Anatabine attenuates ovalbumin-induced asthma via oxidative stress and inflammation mitigation and Nrf2/HO-1 signaling upregulation in rats

Life Sci. 2022 Nov 1:308:120954. doi: 10.1016/j.lfs.2022.120954. Epub 2022 Sep 11.

Abstract

Aims: Asthma affects a large number of people worldwide and is characterized by chronic allergic airway inflammation. Anatabine is a natural alkaloid that is structurally similar to nicotine and found in the Solanaceae family of plants, with anti-inflammatory properties. Consequently, this study aimed to evaluate the potential therapeutic effect of anatabine against asthma.

Main methods: Ovalbumin was used to induce asthma in rats. Two asthmatic groups were treated with low and high doses of anatabine.

Key findings: Asthmatic animals experienced increased total leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF), bronchitis, and bronchopneumonia associated with mast cell infiltration. Additionally, inducible nitric oxide synthase immunostaining was observed, with decreased pulmonary antioxidant capacity and enzymes and decreased Nrf2 and HO-1 gene expression while increased NFκB-P65 expression. Interestingly, asthmatic animals treated with anatabine at both doses showed dose-dependently decreased inflammatory cells and cytokine levels within BALF reduced inflammation in the airways through decreased mast cell infiltration within lung tissues and increased antioxidant enzymes and Nrf2 and Ho-1 expression levels.

Significance: Our results highlight the potential beneficial effect of anatabine against asthma through anti-inflammatory and antioxidant mechanisms. Therefore, anatabine is a promising candidate for pulmonary asthma treatment.

Keywords: Anatabine; Asthma; Inflammation; Ovalbumin; Oxidative stress; Surfactant.

MeSH terms

  • Alkaloids* / metabolism
  • Alkaloids* / pharmacology
  • Alkaloids* / therapeutic use
  • Animals
  • Anti-Inflammatory Agents
  • Antioxidants / metabolism
  • Asthma* / chemically induced
  • Asthma* / drug therapy
  • Asthma* / metabolism
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Lung / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Nicotine / pharmacology
  • Nitric Oxide Synthase Type II / metabolism
  • Ovalbumin
  • Oxidative Stress
  • Pyridines
  • Rats
  • Up-Regulation

Substances

  • Alkaloids
  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • NF-E2-Related Factor 2
  • Pyridines
  • anatabine
  • Nicotine
  • Ovalbumin
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat