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
Open accessAbstract
BACKGROUND: Cistanche tubulosa (Schenk) R. Wight (CT) is commonly used to treat forgetfulness by traditional Chinese physicians. This study presents the ameliorating effects of CT extract which was quantified with three phenylpropanoid glycosides in Alzheimer's disease (AD)-like rat model. METHODS: Amyloid β peptide 1-42 (Aβ 1-42) intracisternally infused to rats by osmotic pump (Alzet 2002) was used as an AD-like rat model. The major pathological makers were measured including Aβ 1-42 immunohistochemical stain, behavioral tests (inhibitory avoidance task and Morris water maze) and central neurotransmitter functions. RESULTS: Aβ 1-42 caused the cognitive deficits, the increase in the amyloid deposition and acetylcholinesterase activities, and the decrease in the levels of brain's acetylcholine and dopamine. Daily administration of CT extract throughout Aβ 1-42 infusion periods ameliorated the cognitive deficits, decreased amyloid deposition and reversed cholinergic and hippocampal dopaminergic dysfunction caused by Aβ 1-42. Donepezil also ameliorated the cognitive dysfunction, but only blocked the amyloid deposition and cholinergic dysfunction caused by Aβ 1-42. CONCLUSIONS: We suggest that CT extract, containing enough echinacoside and acteoside, ameliorated the cognitive dysfunction caused by Aβ 1-42 via blocking amyloid deposition, reversing cholinergic and hippocampal dopaminergic neuronal function.
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Cistanche tubulosa aqueous extract (100-200 mg/kg) improved cognitive function, reduced amyloid deposition, and reversed cholinergic and dopaminergic dysfunction, with 200 mg/kg significantly decreasing cortical AChE activity in amyloid beta-infused rats.
“Cistanche tubulosa aqueous extract (100–200 mg/kg) improved cognitive function, reduced amyloid deposition, and reversed cholinergic and dopaminergic dysfunction, with the 200 mg/kg dose significantly decreasing cortical AChE activity in Aβ-infused rats [80].”
From Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review (2025) · cites this paper as [80]
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Self-citationStudies on Cistanches Herba: A Bibliometric Analysis
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“Echinacoside has a wide range of neuropharmacological activities and is considered as a potential natural active ingredient with a broad spectrum and multi-target effect in the treatment of Alzheimer’s disease [20,39,95,96].”
BackgroundYuan, P., Fu, C., Yi, Y., Aipire, A., Zhou, F., Wei, X., Wang, W., Lv, J., Li, Y., Xia, L., et al. (2021) · Integrative Cancer Therapies · doi:10.1177/15347354211013085 · Cited by 21 · see citing works
“Cistanche is a TCM including phenylethanoid glycosides (PhGs), iridoids, lignin and polysaccharides which has various biological functions, such as anti-oxidation, anti-in ammation, anti-aging, memory enhancement and immune enhancement functions [9].”
BackgroundZhang, X., Li, L., Chen, T., Sun, Z.-Y., Tang, W., Wang, S., Wang, T., Wang, Y., & Zhang, H. (2018) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2018/4642018 · Cited by 20 · see citing works
“Furthermore, CT extract (200mg/kg) was observed to reduce ACHE andMAO-A cortical activity in the model group after 15 days treatment [72].”
MethodZhang, W., Huo, S., Wen, Y., Xing, H., Zhang, Q., Li, N., Zhao, D., Sun, X., Jie, X. U., Ming, Y. A. N., et al. (2015) · Chinese Journal of Natural Medicines · doi:10.1016/s1875-5364(15)30060-1 · Cited by 19 · see citing works
Zhou, X., Xu, M.-B., Jin, T.-Y., Rong, P.-Q., Zheng, G., & Lin, Y. (2019) · Aging and Disease · doi:10.14336/ad.2018.0815-1 · Cited by 19 · see citing works
“The open field test was conducted in 2 studies [33, 49] that both clearly showed ECC increased the frequency of visits and time spent in the hole compared with controls (P<0.”
BackgroundMethodResultInfluentialAbudujilile, D., Wang, W., Aimaier, A., Chang, L., Dong, Y., Wang, Y., Fan, X., Ma, Y., Wang, Y., Ziyayiding, D., et al. (2022) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-022-03743-6 · Cited by 17 · see citing works
Lin, W., Yao, C., Cheng, J., Kao, S.-T., Tsai, F., & Liu, H.-P. (2017) · Phytomedicine · doi:10.1016/j.phymed.2017.01.006 · Cited by 16 · see citing works
Guo, Y., Cui, Q., Ren, S., Hao, D., Morikawa, T., Wang, D., Liu, X., & Pan, Y. (2021) · Journal of Natural Medicines · doi:10.1007/s11418-021-01508-y · Cited by 15 · see citing works
“Modern pharmacological researches displayed that Cistanches Herba has multiple bioactivities, such as neuroprotection [9], anti-inflammatory [10], anti-tumor activities [11], hepatoprotective activity [12], anti-osteoporosis activity [13, 14], antifatigue activity [15], etc.”
