Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway

Pharm Biol. 2022 Dec;60(1):1520-1532. doi: 10.1080/13880209.2022.2104327.

Abstract

Context: Asthma is a common respiratory system disease. Louki Zupa decoction (LKZP), a traditional Chinese medicine, presents a promising efficacy against lung diseases.

Objective: To investigate the pathogenic mechanism of asthma and reveal the intervention mechanism of LKZP.

Materials and methods: Forty-eight female Balb/c mice were randomly divided into 6 groups: normal control group (NC), ovalbumin (OVA)/saline asthma model group, OVA/LL group, OVA/LM group, OVA/LH group and OVA/DEX group (n = 8 per group). The asthmatic mice were modelled through intraperitoneal injecting and neutralizing OVA. LKZP decoction was administrated by gavage at the challenge stage for seven consecutive days (2.1, 4.2 and 8.4 g/kg/day). We investigated the change in lung function, airway inflammation, mucus secretion and TH-1/TH-2-related cytokines. We further verify the activated status of the IL-33/ST2/NF-κB/GSK3β/mTOR signalling pathway.

Results: LKZP was proved to improve asthmatic symptoms, as evidenced by the down-regulated airway resistance by 36%, 58% and 53% (p < 0.01, p < 0.001 vs. OVA/saline group), up-regulated lung compliance by 102%, 114% and 111%, decreased airway inflammation and mucus secretion by 33%, 40% and 33% (p < 0.001 vs. OVA/saline group). Moreover, the content of cytokines in BALF related to airway allergy (such as IgE) and T helper 1/T helper 2 cells (like IL-2, IL-4, IL-5, IL-13, TNF-α and IFN-γ), were also markedly reduced by 13-65% on LKZP intervention groups compared with model group. Mechanistic research revealed that the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway was activated in the OVA/saline group and LKZP significantly down-regulated this pathway.

Discussion and conclusion: LKZP improves lung function, airway inflammation, mucus secretion and correct immune imbalance by intervening with the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway, presenting a promising therapeutic choice for asthma.

Keywords: Allergic asthma; interleukin-33; mucus secretion; suppression of tumorigenicity 2.

Publication types

  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Animals
  • Asthma*
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Inflammation / pathology
  • Interleukin-1 Receptor-Like 1 Protein / metabolism
  • Interleukin-33 / metabolism
  • Lung / metabolism
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B* / metabolism
  • Ovalbumin
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Cytokines
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • NF-kappa B
  • Ovalbumin
  • Glycogen Synthase Kinase 3 beta
  • TOR Serine-Threonine Kinases

Grants and funding

This work was financially supported by grants from the National Key R&D Program of China [2018YFC1708300] and the National Natural Science Foundation of China [82004318].