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Rotundic acid reduces LPS ‐induced acute lung injury in vitro and in vivo through regulating TLR4 dimer
Author(s) -
Li XinXing,
Yuan Renyikun,
Wang QinQin,
Han Shan,
Liu Zhenjie,
Xu Qiongming,
Yang Shilin,
Gao Hongwei
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.7152
Subject(s) - pharmacology , in vivo , tlr4 , nitric oxide , tumor necrosis factor alpha , nitric oxide synthase , chemistry , inflammation , medicine , immunology , biology , microbiology and biotechnology , organic chemistry
Acute lung injury (ALI) is a serious clinical disease. Rotundic acid (RA), a natural ingredient isolated from Ilex rotunda Thunb, exhibits multiple pharmacological activities. However, RA's therapeutic effect and mechanism on ALI remain to be elucidated. The present study aimed to further clarify its regulating effects on inflammation in vitro and in vivo. Our results indicated that RA significantly inhibited the overproduction of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), cyclooxygenase‐2 (COX‐2), and inducible nitric oxide synthase (iNOS). RA decreased ROS production and calcium influx. In addition, RA inhibited the activation of PI3K, MAPK, and NF‐κB pathways and enhanced the activity of nuclear factor E2‐related factor 2 (Nrf2) signaling. The cellular thermal shift assay and docking results indicated that RA bind to TLR4 to block TLR4 dimerization. Furthermore, RA pretreatment effectively inhibited ear edema induced by xylene and LPS‐induced endotoxin death and had a protective effect on LPS‐induced ALI. Our findings collectively indicated that RA has anti‐inflammatory effects, which may serve as a potential therapeutic option for pulmonary inflammation.