BackgroundLaeken, N. V., Pauwelyn, G., Dockx, R., Descamps, B., Brans, B. T., Peremans, K. Y., Baeken, C., Goethals, I., Vanhove, C., & Vos, F. D. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1899-8 · Cited by 14 · see citing works
Yang, D., Li, J., Liang, C., Tian, L., Shi, C., Hui, N., Liu, Y., Ling, M., Xin, L., Wan, M., et al. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153770 · Cited by 14 · see citing works
Fu, C., Li, J., Aipire, A., Xia, L., Yi, Y., Chen, Q., Lv, J., Wang, X., & Li, J. (2018) · Oncology Letters · doi:10.3892/ol.2018.9635 · Cited by 14 · see citing works
“Cistanche is a type of CHM and exerts various biological functions, including anti‑oxidation, anti‑inflammation and neuroprotection (22,23).”
Auger, F., Martin, F., Pétrault, O., Samaillie, J., Hennebelle, T., Trabelsi, M.-S., Bailleul, F., Staels, B., Bordet, R., & Duriez, P. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0133-y · Cited by 13 · see citing works
Pharmacological intervention for chronic phase of spinal cord injury
Tohda, C. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00176 · Cited by 12 · see citing works
Age related neurodegenerative Alzheimer’s disease: Usage of traditional herbs in therapeutics
Singh, A., Agarwal, S., & Singh, S. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134679 · Cited by 11 · see citing works
Lu, C.-W., Huang, S.-K., Lin, T.-Y., & Wang, S.-J. (2018) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.2018.22.3.249 · Cited by 10 · see citing works
“Echinacoside enters the brain and produces numerous beneficial effects, including neuroprotection and cognition improvement [10-12].”
BackgroundYang, J., Ju, B., & Hu, J. (2021) · BioMed Research International · doi:10.1155/2021/1291549 · Cited by 11 · see citing works
“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].”
BackgroundInhibition of Amyloid Beta Aggregation and Deposition of Cistanche tubulosa Aqueous Extract
Chao, C.-L., Huang, H.-W., Huang, H., Chao, H.-F., Yu, S.-W., Su, M., Wang, C.-J., & Lin, H. (2019) · Molecules · doi:10.3390/molecules24040687 · Cited by 10 · see citing works
“According to our previous studies [18,19,24,25], CTE displayed potential anti-dementia activity.”
BackgroundMethodResultInfluentialSelf-citationHerbal biomolecules acting on central nervous system
Otimenyin, S. O. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-85852-6.00030-5 · Cited by 10 · see citing works
Guo, Y., Wang, L., Li, Q., Zhao, C., He, P., & Ma, X. (2019) · Journal of Medicinal Food · doi:10.1089/jmf.2018.4354 · Cited by 9 · see citing works
“34,35 Moskovtsev et al. found negative correlations between sperm DNA damage and sperm density, activity, and morphology.”
Cui, Q., Pan, Y., Yan, X., Qu, B., Liu, X., & Xiao, W. (2016) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.7795 · Cited by 8 · see citing works
Chen, L., Liu, X., Zheng, J., Li, G., Yang, B., He, A., Liu, H., Liang, Y., Wang, W. A., & Du, J. C. (2024) · Phytotherapy Research · doi:10.1002/ptr.8275 · Cited by 7 · see citing works
“…activity, suggesting that the memory-improving effects of Cistanche might be related to decrease A β deposition and neurotoxicity, which lead to a reversal of negative changes in cortical and hippocampal cholinergic function (Wu et al., 2014). towards cerebral injury and AD (Feng et al., 2019).”
Phytochemical and Pharmacological Overview ofCistancheSpecies
Lv, H., Zeng, K., Song, Y., Jiang, Y., & Tu, P. (2016) · doi:10.1002/9781118883303.ch14 · Cited by 7 · see citing works
Elhewehy, A. A., El-Fishawy, A. M., El-Rashedy, A. A. E., Fayez, A. M., Fayed, M. A. A., & Mohsen, E. (2025) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-025-00776-9 · Cited by 6 · see citing works
Lauterbach, E. C. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.194708 · Cited by 6 · see citing works
“In rats receiving intra-cisternal Aβ42, concomitant donepezil decreased amyloid deposition, prevented cholinergic dysfunction, and improved spatial and avoidance memory (Wu et al., 2014).”
BackgroundMetal mixture-induced non-transgenic animal model of Alzheimer’s disease: Pros and cons
Ashok, A., & Kumar, N. (2023) · Pre-Clinical Research · doi:10.4081/pcr.2023.7768 · Cited by 5 · see citing works
Liu, L., Wan, W., Chen, W., Chan, Y., Shen, Q., & Li, Y. (2016) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2016/8591656 · Cited by 4 · see citing works
“[25] suggested that Cistanche tubulosa extract could ameliorate the cognitive dysfunction inAD-like rat model.”
