Effects of Chinese herbal medicine fuzhisan on aged rats
Abstract
Fuzhisan (FZS), a Chinese herbal complex prescription, has been used in the treatment of Alzheimer's disease (AD) for more than 15 years. Previous studies showed that FZS enhanced the cognitive ability in AD patients and AD model rats. FZS modulated the impaired cellular functions, and attenuated the damage caused by beta-amyloid protein, dose-dependently regulated and ameliorated the cholinergic functions of the Abeta(25-35)-induced AD-model mice. The SPECT imaging revealed that FZS improved the blood flow of the frontal and temporal lobes and the callosal gyrus in AD patients. However, little investigation of the effects of FZS on the naturally aged rats was reported. The underlying mechanism also remains to be explored. Recently we investigated the effects of the aqueous extract of FZS on the cognitive functions of the aged rats and the pharmacological basis for its therapeutic efficacy. The results showed a significant improvement made by FZS (0.3, 0.6, and 1.2 g/kg/d) for impaired cognitive functions of the aged rats. The rats manifested a shortened latency in Morris water maze test after intra-gavage administration (ig) of FZS for 30 consecutive days. The micro-positron emission tomography (microPET) using (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) as the tracer demonstrated that FZS promoted the glucose metabolism in the whole brains especially the temporal and parietal regions in the aged rats. The spectrophotometry and Western blot showed that FZS obviously increased the activity and the production of choline O-acetyltransferase (ChAT, EC 2.3.1.6) and the acetylcholine (ACh) contents in the hippocampus, thus regulated and ameliorated the impaired cholinergic functions of the aged rats. The therapeutical effects of FZS on the learning and memory of the aged rats were dose-dependent. The mechanism of action of FZS in ameliorating the memory dysfunction of the aged rats is ascribed to the reinforcement of the function of the cholinergic system and the enhancement of the glucose metabolism in the brains. The results of this study, together with a survey of the findings in the clinical treatment with FZS suggest that FZS may not merely alleviate the symptoms of the dementia, but may also augment the production of the neurotransmitter ACh and the energy supply in the brain to build up fitness of the patients. FZS may be beneficial for the treatment of Alzheimer's disease or cognitive impairment in old people.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Fuzhisan has been clinically utilized for senile dementia.
“Fuzhisan, a Chinese herbal complex comprising Anemone altaica in the Araceae family, Glycyrrhiza uralensis in the Leguminosae family, Scutellaria baicalensis in the Labiatae family, and Ginseng root in the Araliaceae family, has been clinically utilized for senile dementia [75].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [75]
In aged rats, Fuzhisan administered at 0.3, 0.6, and 1.2 g/kg/d ameliorated cognitive function.
“In an in vivo study in aged rats, Fuzhisan administered at 0.3, 0.6, and 1.2 g/kg/d ameliorated cognitive function.”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [75]
Fuzhisan elevated the production and activity of choline O-acetyltransferase and acetylcholine contents in the hippocampus.
“Western blot and spectrophotometry results demonstrate that Fuzhisan elevated the production and activity of choline O-acetyltransferase and acetylcholine contents in the hippocampus [75].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [75]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Petersen, R. C., Stevens, J. C., Ganguli, M., Tangalos, E. G., Cummings, J. L., & DeKosky, S. T. (2001) · Neurology · doi:10.1212/wnl.56.9.1133 · Cited by 2,065 · see citing works
Perry, E., Tomlinson, B. E., Blessed, G., Bergmann, K., Gibson, P., & Perry, R. H. (1978) · British medical journal · doi:10.1136/bmj.2.6150.1457 · Cited by 2,043 · see citing works
