Oroxylum indicum (L.) kurz seed extract prevents LPS-mediated BV2 microglial activation through NF-κB nuclear translocation and activation of the Akt/ERK1/2 signaling pathways

Background: Oroxylum indicum (L.) Kurz is an edible plant that is widely consumed in several Asian countries. In our previous study, it was demonstrated that Oroxylum indicum (L.) Kurz seed (OIS) extract attenuated oxidative stress and proinflammatory cytokines in activated microglia. However, the molecular mechanism remains unknown. Objectives: To confirm the antiinflammatory and antioxidative effects of OIS extract on and molecular mechanisms of OIS in lipopolysaccharide (LPS)-induced microglial activation. Materials and Methods: Nitrite and Chloro methyl derivative of 2', 7'-dichlorodihydrofluoresceindiacetate (CM-H₂DCFDA) assays were performed to examine the effect of OIS extract on LPS-induced nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Immunofluorescence and ELISA were performed to detect the levels of nuclear factor-κB (NF-κB) in the nucleus. Western blot analysis was performed to detect the phosphorylated (p-) form of Akt and extracellular-signal-regulated kinase 1/2 (ERK1/2). Results: OIS extract exhibited a significant and dose-dependent suppressive effect on LPS-induced NO and ROS production. Mechanistically, OIS extract attenuated the p-Akt and p-ERK1/2 signaling pathways, thereby inhibiting the LPS-induced NF-κB nuclear translocation. Conclusion: OIS extract exerts anti-oxidative effects by suppressing ROS production, and anti-inflammatory effects by inhibiting NO in activated BV2 microglial cells. Mechanistically, OIS extract could inhibit the Akt/ERK1/2-mediated NF-κB pathway. OIS extract may act as a promising functional food for the alleviation of neuroinflammation in neurodegenerative diseases.