Neuroprotective evaluation of diospyrin against drug-induced Alzheimer’s disease
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease linked to memory impairment. A current investigation was performed to assess the neuroprotective effect of Diospyrin, a novel therapeutic agent, for the curing of Alzheimer's disease. For this purpose, in-vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory assays and antioxidant studies were conducted, whereas in-vivo studies involved different behavioral animal models tests such as elevated plus maze (EPM), morris water maze (MWM) and paddling Y-maze test. Results of the in-vitro analysis showed IC 50 values of 95 μg/mL for AChE and 110 μg/mL for BChE as compared to the standard drug donepezil (IC 50: 95 & 85 μg/mL, respectively). DPPH antioxidant assay showed a maximum of 72.85% inhibition (IC 50: 139.74 μg/mL) of DPPH-free radicals at the highest concentration of 1000 μg/mL as compared to the ascorbic acid (IC 50: 13.72 μg/mL). Moreover, the in-vivo analysis revealed that diospyrin treatment demonstrated gradual betterment in memory and enhanced motor functionality. On the other hand, the computational analysis also showed that the diospyrin had exceptional binding affinities for both AChE and BChE enzymes. In the net shell, it may be deduced that our compound diospyrin could be a valuable drug candidate in managing neurodegenerative disorders like AD.
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?
Gelsemium sempervirens, Diospyros lotus, and Lavandula angustifolia improved cognitive performance and significantly reduced AChE activity.
“Other notable plant extracts, such as Gelsemium sempervirens, Diospyros lotus, and Lavandula angustifolia, have demonstrated improved cognitive performance and significant reductions in AChE activity, further supporting their potential neuroprotective benefits [59,60,61].”
From Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review (2025) · cites this paper as [60]
Cites
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
Use of a Free Radical Method to Evaluate Antioxidant Activity
Brand-Williams, W., Cuvelier, M. E., & Berset, C. (1995) · LWT - Food Science and Technology · doi:10.1016/s0023-6438(95)80008-5 · Cited by 25,994 · see citing works
Animal research: Reporting <i>in vivo</i> experiments: The ARRIVE guidelines
Kilkenny, C., Browne, W., Cuthill, I. C., Emerson, M., & Altman, D. G. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00872.x · Cited by 3,625 · see citing works
Forecasting the global burden of Alzheimer's disease
Brookmeyer, R., Johnson, E., Ziegler‐Graham, K., & Arrighi, H. M. (2007) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2007.04.381 · Cited by 3,370 · see citing works
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
The cholinergic hypothesis of Alzheimer’s disease: A review of progress
Francis, P. T., Palmer, A. M., Snape, M., & Wilcock, G. K. (1999) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.66.2.137 · Cited by 2,198 · see citing works
Dementia in China: epidemiology, clinical management, and research advances
Jia, L., Quan, M., Fu, Y., Zhao, T., Li, Y., Wei, C., Tang, Y., Qin, Q., Wang, F., Qiao, Y., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30290-x · Cited by 875 · see citing works
The cost of Alzheimer's disease in China and re‐estimation of costs worldwide
Jia, J., Wei, C., Chen, S., Li, F., Tang, Y., Qin, W., Zhao, L., Jin, H., Xu, H., Wang, F., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.12.006 · Cited by 752 · see citing works
The β-Secretase BACE1 in Alzheimer’s Disease
Hampel, H., Vassar, R., De Strooper, B., Hardy, J., Willem, M., Singh, N., Zhou, J., Yan, R., Vanmechelen, E., De Vos, A., et al. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.02.001 · Cited by 694 · see citing works
Hughes, R. N. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.06.006 · Cited by 641 · see citing works
Alzheimer’s disease: Recent treatment strategies
Vaz, M., & Silvestre, S. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173554 · Cited by 547 · see citing works
Itoh, J., NABESHIMA, T., & Kameyama, T. (1990) · Psychopharmacology · doi:10.1007/bf02253713 · Cited by 411 · see citing works
Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling
Wu, Y., Chen, M., & Jiang, J. (2019) · Mitochondrion · doi:10.1016/j.mito.2019.07.003 · Cited by 378 · see citing works
A comprehensive review of monoamine oxidase inhibitors as Anti-Alzheimer’s disease agents: A review
Manzoor, S., & Hoda, N. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112787 · Cited by 264 · see citing works
New approaches to symptomatic treatments for Alzheimer’s disease
Cummings, J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00424-9 · Cited by 226 · see citing works
Gibbons, S., & Udo, E. E. (2000) · Phytotherapy Research · doi:10.1002/(sici)1099-1573(200003)14:2 · Cited by 209 · see citing works
Treatment of Alzheimer’s Disease and Blood–Brain Barrier Drug Delivery
Pardridge, W. M. (2020) · Pharmaceuticals · doi:10.3390/ph13110394 · Cited by 193 · see citing works
The present and future of pharmacotherapy of Alzheimer's disease: a comprehensive review
Anand, A., Patience, A. A., Sharma, N., & Khurana, N. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.09.043 · Cited by 174 · see citing works
Potent Acetylcholinesterase Inhibitors: Potential Drugs for Alzheimer’s Disease
Akıncıoğlu, H., & Gülçın, İ. (2020) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557520666200103100521 · Cited by 158 · see citing works
Apathy and anxiety are early markers of Alzheimer's disease.