Brookmeyer, R., Gray, S. G., & Kawas, C. H. (1998) · American Journal of Public Health · doi:10.2105/ajph.88.9.1337 · Cited by 1,774 · see citing works
Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis
Whitehouse, P. J., Price, D. L., Clark, A. W., Coyle, J. T., & DeLong, M. R. (1981) · Annals of Neurology · doi:10.1002/ana.410100203 · Cited by 1,736 · see citing works
Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET
Herholz, K., Salmon, E., Perani, D., Baron, J.-C., Holthoff, V., Frölich, L., Schönknecht, P., Ito, K., Mielke, R., & Kalbe, E. (2002) · NeuroImage · doi:10.1006/nimg.2002.1208 · Cited by 832 · see citing works
Screening of selected Indian medicinal plants for acetylcholinesterase inhibitory activity
Vinutha, B., Prashanth, D., Salma, K., Sreeja, S. L., Pratiti, D., Padmaja, R. J., Radhika, S., Amit, A., Venkateshwarlu, K., & Deepak, M. (2006) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2006.06.014 · Cited by 389 · see citing works
Ertekin‐Taner, N., Graff-Radford, N., Younkin, L. H., Eckman, C. B., Baker, M., Adamson, J. L., Ronald, J., Blangero, J., Hutton, M. L., & Younkin, S. G. (2000) · Science · doi:10.1126/science.290.5500.2303 · Cited by 370 · see citing works
Longitudinal volumetric MRI change and rate of cognitive decline
Mungas, D., Harvey, D., Reed, B. R., Jagust, W. J., DeCarli, C., Beckett, L., Mack, W. J., Kramer, J. H., Weiner, M. W., Schuff, N., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000172913.88973.0d · Cited by 311 · see citing works
The neurobiology of memory changes in normal aging
Erickson, C. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00160-2 · Cited by 267 · see citing works
den Heijer, T., Geerlings, M. I., Hoebeek, F. E., Albert Hofman, D., Koudstaal, P. J., & Breteler, M. M. B. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.1.57 · Cited by 257 · see citing works
Loessner, A., Alavi, A., Lewandrowski, K., Mozley, D. P., Souder, E., & Gur, R. E. (1995) · PubMed · Cited by 221 · see citing works
Age-related neuropathology, cognitive decline, and Alzheimer's disease.
Keller, J. (2006) · Ageing Research Reviews · doi:10.1016/j.arr.2005.06.002 · Cited by 188 · see citing works
Septal networks: relevance to theta rhythm, epilepsy and Alzheimer's disease
Colom, L. V. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03630.x · Cited by 142 · see citing works
Zakzanis, K. K., Graham, S. J., & Campbell, Z. (2003) · Neuropsychology Review · doi:10.1023/a:1022318921994 · Cited by 140 · see citing works
Normal and pathological aging - findings of positron-emission-tomography
Mielke, R., Kessler, J., Szelies, B., Herholz, K., Wienhard, K., & Heiss, W. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050097 · Cited by 95 · see citing works
Shimoji, K., Ravasi, L., Schmidt, K., Soto‐Montenegro, M. L., Esaki, T., Seidel, J., Jagoda, E. M., Sokoloff, L., Green, M. V., & Eckelman, W. C. (2004) · PubMed · Cited by 94 · see citing works
Age-related changes in cerebral blood flow and glucose metabolism in conscious rhesus monkeys
Noda, A., Ohba, H., Kakiuchi, T., Futatsubashi, M., Tsukada, H., & Nishimura, S. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02558-1 · Cited by 88 · see citing works
Spectrophotometric assay for choline acetyltransferase
Chao, L., & Wolfgram, F. (1972) · Analytical Biochemistry · doi:10.1016/0003-2697(72)90401-0 · Cited by 78 · see citing works
Kou, J., Zhu, D., & Yan, Y. (2005) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2004.11.020 · Cited by 67 · see citing works
Optimizing rod window width in positron emission tomography
Jones, W. F., Digby, W. M., Luk, W. K., Casey, M. E., & Byars, L. G. (1995) · IEEE Transactions on Medical Imaging · doi:10.1109/42.387708 · Cited by 51 · see citing works
Alternative therapy of Alzheimer’s disease via supplementation with choline acetyltransferase
