Stachys sieboldii Extract Supplementation Attenuates Memory Deficits by Modulating BDNF-CREB and Its Downstream Molecules, in Animal Models of Memory Impairment
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Cholinergic dysfunction, impaired brain-derived neurotrophic factor and cAMP response element binding protein (BDNF-CREB) signaling are one of the major pathological hallmarks of cognitive impairment. Therefore, improving cholinergic neurotransmission, and regulating the BDNF-CREB pathway by downregulating apoptosis genes is one strategy for inhibiting the etiology of dementia. This study evaluates the potential effects of Stachys sieboldii MIQ (SS) extract against cognitive dysfunction and its underlying mechanisms. SS supplementation for 33 days improved scopolamine-induced memory impairment symptoms in Morris water maze test and Y-maze test. SS reduced the acetylcholineesterase activity and significantly increase acetylcholine and cholineacetyltransferase activity in the brain. In the subsequent mechanism study, SS regulated the mRNA expression level of neuronal plasticity molecules such as (nerve growth factor) NGF, BDNF, CREB, and its downstream molecules such as Bcl-2 and Egr-1 by downregulating the neuronal apoptosis targets in both hippocampus and frontal cortex. Additionally, inward currents caused by SS in hippocampal CA1 neurons was partially blocked by the GABA receptor antagonist picrotoxin (50 μM), suggesting that SS acts on synaptic/extrasynaptic GABAA receptors. These findings indicate that SS may function in a way that is similar to nootropic drugs by inhibiting cholinergic abnormalities, and neuronal apoptosis targets and ultimately increasing the expression of BDNF-CREB.
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Stachys sieboldii ethanolic extract at 250 and 500 mg/kg improved memory, reduced AChE activity, increased acetylcholine and catalase levels, and enhanced neuroplasticity in rats and mice.
“The ethanolic extract of Stachys sieboldii (250 and 500 mg/kg) improved memory, reduced AChE activity, increased acetylcholine (ACh) and antioxidant enzyme catalase (CAT) levels, and enhanced neuroplasticity in rats and mice, suggesting neuroprotective effects [48].”
From Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review (2025) · cites this paper as [48]
Methods §§2.1 and 2.3 describe a 20% ethanol extract given at 250 mg/kg to rats and 500 mg/kg to mice. The Discussion reports improved memory, increased acetylcholine, inhibited AChE, and changes in genes associated with neuronal plasticity. But Methods §2.7 defines CAT as choline acetyltransferase, not the antioxidant enzyme catalase; the claim misidentifies what increased. (LLM, conf=0.94)
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Cites
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180 · see citing works
SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE
DAVIES, P. (1976) · The Lancet · doi:10.1016/s0140-6736(76)91936-x · Cited by 3,565 · see citing works
Neurotrophin-regulated signalling pathways
Reichardt, L. F. (2006) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2006.1894 · Cited by 2,195 · see citing works
Mesulam, M. ‐., Mufson, E. J., Levey, A. I., & Wainer, B. H. (1983) · Journal of Comparative Neurology · doi:10.1002/cne.902140206 · Cited by 1,962 · see citing works
Freireich, E. J., Gehan, E. A., Rall, D. P., Schmidt, L. H., & Skipper, H. E. (1966) · PubMed · Cited by 1,380 · see citing works
Apoptosis and Caspases in Neurodegenerative Diseases
Friedlander, R. M. (2003) · New England Journal of Medicine · doi:10.1056/nejmra022366 · Cited by 873 · see citing works
Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline
Ballinger, E. C., Ananth, M. R., Talmage, D. A., & Role, L. W. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.006 · Cited by 735 · see citing works
Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications
Mufson, E. J., Counts, S., Perez, S. E., & Ginsberg, S. D. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.11.1703 · Cited by 589 · see citing works
Brain-Derived Neurotrophic Factor/TrkB Signaling in Memory Processes
Yamada, K., & Nabeshima, T. (2003) · Journal of Pharmacological Sciences · doi:10.1254/jphs.91.267 · Cited by 585 · see citing works
Neuronal caspase-3 signaling: not only cell death
D’Amelio, M., Cavallucci, V., & Cecconi, F. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.180 · Cited by 526 · see citing works
The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive ImpairmentPreprint
Tarawneh, R. M., & Holtzman, D. M. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006148 · Cited by 474 · see citing works
NGF Is Essential for Hippocampal Plasticity and Learning
Conner, J. M., Franks, K. M., Titterness, A. K., Russell, K., Merrill, D. A., Christie, B. R., Sejnowski, T. J., & Tuszynski, M. H. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2594-09.2009 · Cited by 189 · see citing works
Effects of morphine and its withdrawal on Y-maze spatial recognition memory in mice
Ma, M. X., Chen, Y. M., He, J., Zeng, T., & Wang, J. H. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.05.020 · Cited by 168 · see citing works
Li, Q., Zhao, H., Zhang, Z. F., Liu, Z. G., Pei, X., Wang, J. B., Cai, M. Y., & Li, Y. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.02.008 · Cited by 130 · see citing works
Altered Levels of Acetylcholinesterase in Alzheimer Plasma
García‐Ayllón, M., Llena, I. R., Serra‐Basante, C., Alom, J., Boopathy, R., & Sáez‐Valero, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008701 · Cited by 126 · see citing works
Endogenous BDNF is required for long-term memory formation in the rat parietal cortexPreprint
Alonso, M., Bekinschtein, P., Cammarota, M., Vianna, M. R. M. R., Izquierdo, I., & Medina, J. H. (2005) · Learning & Memory · doi:10.1101/lm.27305 · Cited by 124 · see citing works
Nine phenethyl alcohol glycosides from Stachys sieboldii
Nishimura, H., Sasaki, H., Inagaki, N., Chin, M., Chen, Z., & Mitsuhashi, H. (1991) · Phytochemistry · doi:10.1016/0031-9422(91)85288-b · Cited by 102 · see citing works
Maddox, S. A., Monsey, M. S., & Schafe, G. E. (2010) · Learning & Memory · doi:10.1101/lm.1980211 · Cited by 99 · see citing works
Batool, Z., Sadir, S., Liaquat, L., Tabassum, S., Madiha, S., Rafiq, S., Tariq, S., Batool, T. S., Saleem, S., Naqvi, F. F., et al. (2015) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2015.11.001 · Cited by 99 · see citing works
Shaw, K. N., Commins, S., & O’Mara, S. M. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02643.x · Cited by 94 · see citing works
Porcher, C., Hatchett, C., Longbottom, R. E., McAinch, K., Sihra, T. S., Moss, S. J., Thomson, A. M., & Jovanovic, J. N. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.201582 · Cited by 91 · see citing works
Modulation of Ionotropic GABA Receptors by Natural Products of Plant Origin
Johnston, G. A. R., Hanrahan, J. R., Chebib, M., Duke, R. K., & Mewett, K. N. (2006) · Advances in pharmacology · doi:10.1016/s1054-3589(06)54012-8 · Cited by 90 · see citing works
Caspases in synaptic plasticity
Li, Z., & Sheng, M. (2012) · Molecular Brain · doi:10.1186/1756-6606-5-15 · Cited by 87 · see citing works
Pharmacological effects of Withania somnifera root extract on GABAA receptor complex.
Mehta, A. K., Binkley, P. A., Ss, G., & Ticku, M. K. (1991) · PubMed · Cited by 77 · see citing works
Hayashi, K., Nagamatsu, T., Ito, M., Hattori, T., & Suzuki, Y. (1994) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.65.143 · Cited by 72 · see citing works
Borba, E. M., Duarte, J. A., Bristot, G., Scotton, E., Camozzato, A. L., & Chaves, M. L. F. (2016) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000450601 · Cited by 67 · see citing works
Yin, J., Yang, G., Wang, S., & CHEN, Y. (2006) · Talanta · doi:10.1016/j.talanta.2006.03.027 · Cited by 64 · see citing works
Sattayasai, J., Chaonapan, P., Arkaravichie, T., Soi‐ampornkul, R., Junnu, S., Charoensilp, P., Samer, J., Jantaravinid, J., Masaratana, P., Suktitipat, B., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0085053 · Cited by 57 · see citing works
Um, M. Y., Lim, D. W., Son, H. J., Cho, S., & Lee, C.-H. (2017) · Journal of Functional Foods · doi:10.1016/j.jff.2017.10.014 · Cited by 57 · see citing works
Studies on Stachys sieboldii MIQ. II. Anti-anoxia Action and the Active Constituents
Yamahara, J., Kitani, T., Kobayashi, H., & Kawahara, Y. (1990) · YAKUGAKU ZASSHI · doi:10.1248/yakushi1947.110.12_932 · Cited by 56 · see citing works
Bhattarai, J. P., Park, S. A., & Han, S. K. (2009) · Phytotherapy Research · doi:10.1002/ptr.3088 · Cited by 50 · see citing works
Self-citationBrady, M. L., Pilli, J., Lorenz‐Guertin, J. M., Das, S., Moon, C. E., Graff, N., & Jacob, T. C. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.10.022 · Cited by 49 · see citing works
Effect of insulin and melatonin on acetylcholinesterase activity in the brain of amnesic mice
Agrawal, R., Tyagi, E., Shukla, R., & Nath, C. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.01.015 · Cited by 48 · see citing works
Potentiation of NMDA Receptors byWithania somniferaon Hippocampal CA1 Pyramidal Neurons
Bhattarai, J. P., Park, S. J., & Han, S. K. (2013) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x13500365 · Cited by 16 · see citing works
Self-citationGonzález, M. I. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2014.04.006 · Cited by 14 · see citing works
Abinaya, R., Kim, M. K., Lee, S.-J., jeong, E.-S., & Cha, Y. (2017) · Journal of Food Biochemistry · doi:10.1111/jfbc.12411 · Cited by 11 · see citing works
Self-citationAbinaya, R., Pichiah, P. B. T., Thomas, S. S., Kim, S., Han, D.-W., Song, Y., Oh, S., & Cha, Y. (2016) · Journal of Food Biochemistry · doi:10.1111/jfbc.12324 · Cited by 10 · see citing works
Self-citationHan, S. K., & Bhattarai, J. P. (2014) · Journal of Ayurveda and Integrative Medicine · doi:10.4103/0975-9476.146541 · Cited by 8 · see citing works
Self-citationCanevelli, M., Blasimme, A., & Cesari, M. (2017) · European Journal of Epidemiology · doi:10.1007/s10654-016-0222-y · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Muhammad, T., Ikram, M. A., Ullah, R., Rehman, S. U., & Kim, M. (2019) · Nutrients · doi:10.3390/nu11030648 · Cited by 445 · see citing works
Self-citationRetractedGenus Stachys: A Review of Traditional Uses, Phytochemistry and Bioactivity
Tomou, E., Barda, C., & Skaltsa, H. D. (2020) · Medicines · doi:10.3390/medicines7100063 · Cited by 99 · see citing works
Interleukin‐17 and ischaemic stroke
Zhang, Q., Liao, Y., Liu, Z., Dai, Y., Li, Y., Li, Y., & Tang, Y. (2020) · Immunology · doi:10.1111/imm.13265 · Cited by 79 · see citing works
Theobromine Improves Working Memory by Activating the CaMKII/CREB/BDNF Pathway in Rats
Islam, R., Matsuzaki, K., Sumiyoshi, E., Hossain, M. E., Hashimoto, M., Katakura, M., Sugimoto, N., & Shido, O. (2019) · Nutrients · doi:10.3390/nu11040888 · Cited by 62 · see citing works
Yan, T., He, B., Xu, M., Wu, B., Xiao, F., Bi, K., & Jia, Y. (2019) · Phytotherapy Research · doi:10.1002/ptr.6300 · Cited by 55 · see citing works
Gong, Y., Chen, J., Jin, Y., Wang, C., Zheng, M., & He, L. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107899 · Cited by 44 · see citing works
ALNasser, M. N., Alboraiy, G. M., Alsowig, E. M., & Alqattan, F. M. (2025) · Brain Sciences · doi:10.3390/brainsci15020215 · Cited by 35 · see citing works
Zou, W., Liu, J., Jiao, Y., Sun, Y., Chen, N., Zhou, L., Guan, X., Wang, J., Wei, W., Han, C., et al. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.339002 · Cited by 28 · see citing works
Genus Stachys—Phytochemistry, Traditional Medicinal Uses, and Future Perspectives
Pashova, S., Karcheva-Bahchevanska, D. P., Ivanov, K., & Ivanova, S. (2024) · Molecules · doi:10.3390/molecules29225345 · Cited by 27 · see citing works
Tang, Q., Ke, H. Q., Wu, C., Zeng, J., Li, Z., Liu, Y., Feng, S., Xue, Q., & Xu, X. (2019) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2019.111925 · Cited by 26 · see citing works
Effect of vitamin D supplementation on CREB-TrkB-BDNF pathway in the hippocampus of diabetic rats.
