Characterization of Orange Peel Extract and Its Potential Protective Effect against Aluminum Chloride-Induced Alzheimer’s Disease
Open accessAbstract
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder without a cure. Hence, developing an effective treatment or protective agent is crucial for public health. The present study aims to characterize orange peel extract (OPE) through in vitro and in silico studies. Furthermore, it examines the protective effect of OPE against experimentally-induced Alzheimer’s disease in rats. The total phenolic and flavonoid content of OPE was 255.86 ± 1.77 and 52.06 ± 1.74 (mg/100 g), respectively. Gallic acid, the common polyphenol in OPE detected by HPLC was 3388.60 μg/100 g. OPE antioxidant IC50 was 67.90 ± 1.05, 60.48 ± 0.91, and 63.70 ± 0.30 by DPPH, ABTS and Hydroxyl radical scavenging activity methods, respectively. In vitro anti-acetylcholinesterase (AChE) IC50 was 0.87 ± 0.025 mg/mL for OPE and 2.45 ± 0.001 mg/mL for gallic acid. Molecular docking analysis for human AChE (4EY7) with donepezil, gallic acid, and acetylcholine showed binding energy ΔG values of −9.47, −3.72, and −5.69 Kcal/mol, respectively. Aluminum chloride injection (70 mg/Kg/day for 6 weeks) induced Alzheimer’s-like disease in male rats. OPE (100 and 200 mg/kg/d) and gallic acid (50 mg/kg/d) were administered orally to experimental animals for 6 weeks in addition to aluminum chloride injection (as protective). OPE was found to protect against aluminum chloride-induced neuronal damage by decreasing both gene expression and activity of acetylcholinesterase (AChE) and a decrease in amyloid beta (Aβ42) protein level, thiobarbituric acid-reactive substances (TBARS), and nitric oxide (NO), and increased reduced glutathione (GSH) level and activity of the antioxidant enzymes in the brain tissues. Additionally, gene expressions for amyloid precursor protein (APP) and beta secretase enzyme (BACE1) were downregulated, whereas those for presinilin-2 (PSEN2) and beta cell lymphoma-2 (BCL2) were upregulated. Furthermore, the reverse of mitochondrial alternation and restored brain ultrastructure might underlie neuronal dysfunction in AD. In conclusion, our exploration of the neuroprotective effect of OPE in vivo reveals that OPE may be helpful in ameliorating brain oxidative stress, hence protecting from Alzheimer’s disease progression.
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Orange peel extract (100-200 mg/kg) significantly decreased AChE activity and mRNA expression and protected brain tissue by decreasing oxidative stress in AlCl3-treated rats.
“Orange peel extract (100–200 mg/kg) also significantly decreased AChE activity and mRNA expression and protected brain tissue by decreasing oxidative stress in AlCl3-treated rats [69].”
From Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review (2025) · cites this paper as [69]
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RETRACTED ARTICLE: Aluminum in Neurological and Neurodegenerative Disease
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Abdel‐Salam, O. M. E., El-Shamarka, M. E.-S., Youness, E. R., et al. (2021) · PubMed · doi:10.22038/ijbms.2021.58246.12940 · Cited by 11 · see citing works
Hirai, M., Ajito, S., Sato, S., Ohta, N., Igarashi, N., & Shimizu, N. (2018) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.8b08006 · Cited by 9 · see citing works
Alzheimer prevention hopes continue to dim
Mullard, A. (2020) · Nature Reviews Drug Discovery · doi:10.1038/d41573-020-00044-w · Cited by 9 · see citing works
Inneh, C., & Eiya, B. O. (2022) · The FASEB Journal · doi:10.1096/fasebj.2022.36.s1.0r755 · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [2]Alzheimer’s Association Alzheimer’s disease facts and figures Alzheimer’s Dement. 2021 17 327 406 33756057
- [81]Elena A. Asier R. Maria V.S. Estibaliz C. Calos M. Chapter 14—Polyphenols attenuate mitochondrial dysfunction induced by amyloid peptides Mitochondrial Physiology and Vegetal Molecules Academic Press Cambridge, MA, USA 2021 317 337
- [108]Kotz S. Balakrishnan N. Read C.B. Vidakovic B. Encyclopedia of Statistical Sciences 2nd ed. Wiley-Interscience Hoboken, NJ, USA 2006 978-0-471-15044-2-9686
Cited by
Sorted by citations
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
- Authors
- Abd El-Aziz, N. M. A., Shehata, M. G., Alsulami, T., Badr, A. N., Elbakatoshy, M. R., Ali, H. S., & El-Sohaimy, S. A.
- Affiliations
- Department of Food Technology, Arid Lands Cultivation Research Institute (ALCRI), City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt
- City of Scientific Research and Technological Applications (EG)
- King Saud University (SA)
- National Research Centre (EG)
- Venue
- Pharmaceuticals
- Publisher
- MDPI AG
- Published
- 2022-12-22
- Volume
- 16
- Issue
- 1
- Pages
- 12
- ISSN
- 1424-8247 (ISSN-L)
- PMC
- PMC9864618
- OpenAlex
- W4312173395
- Cited by
- 31
- References
- 100
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 9 · 2023: 4
- FWCI
- 6.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmaceuticals (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- King Saud University, Riyadh, Saudi Arabia (RSPD2023R641)
- 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 › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- orange peel extract, Alzheimer's disease, aluminum chloride-induced neurotoxicity, acetylcholinesterase inhibition, gallic acid, antioxidant activity, amyloid-beta 42, amyloid precursor protein, beta-secretase, presenilin 2, neuroprotection, oxidative stress, neuroinflammation, neurodegeneration, phenolic compounds, flavonoids, molecular docking
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 ›
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