Pyrus ussuriensis Maxim 70% ethanol eluted fraction ameliorates inflammation and oxidative stress in LPS-induced inflammation in vitro and in vivo

Pyrus ussuriensis Maxim (PUM) is a popular fruit among consumers, and also used as medical diet for dissolving phlegm and arresting cough. The present study aims to investigate the potential protective effect of P. ussuriensis Maxim 70% ethanol eluted fraction (PUM70) on lipopolysaccharide (LPS)-induced alveolar macrophages and acute lung injury (ALI) in mice. A total of 18 polyphenol compounds were tentatively identified in PUM70 by mass spectrometry (MS) analysis. The results in vivo suggested that PUM70 treatment could effectively alleviate the histological changes, and significantly inhibit the activity of myeloperoxidase (MPO) and the expression of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6)). The cell test results show that PUM70 exerted its protective effect by suppressing the messenger RNA (mRNA) expression levels (inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and decreasing nitric oxide (NO) and prostaglandin 2 (PGE2) contents. In addition, it also inhibited the overproduction of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6). Furthermore, PUM70 induced the production of heme oxygenase 1 (HO-1) protein and nuclear translocation of Nrf2 (nuclear factor erythroid 2-related factor 2), indicating that PUM70 could mitigate oxidative injury via the Nrf2/HO-1 pathway. Moreover, PUM70 inhibited LPS-induced inflammation by blocking the phosphorylation of mitogen-activated protein kinases (MAPKs). The above results indicate that PUM70 has protective effects on LPS-induced ALI, possibly be related to the inhibition of MAPK and Nrf2/HO-1 signaling pathways.