Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Life Sci. 2019 Feb 15;219:40-73. doi: 10.1016/j.lfs.2018.12.059. Epub 2019 Jan 5.
Neuroinflammation is observed as a routine characterization of neurodegenerative disorders such as dementia, multiple sclerosis (MS) and Alzheimer's diseases (AD). Scientific evidence propounds both of the neuromodulatory and immunomodulatory effects of CB in the immune system. β-Caryophyllene (BCP) is a dietary selective CB agonist, which deserves the anti-inflammatory and antioxidant effects at both low and high doses through activation of the CB receptor.
In this study, we investigated the protective effects of a broad range concentration of BCP against LPS-induced primary microglia cells inflammation and M/M imbalance and identifying the portion of the involvement of related signaling pathways on BCP effects using pharmacological antagonists of CB, PPAR-γ, and sphingomyelinase (SMase).
The protective effects of BCP on LPS-induced microglia imbalance is provided by the M healing phenotype of microglia, releasing the anti-inflammatory (IL-10, Arg-1, and urea) and anti-oxidant (GSH) parameters and reducing the inflammatory (IL-1β, TNF-α, PGE, iNOS and NO) and oxidative (ROS) biomarkers. Moreover, we showed that BCP exerts its effects through CB receptors which overproduction of ceramides by SMase at middle to higher concentrations of BCP reduce the protective activity of BCP and results in the activation of the PPAR-γ pathway.
In conclusion, the low concentration of BCP has higher selective anti-inflammatory effects rather than high levels. On this occasion, BCP by modulating the microglia is able to have potential therapeutic effects in neuro-inflammation conditions and microglia cells such as MS and AD.
神经炎症是痴呆症、多发性硬化症（MS）和阿尔茨海默病（AD）等神经退行性疾病的常规特征。科学证据表明，大麻素在免疫系统中具有神经调节和免疫调节作用。β-石竹烯（BCP）是一种饮食性选择性大麻素受体激动剂，通过激活大麻素受体，在低剂量和高剂量下都具有抗炎和抗氧化作用。
在这项研究中，我们研究了广泛浓度的 BCP 对 LPS 诱导的原代小胶质细胞炎症和 M/M 失衡的保护作用，并使用大麻素受体、过氧化物酶体增殖物激活受体-γ（PPAR-γ）和神经鞘磷脂酶（SMase）的药理学拮抗剂来确定相关信号通路对 BCP 作用的参与部分。
BCP 通过小胶质细胞的 M 修复表型对 LPS 诱导的小胶质细胞失衡提供保护作用，释放抗炎（IL-10、Arg-1 和尿素）和抗氧化（GSH）参数，并降低炎症（IL-1β、TNF-α、PGE、iNOS 和 NO）和氧化（ROS）生物标志物。此外，我们表明，BCP 通过大麻素受体发挥作用，在较高浓度的 BCP 中，SMase 产生的神经酰胺会导致 BCP 的保护活性降低，并激活 PPAR-γ 通路。
总之，BCP 的低浓度具有更高的选择性抗炎作用，而不是高浓度。在这种情况下，BCP 通过调节小胶质细胞，在 MS 和 AD 等神经炎症和小胶质细胞条件下具有潜在的治疗作用。
