Beta-caryophyllene inhibits the permeability of the blood-brain barrier in MPTP-induced parkinsonism

Introduction: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Although the precise pathogenesis of PD remains unclear, several studies demonstrate that oxidative stress, inflammation, low levels of antioxidants, and the presence of biomolecules that generate reactive oxygen species can disrupt the blood-brain barrier (BBB) as an essential feature of the disease. Aims: This study aimed to test whether agonism to cannabinoid receptor type 2 (CB2) through the administration of (3-caryophyllene (BCP) could correct BBB permeability in the 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonism induction model. Methods: We conducted a molecular assessment of proteins (immunochemistry and western blot), BBB permeability, and related biomarkers of PD (lipid peroxidation) in the MPTP mouse model of the disease. Results: Expression of zonula occludens (ZO-1) and occludin tight junction (TJ) proteins was dampened in the striatum and substantia nigra pars compacta of mice, while lipid peroxidation and BBB permeability increased in the striatum in the MPTP-treated group, and these effects were reversed under BCP administration. This phytocannabinoid was able to restore protein expression and immunoreactivity of tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP), as well as nuclear factor-erythroid 2-related factor (NRF2) translocation to the nucleus, and NADPH quinone oxidase 1 (NQO1) expression in mice treated with MPTP.