Nadimi, H., Djazayery, A., Javanbakht, M. H., Dehpour, A. R., Ghaedi, E., Derakhshanian, H., Mohammadi, H., Mousavi, S. N., & Djalali, M. (2020) · PubMed Central · doi:10.22038/ijbms.2019.38170.9068 · Cited by 24 · see citing works
Zhang, Q., Li, Y., Wang, X., Yin, C., Zhou, Q., Guo, J., Zhao, J., Xian, X., Hou, Z., & Wang, Q. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.990679 · Cited by 22 · see citing works
Sohn, E., Lim, H.-S., Kim, Y. J., Kim, B., Kim, J., & Jeong, S. (2019) · Nutrients · doi:10.3390/nu11061205 · Cited by 22 · see citing works
Lee, J. K., Lee, J., Kim, Y.-K., Lee, Y., & Ha, J. (2020) · Nutrients · doi:10.3390/nu12072063 · Cited by 18 · see citing works
Lee, H.-J., Kim, H. L., Lee, D., Lee, D., Choi, B., & Yang, S. H. (2021) · Applied Sciences · doi:10.3390/app11094286 · Cited by 13 · see citing works
Xu, L., Wang, S., Zhang, L., Liu, B., Shang, Z., & Yao, M. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00048 · Cited by 9 · see citing works
Sasai, M., Kato, M., Ohsawa, K., Sashihara, K., Nakamura, Y., & Kaneko, T. (2020) · Bioscience Biotechnology and Biochemistry · doi:10.1093/bbb/zbaa117 · Cited by 8 · see citing works
Zhang, Q., Li, Y., Yin, C., Gao, M., Yu, J., Guo, J., Xian, X., Hou, Z., & Wang, Q. (2022) · Bioengineered · doi:10.1080/21655979.2022.2090608 · Cited by 8 · see citing works
Assaran, A. H., Hosseini, M., Shirazinia, M., Ghalibaf, M. H. E., Beheshti, F., Mobasheri, L., Mirzavi, F., & Rajabian, A. (2024) · Current Pharmaceutical Design · doi:10.2174/0113816128269289231226115446 · Cited by 5 · see citing works
Ji, S., Wu, Y., Zhu, R., Guo, D., Jiang, Y., Huang, L., Ma, X., & Yu, L. (2023) · Gerontology · doi:10.1159/000531194 · Cited by 6 · see citing works
Izumi, Y., Kataoka, H., Takada‐Takatori, Y., Kōyama, Y., Irie, K., Akaike, A., & Kume, T. (2023) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b23-00383 · Cited by 4 · see citing works
Gwon, Y., So, K.-K., Chun, J., & Kim, D. (2024) · Journal of Biological Engineering · doi:10.1186/s13036-024-00429-0 · Cited by 4 · see citing works
Brinza, I., Stache, A. B., Mihăşan, M., Gorgan, L., Raey, M. A. E., El‐Kashak, W. A., Eldahshan, O. A., & Hriţcu, L. (2025) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273345712250119200430 · Cited by 4 · see citing works
Shi, J., Chen, M., Zhang, Y., Fan, X., Wang, L. Y., & Liao, H. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06877-w · Cited by 3 · see citing works
Wiśniewski, R., & Harasym, J. (2024) · Molecules · doi:10.3390/molecules29153525 · Cited by 3 · see citing works
Bakhtazad, A., Taei, A. A., Parvizi, F., Kadivar, M., & Farahmandfar, M. (2023) · Alcohol · doi:10.1016/j.alcohol.2023.08.004 · Cited by 3 · see citing works
Pozdnyakova, Y. V., & Murzatayeva, A. (2025) · Biology · doi:10.3390/biology14040359 · Cited by 2 · see citing works
Changes in Organ Systems over the Lifespan
Tan, B. L., & Norhaizan, M. E. (2021) · Springer eBooks · doi:10.1007/978-3-030-82859-2_2
Stachys affinis (Chinese artichoke)
CABI (2019) · CABI Compendium · doi:10.1079/cabicompendium.93984415
Lin, L., Zhu, C., Yan, B., Yu, P., Yang, L., Huang, W., & Chen, J. (2024) · Clinics · doi:10.1016/j.clinsp.2024.100560
- Authors
- Ravichandran, V. A., Kim, M., Han, S. K., & Cha, Y. S.
- Affiliations
- Department of Food Science and Human Nutrition, Chonbuk National University, 664-14 Duckjin-dong, Jeonju, Jeonbuk 561-756, Korea
- Rural Development Administration (KR)
- Jeonbuk National University (KR)
- Corresponding author
- Cha, Youn Soo
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2018-07-17
- Volume
- 10
- Issue
- 7
- Pages
- 917
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC6073797
- OpenAlex
- W2883631299
- Cited by
- 28
- References
- 39
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 5 · 2019: 6
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Korea Institute for Advancement of Technology
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Stachys sieboldii, plant extract supplementation, memory impairment, cholinergic dysfunction, acetylcholinesterase, choline acetyltransferase, acetylcholine, neuronal apoptosis, Bcl-2, EGR1, nerve growth factor, hippocampus, frontal cortex, GABAA receptor, picrotoxin, nootropic effects, dementia, cognitive impairment
- MeSH terms
- Acetylcholinesterase, Animals, Choline O-Acetyltransferase, Frontal Lobe, Hippocampus, Male, Memory Disorders, Mice, Inbred ICR, Nerve Tissue Proteins, Plant Extracts, Random Allocation, Rats, Sprague-Dawley, Cyclic AMP Response Element-Binding Protein, Gene Expression Regulation, Developmental, Nootropic Agents, Brain-Derived Neurotrophic Factor, Dietary Supplements, Ethnopharmacology, Stachys, Medicine, Korean Traditional, Republic of Korea, Cholinergic Neurons
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