Terpenoid-rich Elettaria cardamomum extract prevents Alzheimer-like alterations induced in diabetic rats via inhibition of GSK3β activity, oxidative stress and pro-inflammatory cytokines
Abstract
Purpose Recent studies suggested that the non-familiar form of Alzheimer's disease (AD) could be consequence of metabolic syndrome and neuroinflammation. Elettaria cardamomum extract (EC) has exhibited antidiabetic, antioxidant and anti-inflammatory properties. This research was conducted to evaluate the effects of EC on AD-like alterations in rats induced by high fructose and high fat diet coupled with a single small dose of STZ (25 mg/kg) (T2DM rats).Methods Phytochemical analysis was carried out. Behavioral tests, immunohistochemical examination, biochemical analysis and gene expression determination were performed in treated and controls rats.Results The majority of EC compounds were terpenoids. EC extract administration for 8 weeks attenuated AD-like alterations. It reversed a T2DM-induced decline in cognitive functions in passive avoidance task and Morris water maze test. It significantly lowered the elevated hippocampal level of AChE activity and caspase-3 activity, an indicator of degeneration in T2DM rats Also, it reduced the accumulation of Aβ and p-tau in the brain of T2DM rats. Furthermore, it elevated the suppressed glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). EC treatment reduced hippocampal lipid peroxidation marker malondialdehyde (MDA) and augmented antioxidant defensive system, including superoxide dismutase (SOD) and reduced glutathione (GSH). Meanwhile, it lowered hippocampal TNFα, IL β1but not IL6 and reduced GSK-3β in brainT2D rats.Conclusion EC treatment could ameliorate AD-like alterations in T2DM rats through activation of blunted insulin signal transduction in the brain, attenuation of associated oxidative stress and neuroinflammation.
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E. cardamomum improves glucose intolerance and memory in amnesic mice.
“It also improves glucose intolerance, and memory in amnesic mice (Gomaa et al., 2019).”
From Alpha-terpinyl acetate: A natural monoterpenoid from Elettaria cardamomum as multi-target directed ligand in Alzheimer’s disease (2020) · cites this paper as Gomaa et al., 2019
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
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction
Ohkawa, H., Ohishi, N., & Yagi, K. (1979) · Analytical Biochemistry · doi:10.1016/0003-2697(79)90738-3 · Cited by 29,460 · see citing works
A new and rapid colorimetric determination of acetylcholinesterase activity
Ellman, G. L., Courtney, K. D., Andres, V., & Featherstone, R. M. (1961) · Biochemical Pharmacology · doi:10.1016/0006-2952(61)90145-9 · Cited by 27,221 · see citing works
Improved method for the determination of blood glutathione.
Beutler, E., Duron, O., & KELLY, B. M. (1963) · PubMed · Cited by 6,932 · see citing works
Estimation of total flavonoid content in propolis by two complementary colometric methods
Chang, C.-C., Yang, M.-H., Wen, H.-M., & Chern, J.-C. (2020) · Journal of Food and Drug Analysis · doi:10.38212/2224-6614.2748 · Cited by 4,106 · see citing works
Nishikimi, M., Rao, N. A., & Yagi, K. (1972) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(72)80218-3 · Cited by 4,091 · see citing works
Increased Risk of Type 2 Diabetes in Alzheimer Disease
Janson, J., Laedtke, T., Parisi, J. E., O’Brien, P., Petersen, R. C., & Butler, P. C. (2004) · Diabetes · doi:10.2337/diabetes.53.2.474 · Cited by 950 · see citing works
Oxidative Stress and the Pathogenesis of Alzheimer's Disease
Zhao, Y., & Zhao, B. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/316523 · Cited by 855 · see citing works
Biessels, G. J., Strachan, M. W. J., Visseren, F. L. J., Kappelle, L. J., & Whitmer, R. A. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70088-3 · Cited by 555 · see citing works
