Stigmasterol alleviates allergic airway inflammation and airway hyperresponsiveness in asthma mice through inhibiting substance-P receptor

Pharm Biol. 2023 Dec;61(1):449-458. doi: 10.1080/13880209.2023.2173252.

Abstract

Context: Stigmasterol has significant anti-arthritis and anti-inflammatory effects, but its role in immune and inflammatory diseases is still unclear.

Objective: The potential advantages of stigmasterol in asthma were explored in IL-13-induced BEAS-2B cells and asthmatic mice.

Materials and methods: The optimal target of stigmasterol was confirmed in asthma. After detecting the cytotoxicity of stigmasterol in BEAS-2B cells, 10 μg/mL and 20 μg/mL stigmasterol were incubated with the BEAS-2B cell model for 48 h, and anti-inflammation and antioxidative stress were verified. Asthmatic mice were induced by OVA and received 100 mg/kg stigmasterol for 7 consecutive days. After 28 days, lung tissues and BAL fluid were collected for the following study. To further verify the role of NK1-R, 0.1 μM WIN62577 (NK1-R specific antagonist), and 1 μM recombinant human NK1-R protein were applied.

Results: NK1-R was the potential target of stigmasterol. When the concentration of stigmasterol is 20 μg/mL, the survival rate of BEAS-2B cells is about 98.4%, which is non-toxic. Stigmasterol exerted anti-inflammation and antioxidant stress in a dose-dependent manner and decreased NK1-R expression in IL-13-induced BEAS-2B. Meanwhile, in vivo assay also indicated the anti-inflammation and antioxidant stress of stigmasterol after OVA challenge. Stigmasterol inhibited inflammation infiltration and mucus hypersecretion, and NK1-R expression.

Discussion and conclusions: The protective effect of stigmaterol on asthma and its underlying mechanism have been discussed in depth, providing a theoretical basis and more possibilities for its treatment of asthma.

Keywords: Inflammation response; mucus hypersecretion; oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants
  • Asthma*
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Inflammation / drug therapy
  • Interleukin-13 / pharmacology
  • Lung
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Receptors, Neurokinin-1 / metabolism
  • Respiratory Hypersensitivity*
  • Stigmasterol* / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Interleukin-13
  • Ovalbumin
  • Receptors, Neurokinin-1
  • Stigmasterol

Grants and funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.