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Cannabis sativa extracts reduce inclusion formation in a cell model of alpha-synuclein aggregation

Lookup NU author(s): Professor Tiago OuteiroORCiD

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Abstract

© 2025 Elsevier B.V.Parkinson's disease (PD) is classified as a synucleinopathy due to the accumulation of protein inclusions rich in the alpha-synuclein (aSyn) protein. Identifying effective pharmacological therapies is important to slow the progression and minimize the symptoms of these diseases. Cannabis sativa has a diverse chemical profile depending on its genotype, including several classes of substances, such as cannabinoids, flavonoids, terpenes, and alkaloids. In this study, we evaluated the effects of four C. sativa extracts with different phytocannabinoid chemical profiles in two cellular models that reproduce alterations in cellular homeostasis common during the cellular phase of PD and other synucleinopathies. We used Saccharomyces cerevisiae strains transformed with plasmid DNA and genetically modified human cells (H4), both expressing aSyn. The results showed that all the extracts were antioxidants, decreasing intracellular oxidation levels and increasing the number of daughter cells in yeast cells, but did not prevent mitochondrial damage. Besides, the extracts reduced the number of intracellular inclusions in H4 cells and increased the number of cells without inclusions. Phytochemical characterization revealed extracts rich in Tetrahydrocannabinol – THC (69.88 %), Cannabidiol - CBD (52.64 %), and Cannabinol - CBN (47.38 % and 58.64 %), and we concluded that, regardless of these percentages, all C. sativa extracts showed protective biological activity against toxicity caused by alpha-synuclein production, both in yeast cells and H4 cells.

Publication metadata

Author(s): de Almeida Cruz T, de Paulo Osorio R, de Menezes Epifanio NM, Merghani M, Pereira MD, de Almeida Chaves DS, Outeiro TF, Riger CJ

Publication type: Article

Publication status: Published

Journal: Fitoterapia

Year: 2026

Volume: 188

Print publication date: 01/01/2026

Online publication date: 02/11/2025

Acceptance date: 31/10/2025

ISSN (print): 0367-326X

ISSN (electronic): 1873-6971

Publisher: Elsevier B.V.

URL: https://doi.org/10.1016/j.fitote.2025.106968

DOI: 10.1016/j.fitote.2025.106968

PubMed id: 41187864

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