Anti-inflammatory and Protective Effect of Linggui Zhugantang on LPS-induced Acute Lung Injury in Mice via NF-κB Signaling Pathway
10.13422/j.cnki.syfjx.20230902
- VernacularTitle:基于NF-κB信号通路探讨苓桂术甘汤对脂多糖诱导的小鼠急性肺损伤的抗炎保护作用
- Author:
Wei DING
1
;
Wenlai WANG
2
;
Zhanzhan HE
2
;
Xiangyun CHEN
1
;
Zhenhong LIU
3
;
Xuguang TAO
2
;
Peizhang ZHAO
4
;
Zhen YANG
1
;
Hongxia ZHAO
2
Author Information
1. School of Traditional Chinese Medicine(TCM),Beijing University of Chinese Medicine, Beijing 102488,China
2. Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China
3. Encephalopathy Research Institute,Beijing University of Chinese Medicine,Beijing 100700,China
4. West China Clinical Medical College,Sichuan University,Chengdu 610041,China
- Publication Type:Journal Article
- Keywords:
Linggui Zhugantang;
lipopolysaccharide;
acute lung injury;
inflammation;
nuclear factor-κB (NF-κB) signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(15):14-21
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the therapeutic effect and underlying mechanism of Linggui Zhugantang on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. MethodSeventy-two 7-week-old C57BL/6 mice of SPF grade were randomly divided into a normal group, a model group, a dexamethasone group (5 mg·kg-1), and high-, medium-, and low-dose Linggui Zhugantang groups (9.36, 4.68,2.34 g·kg-1), with 12 mice in each group. Except for the normal group, the remaining groups underwent intranasal instillation of LPS (50 μg per mouse) for the induction of the ALI model. The treatment groups received oral administration for 7 days prior to modeling. After 12 hours of modeling, mouse lung tissues were taken to measure the wet/dry weight ratio (W/D). Hematoxylin-eosin (HE) staining was performed to observe the pathological morphological changes in lung tissues. Bronchoalveolar lavage fluid (BALF) was collected for total cell count using a cell counter, and Wright-Giemsa staining was conducted to classify and quantify inflammatory cells (neutrophils and macrophages). Enzyme-linked immunosorbent assay (ELISA) was used to determine the expression levels of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF. Western blot analysis was performed to detect the expression of nuclear factor-κB (NF-κB) inhibitory protein α (IκBα), NF-κB p65, and their phosphorylated proteins, and the ratio of phosphorylated protein/total protein was calculated. ResultCompared with the normal group, the model group exhibited severe lung tissue damage, disrupted alveolar structure, thickened alveolar walls, infiltration of extensive inflammatory cells and red blood cells, and significantly aggravated lung edema (P<0.01). The total cell count, inflammatory cell count, expression levels of IL-6, and TNF-α in BALF, as well as NF-κB p65 and phosphorylated IκBα in lung tissues, were significantly upregulated in the model group (P<0.01). Compared with the model group, high-, medium-, and low-dose Linggui Zhugantang groups, as well as the dexamethasone group, showed improved lung injury, reduced lung edema (P<0.01), downregulated total cell count, neutrophil count, expression levels of IL-6 and TNF-α in BALF, and NF-κB p65 and phosphorylated IκBα in lung tissues (P<0.01), and reduced macrophage count (P<0.05). ConclusionLinggui Zhugantang has anti-inflammatory and protective effects on LPS-induced ALI in mice, effectively reducing inflammation and promoting diuresis and edema elimination. Its mechanism may be related to the inhibition of NF-κB pathway activation.