Johansson, M., Stomrud, E., Lindberg, O., Westman, E., Johansson, P., van Westen, D., Mattsson, N., & Hansson, O. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.10.008 · Cited by 156 · see citing works
Kabir, M. T., Uddin, M. S., Begum, M. M., Thangapandiyan, S., Rahman, M. S., Aleya, L., Mathew, B., Ahmed, M., Barreto, G. E., & Ashraf, G. M. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191008103141 · Cited by 119 · see citing works
Ahmed, S., Khan, S. T., Zargaham, M. K., Khan, A., Khan, S., Hussain, A., Uddin, J., Khan, A., & Al‐Harrasi, A. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111609 · Cited by 104 · see citing works
Masondo, N. A., Stafford, G. I., Aremu, A. O., & Makunga, N. P. (2018) · South African Journal of Botany · doi:10.1016/j.sajb.2018.09.011 · Cited by 102 · see citing works
Nakhate, K. T., Bharne, A. P., Verma, V. S., Aru, D. N., & Kokare, D. M. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.02.052 · Cited by 100 · see citing works
Seleção de plantas com atividade anticolinasterase para tratamento da doença de Alzheimer
Trevisan, M. T. S., Macedo, F. V. V., van de Meent, M. H. M., Rhee, I. K., & Verpoorte, R. (2003) · Química Nova · doi:10.1590/s0100-40422003000300002 · Cited by 97 · see citing works
Baicalein inhibits heparin-induced Tau aggregation by initializing non-toxic Tau oligomer formation
Sonawane, S. K., Uversky, V. N., & Chinnathambi, S. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00704-3 · Cited by 94 · see citing works
Ali, M., Muhammad, S., Shah, M. R., Khan, A., Rashid, U., Farooq, U., Ullah, F., Sadiq, A., Ayaz, M., Ali, M., et al. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00327 · Cited by 90 · see citing works
Ullah, F., Ayaz, M., Sadiq, A., Hussain, A., Ahmad, S., Imran, M., & Zeb, A. (2015) · Natural Product Research · doi:10.1080/14786419.2015.1057585 · Cited by 82 · see citing works
Alzheimer's Disease Clinical and Research Update for Health Care Practitioners
DeFina, P. A., Moser, R. S., Glenn, M., Lichtenstein, J. D., & Fellus, J. L. (2013) · Journal of Aging Research · doi:10.1155/2013/207178 · Cited by 81 · see citing works
Journey on Naphthoquinone and Anthraquinone Derivatives: New Insights in Alzheimer’s Disease
Campora, M., Francesconi, V., Schenone, S., Tasso, B., & Tonelli, M. (2021) · Pharmaceuticals · doi:10.3390/ph14010033 · Cited by 74 · see citing works
Iron Pathophysiology in Alzheimer’s Diseases
Wang, T., Xu, S.-F., Fan, Y.-G., Li, L.-B., & Guo, C. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-9589-5_5 · Cited by 64 · see citing works
Jasiecki, J., & Wasąg, B. (2019) · Biomolecules · doi:10.3390/biom9100592 · Cited by 63 · see citing works
In vitro antiamyloidogenic properties of 1,4-naphthoquinones
Bermejo‐Bescós, P., Martín‐Aragón, S., Jiménez‐Aliaga, K., Ortega, A., Molina, M. T., Buxaderas, E., Orellana, G., & Csákÿ, A. G. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.08.038 · Cited by 50 · see citing works
Reviews on 1,4-naphthoquinones fromDiospyrosL.
