β-Caryophyllene (BCP) ameliorates MPP+ induced cytotoxicity.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases resulting from the continuous death of dopaminergic neurons in substantia nigra. MPP+ (1-methyl-4-phenylpyridinium) has been reported to be a major neurotoxin causing neurotoxic insults on dopaminergic neurons in humans. β-Caryophyllene (BCP), an important cannabinoid derived from the essential oils of different species, has displayed pharmacological properties in different kinds of tissues and cells. However, neuroprotective effects of BCP in PD haven't been reported before. Our results indicate that treatment with MPP+ in SH-SY5Y cells led to a significant decrease in cell viability, which was restored by BCP. Additionally, BCP suppressed MPP+-induced release of lactic dehydrogenase (LDH) and the generation of reactive oxygen species (ROS). In contrast, BCP treatment restored the reduction in mitochondrial membrane potential (MMP) induced by MPP+. BCP treatment increased intracellular GSH and GPx activity. Also, we found that the antioxidant effects of BCP against MPP+- induced neurotoxicity are dependent on cannabinoid receptor type 2 (CB2R). Moreover, our results indicated that BCP prevented MPP+-induced apoptosis of SH-SY5Y through inhibiting the up-regulation of cleaved Caspase-3, Bax, and restoring the expression of Bcl-2. Besides, BCP markedly suppressed HO-1 activation and c-Jun N-terminal Kinase (JNK) phosphorylation. We conclude that BCP might act as a promising therapeutic agent against MPP+ toxicity in neuronal cells.