Xuanfei Baidu formula alleviates impaired mitochondrial dynamics and activated NLRP3 inflammasome by repressing NF-κB and MAPK pathways in LPS-induced ALI and inflammation models

Phytomedicine. 2023 Jan:108:154545. doi: 10.1016/j.phymed.2022.154545. Epub 2022 Nov 9.

Abstract

Background: Xuanfei Baidu Formula (XBF) is an effective traditional Chinese medicine (TCM) remedy for treating coronavirus disease 2019 (COVID-19) in China. This herbal medicine has shown effects in reducing clinical symptoms and shortening the average length of hospital stay for COVID-19 patients. Previous studies have demonstrated that XBF alleviates acute lung injury (ALI) by regulating macrophage-mediated immune inflammation, but the mechanisms of action remain elusive.

Purpose: This study aimed to evaluate the lung-protective and anti-inflammatory effects of XBF and its underlying mechanisms.

Methods: Here, XBF's effects were investigated in an ALI mouse model induced by inhalation of atomized lipopolysaccharide (LPS). Besides, the LPS-induced inflammation model in RAW264.7 cells was used to clarify the underlying mechanisms of XBF against ALI.

Results: Our results showed that XBF treatment alleviated LPS-induced lung injury, as evidenced by reduced histopathological changes, pulmonary alveoli permeability, fibrosis, and apoptosis in the lung tissues. In addition, inflammation was alleviated as shown by decreased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β in serum and bronchoalveolar lavage fluid (BALF), and reduced white blood cell (WBC) count in BALF. Furthermore, consistent with the in vivo assay, XBF inhibited LPS-induced inflammatory cytokines release and pro-inflammatory polarization in RAW264.7 cells. Mechanistically, XBF increased mitochondrial fusion by upregulating Mfn1 and attenuated NLRP3 inflammasome activation by repressing Casp11, respectively, to inhibit NF-κB and MAPK pathways, thus repressing pro-inflammatory macrophage polarization.

Conclusion: In this study, we demonstrate that XBF exerts anti-ALI and -inflammatory effects by recovering mitochondrial dynamics and reducing inflammasome activation, providing a biological illustration of the clinical efficacy of XBF in treating COVID-19 patients.

Keywords: COVID-19; Inflammation; Mitochondrial dynamics; NLRP3 inflammasome; Xuanfei Baidu Formula.

MeSH terms

  • Acute Lung Injury* / chemically induced
  • Acute Lung Injury* / drug therapy
  • Animals
  • COVID-19 Drug Treatment*
  • Inflammasomes
  • Inflammation / drug therapy
  • Interleukin-6
  • Lipopolysaccharides
  • MAP Kinase Signaling System
  • Mice
  • Mitochondrial Dynamics
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Tumor Necrosis Factor-alpha

Substances

  • Inflammasomes
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Tumor Necrosis Factor-alpha
  • xuanfei baidu