Elephantopus scaber suppresses ConA-induced T cell activation by inhibiting NF-κB and Ca2+/NFAT signaling

Ethnopharmacological relevance Elephantopus scaber L. ( E. scaber ) is a heat-clearing and detoxifying traditional Chinese medicine. Clinically, it is used for treating some immuno-inflammatory diseases associated with excessive T cell activation. However, its action and mechanism on T cells are still ambiguous. Aim of the study This study aims to investigate the molecular mechanism of the ethanol extract of E.scaber (ESE) in ConA-induced T cell activation models. Materials and methods IL-2 transcription and translation levels were determined by RT- q PCR and ELISA. CD4 + naïve T cells were sorted using the flow cytometer. Western blot assay was used for determining intracellular protein levels. Cytoplasmic and mitochondrial Ca 2+ concentrations were measured by fluorometric assays. Results ESE not only dampened the proliferation of splenic lymphocytes, but also decreased IL-2 production in ConA-activated T cells without affecting its mRNA stability. It could inhibit the activation of NFAT and NF-κB pathways, showed as impeding the nuclear translocation of NFAT and p65. Regarding the upstream signaling, ESE significantly decreased cytoplasmic Ca 2+ (Ca 2+ [c] ) level in a model-independent manner. Although it failed to affect plasma membrane Ca 2+ -ATPase, Na + /Ca 2+ exchanger, and mitochondrial Ca 2+ uptake, it affected sarco/endoplasmic Ca 2+ -ATPase (SERCA) pathway. It also hindered IκBα phosphorylation and subsequent degradation. In vivo , ESE reduced IL-2 levels in local and systemic T cell activation models. Conclusion Through inhibiting the activation of SERCA/Ca 2+ [c] /NFAT and NF-κB pathways, ESE markedly decreased ConA-induced IL-2 production in vitro and in vivo . This study provides not only a modern explanation for the traditional uses of E. scaber , but also a scientific guidance for clinical practice.