Mucke, L. (2009) · Nature · doi:10.1038/461895a · Cited by 456 · see citing works
Molecular Pathogenesis of Alzheimer's Disease: An Update
Sanabria‐Castro, A., Echeverría, I. A., & Bonilla, C. M. (2017) · Annals of Neurosciences · doi:10.1159/000464422 · Cited by 418 · see citing works
Dysfunction of NMDA receptors in Alzheimer’s disease
Zhang, Y., Li, P., Feng, J., & Wu, M. (2016) · Neurological Sciences · doi:10.1007/s10072-016-2546-5 · Cited by 282 · see citing works
Inflammatory Aspects of Alzheimer Disease and Other Neurodegenerative Disorders
Schwab, C., & McGeer, P. L. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-13402 · Cited by 234 · see citing works
The Rat Model of Type 2 Diabetic Mellitus and Its Glycometabolism Characters
Zhang, F., Ye, C., Li, G., Ding, W., Zhou, W., Zhu, H., Chen, G., Luo, T., Guang, M., Liu, Y., et al. (2003) · EXPERIMENTAL ANIMALS · doi:10.1538/expanim.52.401 · Cited by 152 · see citing works
Insulin resistance and cognitive dysfunction
Ma, L., Wang, J., & Li, Y. (2015) · Clinica Chimica Acta · doi:10.1016/j.cca.2015.01.027 · Cited by 145 · see citing works
Metabolism-Centric Overview of the Pathogenesis of Alzheimer's Disease
Kang, S., Lee, Y., & Lee, J. E. (2017) · Yonsei Medical Journal · doi:10.3349/ymj.2017.58.3.479 · Cited by 143 · see citing works
Shankar, G. M., Leissring, M. A., Adame, A., Sun, X., Spooner, E., Masliah, E., Selkoe, D. J., Lemere, C. A., & Walsh, D. M. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.07.021 · Cited by 123 · see citing works
Felice, F. G. D., & Lourenco, M. V. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00094 · Cited by 120 · see citing works
Wang, X., Ge, A., Cheng, M., et al. (2012) · Experimental Diabetes Research · doi:10.1155/2012/847246 · Cited by 106 · see citing works
Rahman, M. M., Alam, M. A., Ulla, A., Sumi, F. A., Subhan, N., Khan, T., Sikder, B., Hossain, H., Reza, H. M., & Alam, M. A. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0539-x · Cited by 106 · see citing works
Busquets, O., Ettcheto, M., Pallàs, M., Beas‐Zárate, C., Verdaguer, E., Auladell, C., Folch, J., & Camins, A. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.11.002 · Cited by 104 · see citing works
Barichello, T., dos Santos, I., Savi, G. D., Simões, L. R., Silvestre, T., Comim, C. M., Sachs, D., Teixeira, M. M., Teixeira, A. L., & Quevedo, J. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.02.009 · Cited by 72 · see citing works
Anderson, R. A., Qin, B., Canini, F., Poulet, L., & Roussel, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083243 · Cited by 71 · see citing works
Xi, D., Keeler, B. E., Zhang, W., Houlé, J. D., & Gao, W. (2008) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2008.09.013 · Cited by 66 · see citing works
New Therapeutic Targets in Alzheimer's Disease
Coman, H. G., & Nemeş, B. (2017) · International journal of gerontology · doi:10.1016/j.ijge.2016.07.003 · Cited by 62 · see citing works
Lin, H.-B., Yang, X., Li, T., Cheng, Y., Zhang, H., & Xu, J. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1499-2 · Cited by 57 · see citing works
Shamim, D., & Laskowski, M. C. (2017) · Journal of Central Nervous System Disease · doi:10.1177/1179573517722512 · Cited by 56 · see citing works
Kandikattu, H. K., Rachitha, P., Jayashree, G. V., Krupashree, K., Sukhith, M., Majid, A., Amruta, N., & Khanum, F. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.04.049 · Cited by 52 · see citing works
Lee, T.-T., Huang, C.-C., Shieh, X.-H., et al. (2010) · International Journal of Environmental Science and Development · doi:10.7763/ijesd.2010.v1.2 · Cited by 49 · see citing works
Kazemi, S., yaghooblou, F., Siassi, F., Foroushani, A. R., Ghavipour, M., Koohdani, F., & Sotoudeh, G. (2017) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.8414 · Cited by 48 · see citing works
