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Natural compounds as multitarget agents in Alzheimer's diseases: evidence from in vivo and in vitro models
Suswidiantoro V, Tang KS, Rahman K, Ariestanti DM, James RJ, Yan CC, Kato M, Saputri FC.. Frontiers in pharmacology, 2026-02-23
Topic: Amyloid, tau and blood-test diagnosis
Introduction Alzheimer's disease (AD), the most common cause of dementia, is marked by a gradual decline in cognitive function driven by amyloid-β (Aβ) deposition, tau hyperphosphorylation, synaptic failure, neuroinflammatory responses, and mitochondrial dysfunction. Despite extensive research efforts, currently available pharmacological treatments provide only limited symptomatic relief and do not prevent disease progression. These shortcomings have fuelled growing interest in natural compounds, which possess pleiotropic biological properties and may more effectively target the multifaceted pathology of AD. Methods This systematic review was performed in compliance with the PRISMA 2020 guidelines. Comprehensive literature searches were conducted across PubMed, Scopus, and ScienceDirect to identify preclinical and clinical studies examining the effects of natural compounds in in vitro and in vivo models relevant to AD. Eligible studies assessed phytochemicals, herbal formulations, marine-derived substances, or nutraceuticals and their impact on core AD-related pathological features. Results A total of 41 studies fulfilled the inclusion criteria, including 25 in vivo and 16 in vitro investigations. Across these studies, natural compounds consistently exhibited neuroprotective effects via multiple mechanisms associated with AD pathogenesis. These included the reduction of oxidative stress and neuroinflammation, inhibition of apoptotic pathways, modulation of amyloidogenic processes, attenuation of Aβ aggregation, regulation of tau-associated signalling, and preservation of synaptic function and cognitive outcomes. Conclusion Overall, the available evidence suggests that natural compounds confer multitarget neuroprotective effects that directly engage with key pathological mechanisms underlying AD. Nonetheless, significant translational challenges remain, particularly with respect to bioavailability, compound standardisation, and clinical efficacy. Further robust, well-controlled clinical trials are essential to establish the therapeutic value of these agents as potential disease-modifying interventions for AD.
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APA 7th
Suswidiantoro, V., Tang, K. S., Rahman, K., Ariestanti, D. M., James, R. J., Yan, C. C., et al. (2026). Natural compounds as multitarget agents in Alzheimer's diseases: evidence from in vivo and in vitro models. Frontiers in pharmacology. https://doi.org/10.3389/fphar.2026.1766470
Vancouver
Suswidiantoro V, Tang KS, Rahman K, Ariestanti DM, James RJ, Yan CC, et al. Natural compounds as multitarget agents in Alzheimer's diseases: evidence from in vivo and in vitro models. Frontiers in pharmacology. 2026. doi:10.3389/fphar.2026.1766470. PMID: 41808871.
BibTeX
@article{suswidiantoro2026-41808871,
author = {Suswidiantoro, V. and Tang, K. S. and Rahman, K. and Ariestanti, D. M. and James, R. J. and Yan, C. C. and Kato, M. and Saputri, F. C.},
title = {{Natural compounds as multitarget agents in Alzheimer's diseases: evidence from in vivo and in vitro models}},
journal = {Frontiers in pharmacology},
year = {2026},
doi = {10.3389/fphar.2026.1766470},
pmid = {41808871},
url = {https://doi.org/10.3389/fphar.2026.1766470}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Results A total of 41 studies fulfilled the inclusion criteria, including 25 in vivo and 16 in vitro investigations.
- Across these studies, natural compounds consistently exhibited neuroprotective effects via multiple mechanisms associated with AD pathogenesis.
- Conclusion Overall, the available evidence suggests that natural compounds confer multitarget neuroprotective effects that directly engage with key pathological mechanisms underlying AD.
- Nonetheless, significant translational challenges remain, particularly with respect to bioavailability, compound standardisation, and clinical efficacy.
Why it matters
This systematic review of 41 lab studies, 25 in animals and 16 in cells, found that natural compounds such as plant chemicals and herbal formulas consistently showed protective effects against Alzheimer's-related changes, including less oxidative stress, inflammation and amyloid-β clumping. The authors note that problems with absorption, standardization and proof of clinical benefit remain, and that well-controlled clinical trials are needed before these can be considered treatments.
Study details
- Study designsystematic review
- Participants41
- Evidence strengthHigh
How this study scored 59/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in pharmacology) |
| Journal's citation record | 2 / 4 | Frontiers in Pharmacology: journal h-index 242 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 1 / 4 | 41 participants |
| 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 | A review of other studies — randomisation is not credited here |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 29.1× 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 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Fadlina Chany Saputri: h-index 19 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Tsukuba: institution h-index 685 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41808871) |
| Free to read | 2 / 2 | Free to read |
| Total | 59 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fphar.2026.1766470
- PubMed: 41808871
- Original source →
- Free full text: Frontiers in Pharmacology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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