IRCCS Centro Neurolesi "Bonino Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy.
Fitoterapia. 2020 Jun;143:104553. doi: 10.1016/j.fitote.2020.104553. Epub 2020 Mar 14.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of the nigrostriatal dopaminergic pathway with loss of substantia nigra pars compacta neurons and dopamine depletion. Various natural compounds showed protective actions against PD. In this work, the protective effects of cannabidiol (CBD), obtained from Cannabis sativa, were evaluated in retinoic acid differentiated SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP), an in vitro PD model. In order to evaluate which receptor is involved in CBD actions CB1, CB2 and TRPV1 receptor antagonists were used. CBD counteracted the loss of cell viability caused by MPP, reducing apoptosis as demonstrated by the reduction of Bax and caspase 3. Moreover, CBD reduced the nuclear levels of PARP-1. The protective effects of CBD seem to be mediated by the activation of ERK and AKT/mTOR pathways. The treatment with AKT1/2 inhibitor and the mTOR inhibitor rapamycin abolished CBD protective effects. The CBD-induced ERK activation may be mediated by CBD interaction with CB2 and TRPV1. We also investigated the protein levels of the autophagic proteins LC3 and beclin 1. CBD reduced the MPP-induced increase of LC3 by CB2 and TRPV1 receptors. These data suggested the involvement of ERK in the modulation of autophagy. However, beclin 1 levels were not modified neither by MPP nor by CBD. These results indicated that CBD may exert preventive and protective actions in PD.
帕金森病（PD）是一种神经退行性疾病，其特征是黑质纹状体多巴胺能通路退化，导致黑质致密部神经元丧失和多巴胺耗竭。各种天然化合物显示出对 PD 的保护作用。在这项工作中，评估了大麻素（CBD）对分化的 SH-SY5Y 细胞暴露于 1-甲基-4-苯基吡啶（MPP）的保护作用，MPP 是体外 PD 模型。为了评估 CBD 作用涉及哪种受体，使用了 CB1、CB2 和 TRPV1 受体拮抗剂。CBD 拮抗 MPP 引起的细胞活力丧失，减少凋亡，如 Bax 和 caspase 3 的减少所证明的那样。此外，CBD 降低了 PARP-1 的核水平。CBD 的保护作用似乎是通过激活 ERK 和 AKT/mTOR 途径介导的。用 AKT1/2 抑制剂和 mTOR 抑制剂 rapamycin 处理可消除 CBD 的保护作用。CBD 诱导的 ERK 激活可能是通过 CBD 与 CB2 和 TRPV1 受体相互作用介导的。我们还研究了自噬蛋白 LC3 和 beclin 1 的蛋白水平。CBD 通过 CB2 和 TRPV1 受体降低了 MPP 诱导的 LC3 增加。这些数据表明 ERK 参与了自噬的调节。然而，MPP 或 CBD 均未改变 beclin 1 水平。这些结果表明 CBD 可能在 PD 中发挥预防和保护作用。