Fu, A. L., Li, Q., Dong, Z. H., Huang, S. J., Wang, Y. X., & Sun, M. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.05.116 · Cited by 44 · see citing works
Self-citationÖztürk, A., DeKosky, S. T., & Kamboh, M. I. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.08.024 · Cited by 41 · see citing works
VINCENT, D., Segonzac, G., & Vincent, M. (1958) · PubMed · Cited by 39 · see citing works
The urgency of research on ageing
Holliday, R. (1996) · BioEssays · doi:10.1002/bies.950180202 · Cited by 23 · see citing works
Spectrophotometric determination of choline acetyltransferase in the presence of dithiothreitol
Chao, L. (1978) · Analytical Biochemistry · doi:10.1016/0003-2697(78)90268-3 · Cited by 16 · see citing works
Fu, A. L., Huang, S. J., & Sun, M. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.07.199 · Cited by 15 · see citing works
Self-citationThe efficacy of fuzhisan in patients with Alzheimer's disease
Wang, C. (2005) · Journal of Apoplexy and Nervous Diseases · Cited by 11 · see citing works
Altered cerebral glucose metabolism in an animal model of diabetes insipidus: A micro-PET study
Idbaïh, A., Burlet, A. J., Adle‐Biassette, H., Boisgard, R., Coulon, C., Paris, S., Marie, Y., Donadieu, J., Hoang‐Xuan, K., & Ribeiro, M. J. (2007) · Brain Research · doi:10.1016/j.brainres.2007.05.016 · Cited by 8 · see citing works
Effect of Fuzhisan on Alzheimers disease model mice
Man, S. W. (2007) · Zhongguo yaolixue tongbao · Cited by 2 · see citing works
Flagged first, then by citations
1 of the 31 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Neuroprotective Natural Products for Alzheimer’s Disease
Chen, X., Drew, J., Berney, W., & Lei, W. (2021) · Cells · doi:10.3390/cells10061309 · Cited by 236 · see citing works
Oxidative stress and mRNA expression of acetylcholinesterase in the leukocytes of ischemic patients
Işık, M., Beydemir, Ş., Yılmaz, A., Naldan, M. E., Duran, H. E., & Gülçın, İ. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.01.003 · Cited by 98 · see citing works
Şenol, F. S., Orhan, İ. E., Yılmaz, G., Çiçek, M., & Şener, B. (2009) · Food and Chemical Toxicology · doi:10.1016/j.fct.2009.12.004 · Cited by 94 · see citing works
Islam, F., Khadija, J. F., Harun-Or-Rashid, M., Rahaman, M. S., Nafady, M. H., Islam, M. R., Akter, A., Emran, T. B., Wilairatana, P., & Mubarak, M. S. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5100904 · Cited by 85 · see citing works
Lan, Z., Chen, L., Fu, Q., Ji, W., Wang, S.-Y., Liang, Z., Qu, R., Kong, L., & Ma, S.-P. (2013) · Brain Research · doi:10.1016/j.brainres.2012.12.040 · Cited by 51 · see citing works
Cioancă, O., Hăncianu, M., Mihăşan, M., & Hriţcu, L. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1550-0 · Cited by 47 · see citing works
Shi, S.-H., Zhao, X., Liu, B., Li, H., Liu, A.-J., Wu, B., Bi, K.-S., & Jia, Y. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/451802 · Cited by 40 · see citing works
Molecular Imaging in Traditional Chinese Medicine Therapy for Neurological Diseases
Wang, Z., Wan, H., Li, J., Zhang, H., & Tian, M. (2013) · BioMed Research International · doi:10.1155/2013/608430 · Cited by 33 · see citing works
GUO, P., WANG, D., WANG, X., FENG, H., TANG, Y., SUN, R., ZHENG, Y., DONG, L., ZHAO, J., ZHANG, X., et al. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.4957 · Cited by 30 · see citing works
Self-citationBi, M., Tong, S., Zhang, Z., Ma, Q., Zhang, S., Luo, Z., Zhang, Y., Li, X., & Wang, D. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.06.036 · Cited by 30 · see citing works
Self-citationThe Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment
Zieneldien, T., Kim, J., & Cao, C. (2022) · Geriatrics · doi:10.3390/geriatrics7020024 · Cited by 29 · see citing works
“Fuzhisan, a Chinese herbal complex comprising Anemone altaica in the Araceae family, Glycyrrhiza uralensis in the Leguminosae family, Scutellaria baicalensis in the Labiatae family, and Ginseng root in the Araliaceae family, has been clinically utilized for senile dementia [75].”
