Nuclear factor E2-related factor 2 (Nrf2) is the master regulator of antioxidant enzymes and is known to act on the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Few studies have examined the bioactivity of halleridone. Herein, we investigated whether halleridone, which was isolated from the stems of the plant Cornus walteri, could regulate Nrf2-mediated heme oxygenase (HO)-1 expression and prevent intramicroglial inflammation induced by amyloid beta (Aβ)1-42 overexpression. Biochemical and molecular experiments, such as real-time polymerase chain reaction, Western blot analysis, immunocytochemistry, immunofluorescence, and luciferase reporter gene assays, were performed. The results demonstrated that halleridone promoted the upregulation of Nrf2 expression and its translocation to the nucleus, thereby activating antioxidant response element gene transcription and HO-1 expression in murine hippocampal HT22 cells. Additionally, halleridone removed intramicroglial Aβ1-42 and suppressed the production of inflammatory mediators such as interleukin (IL)-1β, IL-6, prostaglandin E2, and nitric oxide (NO) induced by artificially overexpressed Aβ1-42 and decreased pNF-κB accumulation in the nucleus and the expression of inducible NO synthase and cyclooxygenase II in BV-2 cells. In conclusion, halleridone activated Nrf2-mediated HO-1 expression and inhibited Aβ1-42-overexpressed microglial BV-2 cell activation. These observations suggest that halleridone may have therapeutic potential for targeting neurodegeneration through neuroinflammation.
Bibliographical noteFunding Information:
This work was supported, in part, by grants from the Marine Biotechnology Program of the Ministry of Oceans and Fisheries (PJT200669) and from the Bio and Technology Development (2016 M3A9A5919548) of the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, Information and Communication Technology (ICT) and Future Planning.
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Nutrition and Dietetics