Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway

J Ethnopharmacol. 2022 Jan 30:283:114701. doi: 10.1016/j.jep.2021.114701. Epub 2021 Oct 1.

Abstract

Ethnopharmacological relevance: Xuanfei Baidu Decoction (XFBD), one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, plays an important role in the treatment of mild and/or common patients with dampness-toxin obstructing lung syndrome.

Aim of the study: The present work aims to elucidate the protective effects and the possible mechanism of XFBD against the acute inflammation and pulmonary fibrosis.

Methods: We use TGF-β1 induced fibroblast activation model and LPS/IL-4 induced macrophage inflammation model as in vitro cell models. The mice model of lung fibrosis was induced by BLM via endotracheal drip, and then XFBD (4.6 g/kg, 9.2 g/kg) were administered orally respectively. The efficacy and molecular mechanisms in the presence or absence of XFBD were investigated.

Results: The results proved that XFBD can effectively inhibit fibroblast collagen deposition, down-regulate the level of α-SMA and inhibit the migration of fibroblasts. IL-4 induced macrophage polarization was also inhibited and the secretions of the inflammatory factors including IL6, iNOS were down-regulated. In vivo experiments, the results proved that XFBD improved the weight loss and survival rate of the mice. The XFBD high-dose administration group had a significant effect in inhibiting collagen deposition and the expression of α-SMA in the lungs of mice. XFBD can reduce bleomycin-induced pulmonary fibrosis by inhibiting IL-6/STAT3 activation and related macrophage infiltration.

Conclusions: Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway.

Keywords: COVID-19; IL-6/STAT3; Macrophage polarization; Pulmonary fibrosis; Xuanfei baidu decoction.

MeSH terms

  • Animals
  • COVID-19 Drug Treatment*
  • Cell Survival / drug effects
  • Drugs, Chinese Herbal* / pharmacology
  • Drugs, Chinese Herbal* / therapeutic use
  • Fibroblasts / drug effects
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks
  • Humans
  • Inflammation / drug therapy*
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Macrophages / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NIH 3T3 Cells
  • Phytotherapy
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / prevention & control
  • RAW 264.7 Cells
  • SARS-CoV-2*
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*

Substances

  • Drugs, Chinese Herbal
  • Interleukin-6
  • STAT3 Transcription Factor
  • Stat3 protein, mouse