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Alkaloids from Caliphruria subedentata (Amaryllidaceae) as Regulators of AChE, BuChE, NMDA and GSK3 Activity: An In Vitro and In Silico Approach for Mimicking Alzheimer´s Disease
Willian Orlando Castillo Ordoñez, Nilza Velasco Palomino, Patricia Eugenia Vélez Varela, Indeara Martinez, Levy Bueno Alves, Silvana Giuliatti. Neurochemical Research, 2025-03-08
Topic: Brain proteins, microglia and lab models
Patients with Alzheimer's disease (AD) have two types of abnormal protein buildups: amyloid plaques and neurofibrillary tangles, in addition to the early synaptic dysfunction associated with the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Impairment of the glutamatergic system is also crucial for neuronal survival, as it can cause synaptic dysfunction that overstimulates glutamate receptors, especially N-methyl-d-aspartate receptors (NMDARs). Another protein affecting neuronal health is glycogen synthase kinase-3 (GSK3), a widely preserved serine/threonine protein kinase linked to neuronal disorders, including AD. In recent years, alkaloids from the Amaryllidaceae have received great attention for their known anticholinergic activity, as well as their antioxidant, antigenotoxic, and neuroprotective properties. In this context, the identification of compounds capable of interacting with different targets involved in AD provides a possible new therapeutic strategy. In this study, we conducted a combination of in vitro and in silico approaches to identify the potential of C. subedentata in regulating key proteins involved in AD. Viability and neuroprotection assays were performed to evaluate the neuroprotection exerted by C. subedentata extract against neurotoxicity induced by Aβ (1-42) peptide and Okadaic acid in SH-SY5Y cells. Computational methods such as docking and molecular dynamic and viability therapeutic analysis were conducted to explore the interaction of alkaloids from C. subedentata with target proteins (AChE, BuChE, NMDA, and GSK-3) involved in AD. Our findings show that C. subedentata extract exerts neuroprotective effects against neurotoxic stimuli induced by Aβ (1-42) peptide and Okadaic acid. In addition, in silico approaches provide insight into how C. subedentata extract alkaloids interact with key proteins involved in AD. These findings provide insights into the potential therapeutic effects and action mechanisms of these alkaloids. We hope these rapid findings can contribute as a bridge to the identification of new molecules with the potential to counteract the effects of AD.
Key findings
- Patients with Alzheimer's disease (AD) have two types of abnormal protein buildups: amyloid plaques and neurofibrillary tangles, in addition to the early synaptic dysfunction associated with the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE).
- Our findings show that C. subedentata extract exerts neuroprotective effects against neurotoxic stimuli induced by Aβ (1-42) peptide and Okadaic acid.
- These findings provide insights into the potential therapeutic effects and action mechanisms of these alkaloids.
Why it matters
In cell experiments, an extract of the plant Caliphruria subedentata protected SH-SY5Y cells against damage caused by Aβ (1-42) peptide and Okadaic acid, and computational work suggested it interacts with AChE, BuChE, NMDA and GSK3. These are in vitro and in silico findings only, so no conclusion can be drawn about treating or preventing Alzheimer's disease in people.
Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurochemical Research) |
| Journal's citation record | 2 / 4 | Neurochemical Research: journal h-index 163 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “in vitro”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 6 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 3.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Silvana Giuliatti: h-index 20 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Universidade de São Paulo: institution h-index 936 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40056267) |
| Free to read | 2 / 2 | Free to read |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1007/s11064-025-04354-6
- PubMed: 40056267
- Original source →
- Free full text: Neurochemical Research →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Ordoñez, W. O. C., Palomino, N. V., Varela, P. E. V., Martinez, I., Alves, L. B., & Giuliatti, S. (2025). Alkaloids from Caliphruria subedentata (Amaryllidaceae) as Regulators of AChE, BuChE, NMDA and GSK3 Activity: An In Vitro and In Silico Approach for Mimicking Alzheimer´s Disease. Neurochemical Research. https://doi.org/10.1007/s11064-025-04354-6
Vancouver
Ordoñez WOC, Palomino NV, Varela PEV, Martinez I, Alves LB, Giuliatti S. Alkaloids from Caliphruria subedentata (Amaryllidaceae) as Regulators of AChE, BuChE, NMDA and GSK3 Activity: An In Vitro and In Silico Approach for Mimicking Alzheimer´s Disease. Neurochemical Research. 2025. doi:10.1007/s11064-025-04354-6. PMID: 40056267.
BibTeX
@article{ordonez2025-40056267,
author = {Ordoñez, Willian Orlando Castillo and Palomino, Nilza Velasco and Varela, Patricia Eugenia Vélez and Martinez, Indeara and Alves, Levy Bueno and Giuliatti, Silvana},
title = {{Alkaloids from Caliphruria subedentata (Amaryllidaceae) as Regulators of AChE, BuChE, NMDA and GSK3 Activity: An In Vitro and In Silico Approach for Mimicking Alzheimer´s Disease}},
journal = {Neurochemical Research},
year = {2025},
doi = {10.1007/s11064-025-04354-6},
pmid = {40056267},
url = {https://doi.org/10.1007/s11064-025-04354-6}
}
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