Nematollahi, A., Aminimoghadamfarouj, N., & Wiart, C. (2012) · Journal of Asian Natural Products Research · doi:10.1080/10286020.2011.633515 · Cited by 49 · see citing works
Neuropharmacological screening of Diospyros mespiliformis in mice
Adzu, B., Amos, S., Muazzam, I., Inyang, U. S., & Gamaniel, K. (2002) · Journal of Ethnopharmacology · doi:10.1016/s0378-8741(02)00249-0 · Cited by 36 · see citing works
Ongoing Research on the Role of Gintonin in the Management of Neurodegenerative Disorders
Ikram, M. A., Ullah, R., Khan, A., & Kim, M. O. (2020) · Cells · doi:10.3390/cells9061464 · Cited by 36 · see citing works
Isomae, K., Ishikawa, M., Ohta, M., Ogawa, Y., Hasegawa, H., Kohda, T., & Kamei, J. (2002) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.88.206 · Cited by 33 · see citing works
Wang, M., Bi, W., Fan, K., Li, T., Yan, T., Xiao, F., He, B., Kai-shun, B., & Jia, Y. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.10.088 · Cited by 29 · see citing works
Tammam, M. A., Sebak, M., Greco, C., Kijjoa, A., & El‐Demerdash, A. (2022) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2022.133711 · Cited by 26 · see citing works
Anti-cancer activities of diospyrin, its derivatives and analogues
Sagar, S., Kaur, M., Minneman, K. P., & Bajić, V. B. (2010) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2010.06.021 · Cited by 25 · see citing works
Molecular docking of Diospyrin as a LOX inhibitory compound
Uddin, G., Rauf, A., Arfan, M., Waliullah, Rehman, T. U., Khan, A. Z., Ali, G., Rehman, B., & Zia‐Ul‐Haq, M. (2013) · Journal of Saudi Chemical Society · doi:10.1016/j.jscs.2013.01.009 · Cited by 18 · see citing works
Mushtaq, A., Anwar, R., & Ahmad, M. (2018) · Tropical Journal of Pharmaceutical Research · doi:10.4314/tjpr.v17i8.11 · Cited by 15 · see citing works
Jeon, S. J., Kim, B., Park, H. J., Zhang, J., Kwon, Y., Kim, D. H., & Ryu, J. H. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.01.040 · Cited by 11 · see citing works
Khelifi, I., Tourrette, A., Dhouafli, Z., Bouajila, J., Efferth, T., Abdelfatah, S., Ksouri, R., & Hayouni, E. A. (2019) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.1870 · Cited by 9 · see citing works
Flagged first, then by citations
4 of the 48 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Ayaz, M., Mosa, O. F., Nawaz, A., Hamdoon, A. A. E., Elkhalifa, M. E. M., Sadiq, A., Ullah, F., Ahmed, A., Kabra, A., Khan, H. Z., et al. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.155272 · Cited by 49 · see citing works
Dong, M., Ming, X., Xiang, T., Feng, N., Zhang, M., Ye, X., He, Y., Zhou, M., & Wu, Q. (2024) · Food & Function · doi:10.1039/d4fo02600d · Cited by 40 · 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
Alghamdi, M. A. (2025) · Pharmaceuticals · doi:10.3390/ph18071041 · Cited by 22 · see citing works
Ekinci, E., Çiftçi, H., Adem, Ş., Aytaç, Ö. G., & Eyüpoğlu, V. (2025) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2025.141734 · Cited by 6 · see citing works
Abduljawad, A. A., Alkinani, K. B., Zaakan, A., AlGhamdi, A. S., Hamdoon, A. A. E., Alshanbari, B. H., Alshehri, A. A., Alluhaybi, B. B., Alqashi, S. O. I., & Abduljawad, R. A. (2025) · Pharmaceuticals · doi:10.3390/ph18111731 · Cited by 6 · see citing works
Ghose, A., Paidesetty, S. K., Prusty, S. K., Satapathy, B. S., Panda, P. K., Pakeeraiah, K., Mishra, A., & Dandela, R. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110242 · Cited by 5 · see citing works
Diospyrin: biosynthesis, distribution in the plant kingdom, and therapeutic potential
Nahar, L., & Sarker, S. D. (2025) · Phytochemistry Reviews · doi:10.1007/s11101-025-10200-y · Cited by 1 · see citing works
Ma, C. J. (2025) · Natural Product Sciences · doi:10.20307/nps.2025.31.1.55
Emerging Drug Candidates from Plants
Das, B., Chaudhary, S. K., Jana, U. K., Ka‐Ot, A. L., Rai, S., Devi, S. I., Bhardwaj, P. K., & Mukherjee, P. K. (2025) · Royal Society of Chemistry eBooks · doi:10.1039/9781837676989-00032
- Authors
- Alam, A., Ali, G., Nawaz, A., AlOmar, T. S., Rauf, A., Ayaz, M., Ahmad, S., Almasoud, N., AlOmar, A. S., Khalil, A. A., & Wilairatana, P.
- Affiliations
- University of Peshawar (PK)
- University of Malakand (PK)
- Princess Nourah bint Abdulrahman University (SA)
- Abasyn University (PK)
- Imam Mohammad ibn Saud Islamic University (SA)
- University of Lahore (PK)
- Mahidol University (TH)
- Corresponding author
- Ali, Gowhar
- Rauf, Abdur
- ORCID
- Venue
- Fitoterapia
- Publisher
- Elsevier BV
- Published
- 2023-12
- Volume
- 171
- Pages
- 105703
- ISSN
- 0367-326X (ISSN-L)
- OpenAlex
- W4387666921
- Cited by
- 9
- References
- 48
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 1 · 2023: 1
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Fitoterapia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Princess Nourah Bint Abdulrahman University (PNURSP-HC2023/5)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- diospyrin, Alzheimer's disease, neuroprotection, acetylcholinesterase inhibition, butyrylcholinesterase inhibition, antioxidant activity, memory impairment, motor function, molecular docking, donepezil
- MeSH terms
- Acetylcholinesterase, Alzheimer Disease, Animals, Antioxidants, Butyrylcholinesterase, Cholinesterase Inhibitors, Naphthoquinones, Molecular Structure, Neuroprotective Agents, Neurodegenerative Diseases, Molecular Docking Simulation
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
