Cannabidiol protects against Alzheimer's disease in C. elegans via ROS scavenging activity of its phenolic hydroxyl groups.

Abstract

Recent discoveries have implicated the potential of Cannabidiol (CBD) in the prevention of Alzheimer's disease (AD). However, how CBD affects such neurodegenerative disorders remains unclear. Herein, Caenorhabditis elegans (C. elegans) was used as the model organism to elucidate the mechanism by which CBD ameliorates AD in vivo. CBD was found to alleviate the progression of Aβ-induced AD but not tau protein-induced AD or α-syn-induced Parkinson's disease. CBD inhibited the aggregation of Aβ in C. elegans. However, CBD failed to prevent the formation of β-sheet aggregation in vitro. Moreover, CBD was found to scavenge reactive oxygen species (ROS) in vivo without inducing the overexpression of antioxidative genes. In addition, CBD treatment enhanced the worm resistance to oxidative stress, which was independent of the classical transcription factors DAF-16 and SKN-1. These results supported that the in vivo antioxidative activity of CBD was most likely due to its intrinsic antioxidative property. Furthermore, the phenolic hydroxyl groups of CBD were found to be critical for scavenging ROS in vitro and in vivo, alleviating the aggregation of Aβ in vivo, and ameliorating Aβ-associated neurotoxicity. These studies show that CBD protects against AD in C. elegans via the ROS scavenging activity of its phenolic hydroxyl groups, which provides insight for further structure-activity relationship studies of CBD as an AD therapeutic.

• Authors: Yue Zhang, Hongyuan Li, Sha Jin, Yuyuan Lu, Yinghua Peng, Lihui Zhao, Xiaohui Wang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 919 Pg. 174829 (Mar 15 2022) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 35181336 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Free Radical Scavengers
• Reactive Oxygen Species
• Cannabidiol

Topics

• Alzheimer Disease (drug therapy)
• Animals
• Caenorhabditis elegans (drug effects)
• Cannabidiol (chemistry, pharmacology, therapeutic use)
• Free Radical Scavengers (chemistry, pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Structure-Activity Relationship