Impressic Acid Attenuates the Lipopolysaccharide-Induced Inflammatory Response by Activating the AMPK/GSK3β/Nrf2 Axis in RAW264.7 Macrophages

• Main Authors: Gi Ho Lee, Ji Yeon Kim, Sun Woo Jin, Thi Hoa Pham, Jin Song Park, Chae Yeon Kim, Jae Ho Choi, Eun Hee Han, Young Ho Kim, Hye Gwang Jeong
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: International Journal of Molecular Sciences
• Subjects: impressic acid; anti-inflammation; Nrf2; AMPK; GSK3β
• Online Access: https://www.mdpi.com/1422-0067/22/2/762
• ISSN: 1661-6596; 1422-0067

Inflammatory diseases are caused by excessive inflammation from pro-inflammatory mediators and cytokines produced by macrophages. The Nrf2 signaling pathway protects against inflammatory diseases by inhibiting excessive inflammation via the regulation of antioxidant enzymes, including HO-1 and NQO1. We investigated the anti-inflammatory effect of impressic acid (IPA) isolated from <i>Acanthopanax koreanum</i> on the lipopolysaccharide (LPS)-induced inflammation and the underlying molecular mechanisms in RAW264.7 cells. IPA attenuated the LPS-induced production of pro-inflammatory cytokines and reactive oxygen species, and the activation of the NF-κB signaling pathway. IPA also increased the protein levels of Nrf2, HO-1, and NQO1 by phosphorylating CaMKKβ, AMPK, and GSK3β. Furthermore, ML385, an Nrf2 inhibitor, reversed the inhibitory effect of IPA on LPS-induced production of pro-inflammatory cytokines in RAW264.7 cells. Therefore, IPA exerts an anti-inflammatory effect via the AMPK/GSK3β/Nrf2 signaling pathway in macrophages. Taken together, the findings suggest that IPA has preventive potential for inflammation-related diseases.