Canna~Fangled Abstracts

Promising neuroprotective effects of β-caryophyllene against LPS-induced oligodendrocyte toxicity: A mechanistic study.

By December 5, 2018No Comments
2018 Dec 5. pii: S0006-2952(18)30500-8. doi: 10.1016/j.bcp.2018.12.001.
[Epub ahead of print]

Abstract

Myelin loss subsequent to oligodendrocyte death has been reported in a variety of myelin-associated disorders such as multiple sclerosis (MS). Lipopolysaccharide (LPS) has been shown to elicit cellular responses in the central nervous system (CNS) and trigger immune infiltrates and glial cells to release a variety of inflammatory cytokines and mediators. LPS-induced oligodendrocytes toxicity may be chosen as an efficient model to evaluate the role of oligodendrocytes in neuroprotective activities of compounds. β-caryophyllene (BCP) is a selective type 2 cannabinoid (CB2) receptor agonist. However, the mechanisms underlying the anti-inflammatory effects of BCP are not completely understood. On this basis, we aimed to investigate the protective effects of a wide range of BCP concentrations against LPS-induced toxicity in a proliferative oligodendrocyte cell line (OLN-93) and evaluate the possible correlation between BCP concentration and selective modulation of CB2, Nrf2, sphingomyelinase (SMase) and peroxisome proliferator-activated receptors (PPAR)-γ signaling pathways. We found that LPS significantly increases the levels of reactive oxygen species (ROS), nitric oxide (NO) metabolite and tumor necrosis factor (TNF)-α production while decreases the level of GSH. BCP could prevent LPS-induced cytotoxicity and excessive production of NO, ROS, and TNF-α. Also, we demonstrated that BCP’s protective effects against LPS-induced oligodendrocytes toxicity were mediated via the CB2 receptor through different pathways including Nrf2/HO-1/anti-oxidant axis, and PPAR-γ, at low (0.2 and 1µM), and high (10-50µM) concentrations, respectively. Additionally, we observed that the addition of SMase inhibitors imipramine (IMP) and fluoxetine (FLX) synergistically increased the protective effects of BCP. Finally, BCP at low concentrations exerted promising protective effects that could be considered for the treatment of neurodegenerative disorders such as MS. However, more studies using other models of neurodegenerative diseases should be undertaken to assess different parameters such as the activity or expression of SMase.

KEYWORDS:

Cannabinoid receptor; Ceramide; Nrf2/HO–1 axis; Sphingomyelinase; β–caryophyllene

PMID: 30529211
DOI: 10.1016/j.bcp.2018.12.001