β-Asarone (cis-2,4,5-trimethoxy-1-allyl phenyl), attenuates pro-inflammatory mediators by inhibiting NF-κB signaling and the JNK pathway in LPS activated BV-2 microglia cells

Abstract

Acorus species contains diverse pharmacologically active phytochemicals including α-asarone, β-asarone, and eugenol. We determined if β-asarone isolated from Acorus gramineus (AG) Solander would be efficacious in protecting BV-2 microglia cells from lipopolysaccharide (LPS)-induced stress signaling. BV-2 microglial cells were pretreated with an AG ethanol extract (1, 10, and 100 μg/mL) or β-asarone (10, 50, and 100 μM) prior to exposure to LPS (100 ng/mL). AG and β-asarone inhibited LPS-induced production of nitric oxide in a dose-dependent manner. The mRNA and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 also decreased dose dependently following AG and β-asarone treatments. Immunostaining and immunoblot studies revealed that β-asarone also suppressed nuclear factor (NF)-κB activation by blocking IkB degradation. Further mechanistic studies revealed that β-asarone acted through the JNK/MAPK pathway. Taken together, our findings demonstrate that β-asarone exhibits anti-inflammatory effects by suppressing the production of pro-inflammatory mediators through NF-κB signaling and the JNK pathways in activated microglial cells and might be developed as a promising candidate to treat various neuroinflammatory diseases.

Keywords: COX-2; Microglia; NF-κB; Neurodegenerative disease; iNOS; β-Asarone.