Neuroprotective effect of cannabidiol, a non‐psychoactive component from Cannabis sativa, on β‐amyloid‐induced toxicity in PC12 cells

Iuvone, Teresa; Esposito, Giuseppe; Esposito, Ramona; Santamaria, Rita; Di Rosa, Massimo; Izzo, Angelo A.

doi:10.1111/j.1471-4159.2003.02327.x

Cited by 361Alzheimer's disease research and treatmentsCannabis and Cannabinoid ResearchMedicinal Plants and Neuroprotection

Neuroprotective effect of cannabidiol, a non‐psychoactive component from Cannabis sativa, on β‐amyloid‐induced toxicity in PC12 cells

Iuvone, Teresa, Esposito, Giuseppe, Esposito, Ramona, Santamaria, Rita, Di Rosa, Massimo, Izzo, Angelo A.·2004·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2003.02327.x

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Abstract

Abstract Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of beta-amyloid peptide aggregates. Here, we studied the effect of cannabidiol, a major non-psychoactive component of the marijuana plant (Cannabis sativa) on beta-amyloid peptide-induced toxicity in cultured rat pheocromocytoma PC12 cells. Following exposure of cells to beta-amyloid peptide (1 micro g/mL), a marked reduction in cell survival was observed. This effect was associated with increased reactive oxygen species (ROS) production and lipid peroxidation, as well as caspase 3 (a key enzyme in the apoptosis cell-signalling cascade) appearance, DNA fragmentation and increased intracellular calcium. Treatment of the cells with cannabidiol (10(-7)-10(-4)m) prior to beta-amyloid peptide exposure significantly elevated cell survival while it decreased ROS production, lipid peroxidation, caspase 3 levels, DNA fragmentation and intracellular calcium. Our results indicate that cannabidiol exerts a combination of neuroprotective, anti-oxidative and anti-apoptotic effects against beta-amyloid peptide toxicity, and that inhibition of caspase 3 appearance from its inactive precursor, pro-caspase 3, by cannabidiol is involved in the signalling pathway for this neuroprotection.

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In PC12 neuronal cells, CBD has shown protection against oxidative stress and Aβ-induced neurotoxicity.
“In PC12 neuronal cells, CBD has shown protection against oxidative stress, Aβ-induced neurotoxicity, inhibition of tau hyperphosphorylation, prevention of proinflammatory gene transcription, and inhibition of Aβ-induced tau hyperphosphorylation [188,189].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [189]
In PC12 neuronal cells, CBD has shown inhibition of tau hyperphosphorylation.
“In PC12 neuronal cells, CBD has shown protection against oxidative stress, Aβ-induced neurotoxicity, inhibition of tau hyperphosphorylation, prevention of proinflammatory gene transcription, and inhibition of Aβ-induced tau hyperphosphorylation [188,189].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [189]
In PC12 neuronal cells, CBD has shown prevention of proinflammatory gene transcription.
“In PC12 neuronal cells, CBD has shown protection against oxidative stress, Aβ-induced neurotoxicity, inhibition of tau hyperphosphorylation, prevention of proinflammatory gene transcription, and inhibition of Aβ-induced tau hyperphosphorylation [188,189].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [189]

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Background

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Authors: Iuvone, T., Esposito, G., Esposito, R., Santamaria, R., Di Rosa, M., & Izzo, A. A.
Affiliations: University of Naples Federico II (IT)
Corresponding author: Esposito, Giuseppe
Izzo, Angelo A.
ORCID: Esposito, Giuseppe
Santamaria, Rita
Izzo, Angelo A.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2004-03-10
Volume: 89
Issue: 1
Pages: 134-141
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/j.1471-4159.2003.02327.x
OpenAlex: W2070616859
Cited by: 361
References: 60
Citations by year: 2026: 14 · 2025: 17 · 2024: 28 · 2023: 21 · 2022: 27 · 2021: 18 · 2020: 23 · 2019: 19 · 2018: 22 · 2017: 16 · 2016: 12 · 2015: 7 · 2014: 10 · 2013: 14 · 2012: 14
FWCI: 12.16
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Funders: Sanofi
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Keywords: cannabidiol, beta-amyloid peptide, neuroprotection, Alzheimer's disease, PC12 cells, oxidative stress, reactive oxygen species, lipid peroxidation, caspase-3, apoptosis, DNA fragmentation, intracellular calcium, Cannabis sativa
MeSH terms: Animals, Calcium, Cannabidiol, Cannabis, Cell Membrane, Cell Survival, Dose-Response Relationship, Drug, Intracellular Fluid, Neurons, Peptide Fragments, Lipid Peroxidation, Amyloid beta-Peptides, PC12 Cells, Apoptosis, Reactive Oxygen Species, Neuroprotective Agents, Caspases, Rats, Caspase 3, DNA Fragmentation

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Neuroprotective effect of cannabidiol, a non‐psychoactive component from Cannabis sativa, on β‐amyloid‐induced toxicity in PC12 cells

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