BACKGROUND Rhodiola rosea L. (Crassulaceae) has been used for years in the traditional medicine of several countries as an adaptogen drug, able to preserve homeostasis in response to stress stimuli. Currently R. rosea roots and rhizome are classified as a traditional herbal medicinal product for temporary relief of symptoms of stress, such as fatigue and sensation of weakness by the European Medicines Agency. HYPOTHESIS/PURPOSE Increasing evidences suggest the involvement of neuroinflammation in response to stress. However, whether the modulation of neuroinflammatory parameters could be involved in the anti-stress effect of R. rosea has been barely studied. Thus, the aim of this work is to investigate the possible modulation of molecular inflammatory processes elicited by a R. rosea roots and rhizome ethanolic extract in an in vitro model of corticotropin releasing hormone (CRH)-stimulated BV2 microglial cells. METHODS BV2 cells were stimulated with CRH 100 nM and changes in cell viability, cytokines production and heat shock protein 70 (HSP70) levels were evaluated. Intracellular pathways related to inflammation, such as nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) nuclear translocation and mitogen-activated protein kinases (MAPK) activation were also analyzed. RESULTS We found that R. rosea extract (2.7% m/m rosavin and 1% m/m salidroside) 20 µg/ml was able to counteract the neuroinflammatory effect of CRH by inhibiting NF-κB nuclear translocation with a mechanism of action involving the modulation of mitogen-activated protein kinase-activated protein kinase 2 (MKK2), extracellular signal-regulated kinase 1/2 (ERK 1/2) and c-Jun n-terminal kinase (JNK), resulting in a reduction of HSP70 expression. CONCLUSION This work expands the knowledge of the intracellular mechanisms involved in R. rosea anti-stress activity and may be useful for the study of other adaptogen drugs.

中文翻译：

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Rhodiola rosea L. 调节 CRH 激活的 BV2 细胞模型中的炎症过程。

背景技术 Rhodiola rosea L. (Crassulaceae) 多年来一直在几个国家的传统医学中用作适应原药物，能够保持体内平衡以响应压力刺激。目前，R. rosea 根和根茎被欧洲药品管理局归类为用于暂时缓解压力症状（例如疲劳和虚弱感）的传统草药产品。假设/目的 越来越多的证据表明神经炎症与应激反应有关。然而，几乎没有研究过神经炎症参数的调节是否可能参与 R. rosea 的抗应激作用。因此，这项工作的目的是研究 R 引发的分子炎症过程的可能调节。在促肾上腺皮质激素释放激素 (CRH) 刺激的 BV2 小胶质细胞体外模型中的玫瑰根和根茎乙醇提取物。方法 BV2 细胞用 CRH 100 nM 刺激，并评估细胞活力、细胞因子产生和热休克蛋白 70 (HSP70) 水平的变化。还分析了与炎症相关的细胞内途径，例如活化 B 细胞 (NF-κB) 核易位的核因子 kappa-轻链增强子和丝裂原活化蛋白激酶 (MAPK) 激活。结果 我们发现，R. rosea 提取物（2.7% m/m rosavin 和 1% m/m 红景天苷）20 µg/ml 能够通过抑制 NF-κB 核转位来抵消 CRH 的神经炎症作用，其作用机制涉及丝裂原活化蛋白激酶活化蛋白激酶 2 (MKK2) 的调节，细胞外信号调节激酶 1/2 (ERK 1/2) 和 c-Jun n-末端激酶 (JNK)，导致 HSP70 表达减少。结论这项工作扩展了对玫瑰红抗应激活性所涉及的细胞内机制的认识，并可能对其他适应原药物的研究有用。