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

Abstract

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 Acanthopanax koreanum 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.

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“…2020). This plant is mainly distributed in China, North Korea, Japan, and Russia ( Kawano et al, 2021 ), and related studies have confirmed that it has multiple pharmacological benefits, such as anti-neuroinflammation, antibacterial, anti-cancer ( Kim et al, 2018 ; Kawano et al, 2021 ), anti-inflammatory ( Lee et al, 2021 ), anti-oxidation ( Kim et al, 2015 ), anti-AChE, and anti-BuChE features ( Li et al, 2021 ). Additionally, it has positive effects on the cardiovascular ( Jin et al, 2020 ), central nervous, and immune systems ( Jia et al, 2021 ).…”