Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF- κ B signaling cascade and inhibiting NLRP3 inflammasome activation

Front Immunol. 2023 Oct 25:14:1285550. doi: 10.3389/fimmu.2023.1285550. eCollection 2023.

Abstract

Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated with the pathogenesis of ALI. Since ALI poses a huge challenge to human health, it is urgent to tackle this affliction with therapeutic intervention. Qinhuo Shanggan oral solution (QHSG), a traditional Chinese herbal formula, is clinically used for effective medication of various lung diseases including ALI, with the action mechanism obscure. In the present study, with the rat model of lipopolysaccharide (LPS)-induced ALI, QHSG was unveiled to ameliorate ALI by alleviating the pathological features, reversing the alteration in white blood cell profile and impeding the production of inflammatory cytokines through down-regulation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. In LPS-stimulated RAW264.7 mouse macrophages, QHSG was discovered to hinder the generation of inflammatory cytokines by lessening TLR4/NF-κB signaling pathway activity and weakening NLRP3 inflammasome activation. Taken together, QHSG may resolve acute lung injury, attributed to its anti-inflammation and immunoregulation by attenuation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. Our findings provide a novel insight into the action mechanism of QHSG and lay a mechanistic foundation for therapeutic intervention in acute lung injury with QHSG in clinical practice.

Keywords: NF- kappa B; NLRP3; TLR4 (toll-like receptor 4); acute lung injury (ALI); cytokine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury* / metabolism
  • Animals
  • Cytokines / metabolism
  • Humans
  • Inflammasomes / metabolism
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred NOD
  • NF-kappa B* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Pandemics
  • Rats
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism

Substances

  • NF-kappa B
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Toll-Like Receptor 4
  • Lipopolysaccharides
  • Cytokines
  • TLR4 protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the National Natural Science Foundation of China (No. 81573813), the Science & Technology Department of Sichuan Province of China (No. 2023NSFSC0653), the Sichuan Provincial Administration of Traditional Chinese Medicine of China (Nos. 2021XYCZ007 and 2021MS447), the Health Commission of Sichuan Province of China (No. 21PJ107), and the Excellent Talent Program of Chengdu University of Traditional Chinese Medicine of China (No. GJJJ2021003).