Rhodiola rosea L. modulates inflammatory processes in a CRH-activated BV2 cell model

Abstract

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.

Keywords: CRH; HSP70; MAPK; NF-κB; Rhodiola rosea L.; microglia.