The structurally diverse phytocannabinoids cannabichromene, cannabigerol and cannabinol significantly inhibit amyloid β-evoked neurotoxicity and changes in cell morphology in PC12 cells

Authors

Dylan T. MarshAyato SugiyamaYuta ImaiRyuji KatoScott D. Smid


Published

September 11, 2023

Abstract

Background

Phytocannabinoids have been shown to inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer’s disease protein beta amyloid (Aβ). We characterised the capacity of six phytocannabinoids: cannabichromene, cannabigerol, cannabinol, cannabidivarin, cannabidiol and Δ9-tetrahydrocannabinol, to disrupt Aβ aggregation and protect against Aβ-evoked neurotoxicity in PC12 cells.

Methods

Neuroprotection against lipid peroxidation and Aβ-induced cytotoxicity was assessed using the MTT assay. Transmission electron microscopy was used to visualise phytocannabinoid effects on Aβ aggregation and fluorescence microscopy, with morphometrics and principal component analysis to assess PC12 cell morphology.

Results

Cannabidiol inhibited lipid peroxidation with no significant effect on Aβ toxicity, while cannabinol, cannabidivarin and cannabigerol provided neuroprotection. Cannabichromene, cannabigerol and cannabinol inhibited Aβ1-42-induced neurotoxicity in PC12 cells, as did Δ9-tetrahydrocannabinol, cannabidiol and cannabidivarin. Cannabichromene, cannabinol and cannabidivarin inhibited Aβ aggregation, while Δ9-tetrahydrocannabinol reduced aggregate density. Aβ1-42 induced morphological changes in PC12 cells, including a reduction in neuritic projections and rounded cell morphology. Cannabichromene and cannabigerol inhibited this effect, while Δ9-tetrahydrocannabinol, cannabidiol and cannabidivarin did not alter Aβ1-42 effects on cell morphology.

Conclusions

These findings highlight the neuroprotective activity of cannabichromene, cannabigerol and cannabinol as novel phytocannabinoids associated with variable effects on Aβ-evoked neurite damage and inhibition of amyloid β aggregation.


DOI: 10.1111/bcpt.13943

Citations

Marsh, D. T., Sugiyama, A., Imai, Y., Kato, R., & Smid, S. D. (2023). The structurally diverse phytocannabinoids cannabichromene, cannabigerol and cannabinol significantly inhibit amyloid β‐evoked neurotoxicity and changes in cell morphology in PC12 cells. Basic & Clinical Pharmacology & Toxicology.