Research Paper Volume 11, Issue 18 pp 7805—7816

A novel chalcone derivative exerts anti-inflammatory and anti-oxidant effects after acute lung injury

Yuting Lin 1, , Man Zhang 2, , Qingdi Lu 1, , Jingwen Xie 3, , Jianzhang Wu 3, , Chengshui Chen 1, ,

  • 1 Department of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325006, China
  • 2 Department of Orthopedics, The Second Affiliated Hospital Zhejiang University School of Medicine, Zhejiang 325000, China
  • 3 Department of Pharmacy, Pharmacy School, Wenzhou Medical University, Wenzhou, Zhejiang 325006, China

received: August 1, 2019 ; accepted: September 9, 2019 ; published: September 24, 2019 ;

https://doi.org/10.18632/aging.102288
How to Cite

Copyright © 2019 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We explored the effects of compound 33, a synthetic chalcone derivative with antioxidant activity, on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Compound 33, dexamethasone or vehicle was administered intragastrically to mice 6 h before intratracheal instillation of LPS. After 24 h, the effects of compound 33 on alveolar structural damage were evaluated by assessing lung morphology and the wet/dry weight ratio. Protein and proinflammatory cytokine levels and superoxide dismutase activity were also examined in the cell free supernatant of bronchoalveolar lavage fluid. Additionally, we investigated the anti-inflammatory and antioxidant activity of compound 33 in vitro and its effects on the MAPK/NF-κB and Nrf2/HO-1 pathways. Pretreatment with compound 33 prevented LPS-induced structural damage, tissue edema, protein exudation, and overproduction of proinflammatory mediators. The effects of compound 33 were similar to or greater in magnitude than those of the positive control, dexamethasone. Moreover, compound 33 exerted anti-inflammatory and antioxidant effects in vitro by inhibiting the MAPK/NF-κB pathway and activating the Nrf2/HO-1 pathway. Compound 33 may therefore be a promising candidate treatment for ALI.

Abbreviations

ALI: Acute lung injury; LPS: Lipopolysaccharide; ROS: Reactive oxygen species; H2O2: Hydrogen peroxide; MAPK: Mitogen-activated protein kinase; NF-κB: Nuclear factor κB; TNF-α: Tumor necrosis factor-α; IL-6: Interleukin-6; COX2: Cyclooxygenase; iNOS: Inducible nitric oxide synthase; HO-1: Heme oxygenase-1; Nrf2: Nuclear factor erythroid-2-related factor 2; BALF: bronchoalveolar lavage fluid; WW: Wet weights; DW: Dry weights; p- IκBα: phosphorylated-IκBα; ERK: Extracellular signal-regulated kinase; JNK: Jun N-terminal kinase; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; SnPP: Tin protoporphyrin IX; PBS: Phosphate buffered saline; DMEM: Dulbecco’s modified Eagle’s medium; qRT-PCR: Quantitative reverse transcriptase-polymerase chain reaction.