Isoalantolactone protects LPS-induced acute lung injury through Nrf2 activation

Microbial Pathogenesis
Cheng-Bo YuanHai-Yan Zhou

Abstract

Isoalantolactone (ISO), a sesquiterpene lactone isolated from Inula helenium, is known to have anti-inflammatory activity. Here, using a mouse model of acute lung injury, we investigated the effects of ISO on lung inflammation in vivo. ISO (2.5, 5, 10 mg/kg) was administered 1 h before LPS treatment. Histopathological changes suggested that ISO attenuated the injury of lung tissues induced by LPS. ISO also inhibited LPS-induced MPO activity, MDA content, lung W/D ratio, and the production of inflammatory cytokines TNF-α and IL-1β. LPS decreased the activities of the antioxidant enzymes SOD, GPX, and CAT and the decreases were inhibited by ISO. Further studies were performed to detect the Nrf2 and NF-κB signaling pathway. The results showed that ISO significantly suppressed LPS-induced NF-κB activation, as well as PI3K and AKT phosphorylation. Additionally, the expression of Nrf2 and HO-1 were dose-dependently up-regulated by the treatment of ISO. Taken together, the results indicate the protective action of ISO against LPS-induced ALI were through activation of the Nrf2 signaling pathway.

Citations

May 11, 2020·International Immunopharmacology·Jinwei LuRongxin He
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jimena BorgoValeria P Sülsen
Jul 4, 2021·International Journal of Biological Macromolecules·Jing MengHonglun Wang

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