2 '-O-galloylhyperin attenuates LPS-induced acute lung injury via upregulation antioxidation and inhibition of inflammatory responses in vivo

摘要

2'-O-galloylhyperin, an active flavonol glycoside compound with remarkable anti-immune activity, was isolated from Pyrola [P. incarnate Fisch.]. However, the evidence of anti-inflammatory activity in pulmonary diseases was still not convincing. The aim of the present study was (1) to investigate the effect of 2'-O-galloylhyperin on LPS-induced acute lung injury in mice, and (2) to identify the mechanisms of attenuation of inflammatory responses. The results demonstrated that 2'-O-galloylhyperin significantly reduced LPS-induced inflammation damage in a dose-dependent manner. After LPS challenge, treatment with 2'-O-galloylhyperin reduced the production of pro-inflammatory cytokines and chemokines, and also improved LPS-induced lung histopathology changes. 2'-O-galloylhyperin also increased the activities of antioxidant enzymes, including SOD and GSH-Px to maintain cellular redox homeostasis. Furthermore, 2'-O-galloylhyperin inhibited translocation of nuclear factor (NF-KB) activation and suppressed phosphorylation of MAPK signaling pathway consisting of p38, ERK, JNK. In addition, 2'-O-galloylhyperin enhanced heme oxygenase-1 (HO-1) expression to block LPS-induced inflammation via activating nuclear factor-crythroid 2-related factor (Nrf2). Moreover, 2'-O-galloylhyperin induced adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation. 2'-O-galloylhyperin attenuated LPS-induced acute lung injury by inhibiting the MAPK and NF-kappa B signaling pathways, presumably related to up-regulation of the AMPK and Nrf2 signaling pathways. Furthermore, 2'-O-galloylhyperin is a potential protective antioxidant to protect lung tissues from the acute injury.