Oxidative stress and inflammatory responses are nearly involved in the pathogenesis of various diseases, including acute lung injury (ALI). Orientin (Ori), a flavonoid component extracted from natural plants, displayed anti-inflammatory and antioxidant properties in our previous studies. In the current study, we aimed to investigate the amelioration effect of Ori on lipopolysaccharide (LPS)-induced ALI, and we further explored the potential molecular mechanisms. The present results indicated that Ori effectively alleviated LPS-induced ALI by improving the histological changes of lung; decreasing the lung W/D ratio and protein levels, the release of inflammatory cells and cytokines into the bronchoalveolar lavage fluid (BALF); inhibiting nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and high mobility group box 1 (HMGB1) protein expression; reducing malondialdehyde (MDA) formation and reactive oxygen species (ROS) generation; and increasing the content of glutathione (GSH) and superoxide dismutase (SOD) contents. Moreover, Ori treatment not only significantly suppressed the LPS-induced nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, and nuclear factor-kappa B (NF-κB) signaling pathway activation, but also obviously restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD (P) H: quinone oxidoreductase (NQO1), glutamate-cysteine ligase catalytic (GCLC), and heme oxygenase 1 (HO-1) expression in the lung; all of which are reduced by LPS. Taken together, these data suggested that Ori plays an important role in the protection against ALI by suppressing inflammation and oxidative stress which may be strongly related to the suppression of NLRP3 inflammasome and NF-κB activation, as well as the upregulation of the Nrf2 signaling pathway.
Keywords: Acute lung injury; Inflammation; Orientin; Oxidative stress; Signaling pathway.
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