BackgroundDeng, Y. L., Chen, C., Li, H., Wang, T., Zhang, X., Wang, X., & Pan, G. (2025) · Current Topics in Medicinal Chemistry · doi:10.2174/0115680266347052250407110353 · Cited by 3 · see citing works
Tubuloside A Induces DNA Damage and Apoptosis in Human Ovarian Cancer A2780 Cells
Türeyen, A., Zemheri‐Navruz, F., Günay, S., Erden, Y., & İnce, S. (2023) · European Journal of Therapeutics · doi:10.58600/eurjther1951 · Cited by 3 · see citing works
Nutraceutical innovation and health claims in China
Hu, C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802780-6.00019-5 · Cited by 2 · see citing works
Research Progress of Pharmacological Mechanism of Cistanche in the Treatment of Vascular Dementia
Yang, H., Hao, Z., & Miao, F. (2024) · Journal of Contemporary Medical Practice · doi:10.53469/jcmp.2024.06(09).04 · Cited by 1 · see citing works
Baker, D. H. A., Elsayed, A. A. A., El-Gohary, A. E., El-Garf, I. A., & Ibrahim, B. M. M. (2025) · Scientific Reports · doi:10.1038/s41598-025-26267-8 · Cited by 1 · see citing works
Feng, L., Tian, Y., Wang, X., Dai, R., Cai, S., Cao, Y.-J., & Yin-chu, S. (2018) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2018/3282385 · Cited by 1 · see citing works
“Glycosides extracted from HC enhances learning and memory deficits in AD model by depressing brain cells apoptosis rate, decreasing AChE activity, blocking amyloid deposition, reversing cholinergic and hippocampal dopaminergic neuronal function [57, 58].”
BackgroundTadevosyan, N. E., Galstyan, A. M., Tumanian, A. A., & Forgan, B. B. (2019) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-019-00759-3 · Cited by 1 · see citing works
The pathophysiological signaling and efficacy of medicinal herbal compounds in Alzheimer’s disease
Darabi, S., Ariaei, A., Gorgich, E. A. C., Rezaei, S., Behruzi, M., Abasian, Z., & Rustamzadeh, A. (2025) · Physiology and Pharmacology · doi:10.61186/phypha.29.1.3 · Cited by 1 · see citing works
Zhou, X., Meng-Bei, X., Ting-Yu, J., Rong, P.-Q., Guo-Qing, Z., & Yan, L. (2018) · Aging and Disease · doi:10.14336/ad.2018.015
Bhosale, S. S., Chakor, R., Lohidasan, S., Sivakkumar, S., & Sathiyanarayanan, A. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.120850
Abudujilile, D., Wang, W., Aimaier, A., Chang, L., Dong, Y., Wang, Y., Fan, X., Ma, Y., Wang, Y., Ziyayiding, D., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21332744
Abudujilile, D., Wang, W., Aimaier, A., Chang, L., Dong, Y., Wang, Y., Fan, X., Ma, Y., Wang, Y., Ziyayiding, D., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21332741
Guan, T., Dong, M., Zhu, Y., Zhang, J., Peng, W., Dong, J., & Chen, H. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.122162
- Authors
- Wu, C.-R., Lin, H.-C., & Su, M.-H.
- Affiliations
- China Medical University (TW)
- National Defense Medical Center (TW)
- Corresponding author
- Wu, Chi-Rei
- ORCID
- Wu, Chi-Rei
- Venue
- BMC Complementary and Alternative Medicine
- Published
- 2014-06-26
- Volume
- 14
- Issue
- 1
- Pages
- 202-202
- ISSN
- 1472-6882 (ISSN-L)
- PMC
- PMC4227081
- OpenAlex
- W2073653031
- Cited by
- 85
- References
- 31
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 7 · 2018: 15 · 2017: 13 · 2016: 13 · 2015: 2 · 2014: 1
- FWCI
- 20.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Complementary and Alternative Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Council
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Cistanche tubulosa, Alzheimer's disease, amyloid-beta 42, amyloid deposition, cognitive impairment, phenylpropanoid glycosides, echinacoside, verbascoside, acetylcholinesterase, acetylcholine, dopamine, cholinergic dysfunction, dopaminergic dysfunction, hippocampus, donepezil, traditional Chinese medicine, rat model
- MeSH terms
- Donepezil, Alzheimer Disease, Amyloid, Animals, Brain, Brain Chemistry, Disease Models, Animal, Exploratory Behavior, Indans, Male, Piperidines, Plant Extracts, Rats, Sprague-Dawley, Neurotransmitter Agents, Maze Learning, Cistanche, Rats
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