Forsythiae Fructuse extracts alleviates LPS-induced acute lung injury in mice by regulating PPAR-γ/RXR-α in lungs and colons

免疫印迹 医学 TLR4型 药理学 过氧化物酶体增殖物激活受体 地塞米松 炎症 受体 脂多糖 病理 内科学 化学 基因 生物化学
作者
Jing Wang,Lin Luo,Xingtao Zhao,Xinyan Xue,Li Liao,Ying Deng,Mengting Zhou,Cheng Peng,Yunxia Li
出处
期刊:Journal of Ethnopharmacology [Elsevier]
卷期号:293: 115322-115322 被引量:15
标识
DOI:10.1016/j.jep.2022.115322
摘要

Forsythiae Fructuse (FF), the dried fruit of Forsythia suspensa (Thunb.) Vahl, is used as a traditional Chinese medicine that has been reported to exert good anti-inflammatory effects in the treatment of many lung diseases.The purpose of this study was to investigate the anti-inflammatory mechanism of FF in the treatment of acute lung injury (ALI) based on gut-lung axis.ALI model was established by the intratracheal instillation of 5 mg/kg LPS in ICR mice. Mice were administered intragastrically with dexamethasone (DEX), and low-dose, medium-dose and high-dose of FF extracts (LFF, MFF and HFF) in addition to the mice of control (CON) and model (MOD) groups. Pathological observation and inflammation scoring of lung tissues were based on HE staining. Limulus lysate assay was used to detect endotoxin levels in serum. Western blot and Real-time quantitative PCR were respectively applied to detect the protein and mRNA expressions in both lung and colon tissues.Lung pathological injury, inflammatory score and inflammatory genes (IL-6, IL-1β, TNF-α) could be effectively suppressed by FF in LPS-induced ALI mice. FF also increased the proteins of epithelial markers (E-cadherin, ZO-1 and Claudin-1) in lung and colon tissues, and decreased colonic inflammatory genes for protecting the epithelial barriers of lung and colon. The protein expression of TLR4/MAPK/NF-κB inflammatory signaling pathway in lung and colon was significantly inhibited by FF via the regulation of PPAR-γ, a nuclear hormone receptor that forms the heterodimer with RXR-α to inhibit inflammatory gene transcription. More specifically, FF promoted the upregulation of protein, phosphorylated proteins and genes of PPAR-γ/RXR-α in lungs, while inhibited the protein overexpression and phosphorylation of PPAR-γ/RXR-α in colons.FF exhibited anti-inflammatory effects and protected the epithelial barriers in lungs and colons by regulating PPAR-γ/RXR-α in the treatment of LPS-induced ALI.
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