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

Background: Phytocannabinoids (pCBs) have been shown to inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer's disease protein beta amyloid (Aβ). We characterized the capacity of six pCBs-cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), cannabidivarin (CBDV), cannabidiol (CBD) and Δ -tetrahydrocannabinol (Δ -THC)-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.

The semi-synthetic flavonoid 2',3',4'-trihydroxyflavone (2-D08) inhibits both SN-38- and cytokine-evoked increases in epithelial barrier permeability in an intestinal mucositis model.

The chemotherapeutic drug irinotecan and its active metabolite SN-38 have been linked to the development of off-target gastrointestinal toxicity and inflammation, termed gastrointestinal mucositis (GIM). Flavonoids possess antioxidant and anti-inflammatory effects in models of gastrointestinal inflammation; however, few studies have investigated their potential in ameliorating chemotherapy-induced GIM. Here, we characterised the intestinal epithelial barrier-protective and antioxidant capacity of the novel flavonoids 2',3',4'-trihydroxyflavone (2-D08) and transilitin in comparison with flavones myricetin and quercetin viability and permeability assessments in Caco-2 epithelial monolayers exposed to 7-ethyl-10-hydroxycamptothecin (SN-38).

Structure-activity relationships for flavone interactions with amyloid β reveal a novel anti-aggregatory and neuroprotective effect of 2',3',4'-trihydroxyflavone (2-D08).

Naturally-occurring flavonoids have well documented anti-aggregatory and neuroprotective properties against the hallmark toxic protein in Alzheimer's disease, amyloid β (Aβ). However the extensive diversity of flavonoids has limited the insight into the precise structure-activity relationships that confer such bioactive properties against the Aβ protein. In the present study we have characterised the Aβ binding properties, anti-aggregatory and neuroprotective effects of a discreet set of flavones, including the recently described novel protein sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08).