Bhat, G. N., Nayak, N., Vinodraj, K., Chandralekha, N., Mathai, P., & Cherian, J. (2015) · Journal of Advanced Pharmaceutical Technology amp Research · doi:10.4103/2231-4040.157981 · Cited by 44 · see citing works
Lin, C. H., & Lee, E. H. Y. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3380-11.2012 · Cited by 31 · see citing works
Winarsi, H., Sasongko, N. D., Purwanto, A., & Nuraeni, I. (2014) · International Food Research Journal · Cited by 29 · see citing works
Strekalova, T. V., Markova, N., Shevtsova, E. F., Zubareva, O. E., Bakhmet, А. А., Steinbusch, H. W. M., Бачурин, С. О., & Lesch, K. (2016) · Neural Plasticity · doi:10.1155/2016/5098591 · Cited by 29 · see citing works
Validation of reference genes for quantitative real-time PCR in valproic acid rat models of autism
Zhou, J., Zhang, X., Ren, J., et al. (2016) · Molecular Biology Reports · doi:10.1007/s11033-016-4015-x · Cited by 27 · see citing works
Gomaa, A. A., Farghaly, H. S. M., Elsers, D., Farrag, M. M. Y., & Al-Zokeim, N. I. (2018) · Inflammopharmacology · doi:10.1007/s10787-018-0519-4 · Cited by 27 · see citing works
Self-citationLee, C.-W., Lee, H., Cha, Y., et al. (2013) · Preventive Nutrition and Food Science · doi:10.3746/pnf.2013.18.3.169 · Cited by 22 · see citing works
Li, W., Tao, S., Wu, Q., Wu, T., Tao, R. N., & Fan, J. (2017) · Journal of Surgical Research · doi:10.1016/j.jss.2017.06.090 · Cited by 22 · see citing works
Shin, S.-C., & Lee, D. (2013) · Chinese Journal of Natural Medicines · doi:10.1016/s1875-5364(13)60057-6 · Cited by 14 · see citing works
Shin, S.-C., & Lee, D. (2014) · Chinese Journal of Natural Medicines · doi:10.3724/sp.j.1009.2013.00391 · Cited by 9 · see citing works
Standardization of Euphorbia hirta with Chemical Compounds Identification (GC-MS)
Ping, K. Y., Ibrahim, D., Yusuf, U. K., et al. (2012) · International Journal of Phytomedicine · Cited by 8 · see citing works
Kunwar, T., Kumar, N., Kothiyal, P., Guru, S., & C., R. (2014) · Cited by 8 · see citing works
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Sharifi-Rad, J., Rapposelli, S., Sestito, S., Herrera-Bravo, J., Arancibia-Diaz, A., Salazar, L. A., Yeskaliyeva, B., Beyatli, A., Leyva-Gómez, G., González-Contreras, C., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12091515 · Cited by 125 · see citing works
Chowdhury, S., & Kumar, S. (2020) · Journal of Functional Foods · doi:10.1016/j.jff.2020.103892 · Cited by 69 · see citing works
- Authors
- Gomaa, A. A., Makboul, R. M., El-Mokhtar, M. A., Abdel-Rahman, E. A., Ahmed, I. A., & Nicola, M. A.
- Affiliations
- Assiut University (EG)
- Corresponding author
- Gomaa, Adel A.
- Venue
- Cytokine
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 113
- Pages
- 405-416
- ISSN
- 1043-4666 (ISSN-L)
- OpenAlex
- W2898140444
- Cited by
- 45
- References
- 43
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 8 · 2023: 7 · 2022: 12 · 2021: 6 · 2020: 2 · 2019: 1
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cytokine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- The Scientific & The Technology Development Fund
- Ministry of State for Scientific Research (6897)
- 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 › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- cardamom, cardamom extract, terpenoids, Alzheimer's disease, type 2 diabetes, streptozotocin-induced diabetes, neuroinflammation, oxidative stress, GSK3β, amyloid-beta, tau phosphorylation, acetylcholinesterase, caspase-3, glutamate receptors, insulin signaling, cognitive impairment, neuroprotection, metabolic syndrome
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Animals, Brain, Diabetes Mellitus, Experimental, Inflammation, Male, Plant Extracts, Terpenes, Cytokines, Amyloid beta-Peptides, Rats, Wistar, Oxidative Stress, Elettaria, Rats
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