“Neuroinflammation and oxidative stress are recognized as key drivers of neuronal death and the progression of neurodegenerative diseases. At the same time, they serve as central hubs linking the major pathological hallmarks of Alzheimer’s disease (AD), including Aβ aggregation, tau protein hyperphosphorylation, neurofibrillary tangle formation, and neuronal injury.
In this study, we screened natural active molecules of cannabidiol (CBD) and its derivatives, and conducted molecular docking simulations. A class of CBD aminoquinone scaffolds with potential anti-AD activity was identified, and 32 CBD aminoquinone derivatives were synthesized for comprehensive in vitro and in vivo evaluation.
Among them, compound G-12 with p-F-aniline moiety exhibited potent anti-inflammatory activity (IC50 = 1.39 μM), outstanding neuroprotective effects (IC50 = 1.29 μM), and prominent behavioral manifestations. In addition, G-12 displayed acceptable in vivo pharmacokinetic (PK) properties. The superior performance of G-12 indicated that through the Nrf2/HO-1 oxidative stress pathway, it affected the TLR4/NF-κB inflammatory pathway, inhibited neuroinflammation, and thereby influenced Aβ aggregation, protecting neurons.
This strategy that links several major pathological features of AD is effective in combating AD.
G-12 is also a lead compound with the potential to be developed into a multifunctional drug for AD.”
https://pubmed.ncbi.nlm.nih.gov/41643512
“Cannabidiol (CBD) is one of non-psychoactive cannabinoids derived from cannabis plants. CBD and its structural analogues modulate a broad spectrum of pharmacological targets, including multiple orphan receptors, GPCRs, 5-HT1A receptors, and PPARγ and TRPV1 channels, thus show potential therapeutic effects such as neuroprotection, anti-epilepsy, anti-inflammation, antioxidation. CBD exhibits neuroprotective properties through multiple mechanisms in the treatment of neurodegenerative disorders, including AD, multiple sclerosis, epilepsy, Parkinson’s disease. Currently, CBD has been approved as an orphan drug by the FDA for the treatment of Lennox-Gastaut syndrome and Dravet.”
https://www.sciencedirect.com/science/article/abs/pii/S0045206826001264?via%3Dihub