Department of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, CSIC, Madrid, Spain.
Cell Death Dis. 2012 Jun 28;3(6):e331. doi: 10.1038/cddis.2012.71.
Cannabidiol (CBD) is the most abundant cannabinoid in Cannabis sativa that has no psychoactive properties. CBD has been approved to treat inflammation, pain and spasticity associated with multiple sclerosis (MS), of which demyelination and oligodendrocyte loss are hallmarks. Thus, we investigated the protective effects of CBD against the damage to oligodendrocyte progenitor cells (OPCs) mediated by the immune system. Doses of 1 μM CBD protect OPCs from oxidative stress by decreasing the production of reactive oxygen species. CBD also protects OPCs from apoptosis induced by LPS/IFNγ through the decrease of caspase 3 induction via mechanisms that do not involve CB1, CB2, TRPV1 or PPARγ receptors. Tunicamycin-induced OPC death was attenuated by CBD, suggesting a role of endoplasmic reticulum (ER) stress in the mode of action of CBD. This protection against ER stress-induced apoptosis was associated with reduced phosphorylation of eiF2α, one of the initiators of the ER stress pathway. Indeed, CBD diminished the phosphorylation of PKR and eiF2α induced by LPS/IFNγ. The pro-survival effects of CBD in OPCs were accompanied by decreases in the expression of ER apoptotic effectors (CHOP, Bax and caspase 12), and increased expression of the anti-apoptotic Bcl-2. These findings suggest that attenuation of the ER stress pathway is involved in the 'oligoprotective' effects of CBD during inflammation.
大麻二酚（CBD）是大麻中含量最丰富的大麻素，没有精神活性。CBD 已被批准用于治疗多发性硬化症（MS）相关的炎症、疼痛和痉挛，其中脱髓鞘和少突胶质细胞丢失是标志。因此，我们研究了 CBD 对免疫系统介导的少突胶质前体细胞（OPC）损伤的保护作用。1μM CBD 通过减少活性氧的产生来保护 OPC 免受氧化应激。CBD 还通过不涉及 CB1、CB2、TRPV1 或 PPARγ 受体的机制，通过降低 caspase 3 的诱导来保护 LPS/IFNγ 诱导的 OPC 凋亡。他丁霉素诱导的 OPC 死亡被 CBD 减弱，这表明内质网（ER）应激在 CBD 的作用模式中起作用。这种对 ER 应激诱导的细胞凋亡的保护作用与 eiF2α 的磷酸化减少有关，eiF2α 是 ER 应激途径的启动子之一。事实上，CBD 减弱了 LPS/IFNγ 诱导的 PKR 和 eiF2α 的磷酸化。CBD 在 OPCs 中的促生存作用伴随着 ER 凋亡效应物（CHOP、Bax 和 caspase 12）的表达减少，以及抗凋亡 Bcl-2 的表达增加。这些发现表明，在炎症过程中，衰减 ER 应激途径参与了 CBD 的“少突胶质保护”作用。
