Open AccessChrysosplenol D protects mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via TLR4-MAPKs/NF-κB signaling pathways
Author(s) -
Qinqin Zhang,
Aozi Feng,
Mengnan Zeng,
Beibei Zhang,
Jingya Shi,
Ya-Xin Lv,
Bing Cao,
Chenxin Zhao,
Mengya Wang,
Yifan Ding,
Xiaoke Zheng
Publication year - 2021
Publication title -
innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.921
H-Index - 69
eISSN - 1753-4267
pISSN - 1753-4259
DOI - 10.1177/17534259211051069
Subject(s) - oxidative stress , apoptosis , tlr4 , inflammation , p38 mitogen activated protein kinases , bronchoalveolar lavage , reactive oxygen species , chemistry , western blot , mapk/erk pathway , proinflammatory cytokine , signal transduction , immunology , microbiology and biotechnology , biology , lung , medicine , biochemistry , gene
This study investigated the effect and mechanism of chrysosplenol D (CD) on LPS-induced acute lung injury in mice. Histological changes in the lungs were measured by hematoxylin-eosin staining. The levels of IL-6, IL-1β, and TNF-α in the bronchoalveolar lavage fluid were detected by ELISA. The levels of oxidative stress were detected by the cuvette assay. Immune cells in peripheral blood, the levels of reactive oxygen species, and apoptosis of primary lung cells were detected by flow cytometry. The mRNA levels of TLR4, MyD88, IL-1β, and NLRP3 were measured by quantitative real-time polymerase chain reaction. The levels of proteins in apoptosis and the TLR4-MAPKs/NF-κB signaling pathways were detected by Western blot. Hematoxylin-eosin staining showed that CD could improve lung injury; decrease the levels of inflammatory factors, oxidative stress, reactive oxygen species, and cell apoptosis; and regulate the immune system. Moreover, CD could down-regulate the mRNA levels of TLR4, MyD88, NLRP3, and IL-1β in lung, and the protein levels of Keap-1, Cleaved-Caspase-3/Caspase-3, Cleaved-Caspase-9/Caspase-9, TLR4, MyD88, p-ERK/ERK, p-JNK/JNK, p-p38/p38, p-p65/p65, NLRP3, and IL-1β, and up-regulated the levels of Bcl-2/Bax, p-Nrf2/Nrf2, and HO-1. The results suggested that CD could protect mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via the TLR4-MAPKs/NF-κB signaling pathways.