BackgroundHOU, X.-Q., Yan, R., Yang, C., Zhang, L., Su, R., Liu, S., Zhang, S., He, W.-Q., Fang, S., Cheng, S., et al. (2013) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2013.1608 · Cited by 29 · see citing works
Analysis of Fuzhisan and quantitation of baicalin and ginsenoside Rb1 by HPLC-DAD-ELSD
Zhao, J., Wang, D., Duan, S., Wang, J., Bai, J., & Li, W. (2009) · Archives of Pharmacal Research · doi:10.1007/s12272-009-1703-2 · Cited by 23 · see citing works
Self-citationNatural products improve healthspan in aged mice and rats: A systematic review and meta-analysis
Musillo, C., Borgi, M., Saul, N., Möller, S., Luyten, W. H. M. L., Berry, A., & Cirulli, F. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.12.001 · Cited by 22 · see citing works
Zhang, Z.-X., Zhao, R., Wang, D., & Wang, A.-N. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.09.003 · Cited by 20 · see citing works
Self-citationYang, H., Wen, S., Zhang, G., Wang, T., Hu, F.-X., Li, X., & Wang, D. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2010.12.004 · Cited by 20 · see citing works
Self-citationGao, R., Wang, Y., Pan, Q., Huang, G., Li, N., Mou, J., & Wang, D. (2015) · Europe PMC (PubMed Central) · Cited by 13 · see citing works
Self-citationLi, J., Wan, H., Zhang, H., & Tian, M. (2011) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2011.06.004 · Cited by 12 · see citing works
Zhang, Z., Zhao, R., Tang, Y., Wen, S., Wang, D., & Qi, J. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0405-6 · Cited by 11 · see citing works
Self-citationRetractedZhang, Z., Zhao, R., Tang, Y., Wen, S., Wang, D., & Qi, J. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0721-5 · Cited by 9 · see citing works
Self-citationRetractedAlsenani, F. (2024) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2024.103998 · Cited by 7 · see citing works
Zhang, Z.-X., Zhao, R., Wang, D., & Li, Y.-B. (2016) · Neurochemical Research · doi:10.1007/s11064-016-2028-4 · Cited by 7 · see citing works
Self-citationSri, R. S., Pavithra, T., Vinciya, T., Kumar, V. S., Harikrishnan, N., Begum, R. F., & Singh, S. A. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1561702 · Cited by 8 · see citing works
Lin, L.-F., & Luo, H.-M. (2011) · Neuroscience Bulletin · doi:10.1007/s12264-011-1040-6 · Cited by 6 · see citing works
The Use of Natural Products for Preventing Cognitive Decline/Providing Neuroprotection
Tabatabaei‐Malazy, O., Azizi, B., & Abdollahi, M. R. (2024) · Handbook of experimental pharmacology · doi:10.1007/164_2024_732 · Cited by 3 · see citing works
Zhang, Z., Zhang, S., Liu, S., He, Y., & Wang, A. (2024) · Brain Research · doi:10.1016/j.brainres.2024.149436 · Cited by 1 · see citing works
Zhang, G., Lin, L., Yang, H., Wang, T., Li, X., Li, G., Wen, S., & Wang, D. (2011) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2011.08.061 · Cited by 1 · see citing works
Self-citationNatural Product-Based Drug Discovery
Ahmad, S. (2015) · Reviews in Cell Biology and Molecular Medicine · doi:10.1002/3527600906.mcb.201500005 · Cited by 1 · see citing works
Herbal medicine for mild cognitive impairment: Neuroimaging perspectives
Zhang, Y.-Q. (2026) · World Journal of Clinical Cases · doi:10.12998/wjcc.v14.i16.118410
- Authors
- Li, X. L., Wang, D. S., Zhao, B. Q., Li, Q., Qu, H. Y., Zhang, T., Zhou, J. P., & Sun, M. J.
- Affiliations
- Harbin Medical University (CN)
- Academy of Military Medical Sciences (CN)
- Corresponding author
- Wang, De Sheng
- ORCID
- Zhang, Ting
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 43
- Issue
- 9
- Pages
- 853-858
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2115461550
- Cited by
- 29
- References
- 31
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2022: 2 · 2021: 1 · 2020: 1 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- 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
- Chinese herbal medicine, aging, cognitive impairment, memory impairment, cholinergic system, acetylcholine, brain glucose metabolism, Alzheimer's disease, aged rats, hippocampus, learning and memory, neuroprotection, aqueous herbal extract, small animal PET, SPECT imaging, cerebral blood flow, amyloid-beta
- MeSH terms
- Acetylcholine, Aging, Animals, Brain, Choline O-Acetyltransferase, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Drugs, Chinese Herbal, Glucose, Hippocampus, Male, Phytotherapy, Reaction Time, Rats, Wistar, Maze Learning, Positron-Emission Tomography, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review