Apigetrin is a flavonoid isolated from various herbal medicines such as Scutellaria baicalensis Georgi, Matricaria chamomilla, Stachys tibetica Vatke, and Teucrium gnaphalodes. In the present study, we investigated the inhibitory effects of apigetrin on neuroinflammation using the BV-2 microglia cell line. Our data revealed that apigetrin significantly reduced secretion and mRNA expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), in lipopolysaccharide (LPS)-stimulated BV-2 mouse microglia. Apigetrin also significantly decreased LPS-mediated production of prostaglandin E-2 (PGE(2)) level and nitric oxide (NO) production as well as expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) in BV-2 cells. In addition, apigetrin suppressed nuclear expression of nuclear factor kappa B (NF-kappa B) in LPS-stimulated BV-2 cells. Furthermore, apigetrin significantly impaired reactive oxygen species (ROS) generation and enhanced expression of antioxidant enzymes, hempxygenase 1 (HO-1) and nuclear factor-like 2 (Nrf2), in BV-2 cells. Apigetrin also increased 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, indicating antioxidative activity of apigetrin. Moreover, we found that apigetrin inhibited hydrogen peroxide (H2O2)-induced cell death in HT22 hippocampal cells. Overall, our findings indicate that apigetrin has inhibitory effects on neuroinflammation as well as antioxidation and neuroprotection, suggesting the potential prophylactic activity for neurodegenerative diseases through the inter-regulation of neuroinflammation, oxidative stress, and neuronal injury.
