an indicator of health and welfare in laboratory mice,” Journal of Visualized Experiments, vol. 82, no. 82, article 51012, 2013.
View at: Publisher Site | Google Scholar
A. Prakash, B. Medhi, and K. Chopra, “Granulocyte colony stimulating factor (GCSF) improves memory and neurobehavior in an amyloid-β induced experimental model of Alzheimer's disease,” Pharmacology, Biochemistry, and Behavior, vol. 110, pp. 46–57, 2013.
View at: Publisher Site | Google Scholar
E. Kuznetsova and R. Schliebs, “β-Amyloid, cholinergic transmission, and cerebrovascular system - a developmental study in a mouse model of Alzheimer's disease,” Current Pharmaceutical Design, vol. 19, no. 38, pp. 6749–6765, 2013.
View at: Publisher Site | Google Scholar
T. A. Masoodi, S. A. Al Shammari, M. N. Al-Muammar, A. A. Alhamdan, and V. R. Talluri, “Exploration of deleterious single nucleotide polymorphisms in late-onset Alzheimer disease susceptibility genes,” Gene, vol. 512, no. 2, pp. 429–437, 2013.
View at: Publisher Site | Google Scholar
M. Nizzari, S. Thellung, A. Corsaro et al., “Neurodegeneration in Alzheimer disease: role of amyloid precursor protein and presenilin 1 intracellular signaling,” Journal of Toxicology, vol. 2012, Article ID 187297, 13 pages, 2012.
View at: Publisher Site | Google Scholar
H. Zheng, Q. Zhou, Y. Du et al., “The hypothalamus as the primary brain region of metabolic abnormalities in APP/PS1 transgenic mouse model of Alzheimer's disease,” Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol. 1864, no. 1, pp. 263–273, 2018.
View at: Publisher Site | Google Scholar
J. Zhang, Y. Guo, Y. Wang, L. Song, R. Zhang, and Y. Du, “Long-term treadmill exercise attenuates Aβ burdens and astrocyte activation in APP/PS1 mouse model of Alzheimer's disease,” Neuroscience Letters, vol. 666, pp. 70–77, 2018.
View at: Publisher Site | Google Scholar
K. Krajnak and R. Dahl, “A new target for Alzheimer's disease: a small molecule SERCA activator is neuroprotective in vitro and improves memory and cognition in APP/PS1 mice,” Bioorganic & Medicinal Chemistry Letters, vol. 28, no. 9, pp. 1591–1594, 2018.
View at: Publisher Site | Google Scholar
S. M. Raefsky, R. Furman, G. Milne et al., “Deuterated polyunsaturated fatty acids reduce brain lipid peroxidation and hippocampal amyloid β-peptide levels, without discernable behavioral effects in an APP/PS1 mutant transgenic mouse model of Alzheimer's disease,” Neurobiology of Aging, vol. 66, pp. 165–176, 2018.
View at: Publisher Site | Google Scholar
B. Liu, J. L. Frost, J. Sun et al., “MER5101, a novel Aβ1-15:DT conjugate vaccine, generates a robust anti-Aβ antibody response and attenuates Aβ pathology and cognitive deficits in APPswe/PS1ΔE9 transgenic mice,” The Journal of Neuroscience, vol. 33, no. 16, pp. 7027–7037, 2013.
View at: Publisher Site | Google Scholar
D. Cheng, W. Logge, J. K. Low, B. Garner, and T. Karl, “Novel behavioural characteristics of the APPSwe/PS1ΔE9 transgenic mouse model of Alzheimer's disease,” Behavioural Brain Research, vol. 245, pp. 120–127, 2013.
View at: Publisher Site | Google Scholar
Y. Liu, C. L. Hettinger, D. Zhang, K. Rezvani, X. Wang, and H. Wang, “The proteasome function reporter GFPu accumulates in young brains of the APPswe/PS1dE9 Alzheimer's disease mouse model,” Cellular and Molecular Neurobiology, vol. 34, no. 3, pp. 315–322, 2014.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2021 Jianhua Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies