Melia azedarach L. reduces pulmonary inflammation and mucus hypersecretion on a murine model of ovalbumin exposed asthma

J Ethnopharmacol. 2024 Feb 10:320:117426. doi: 10.1016/j.jep.2023.117426. Epub 2023 Nov 17.

Abstract

Ethnopharmacological relevance: Melia azedarach L. is a traditional medicinal plant used to control pain, pyrexia, inflammation and bacterial infections that possesses several pharmacological activities, including anti-inflammatory and antioxidant activities. Particularly, the root of M. azedarach was used as expectorant and anti-cough and asthma treatment. Based its properties, M. azedarach is expected to have a potential to treat allergic asthma, chronic inflammatory respiratory disease. However, there is no study on anti-asthmatic effects of M. azedarach and its mechanism of action until now.

Aim of the study: We investigated the active ingredient of M. azedarach fruit extract (MAE) using high-performance liquid chromatography (HPLC) and explored the therapeutic effects of MAE on pulmonary inflammation and mucus hypersecretion using a murine model of ovalbumin (OVA) exposed asthma.

Materials and methods: The ingredients of MAE were analyzed using HPLC. To develop allergic asthma model, the animals were sensitized (days 1 and 14) and the airway was challenged (from day 21-23) using OVA. MAE was administered by oral gavage once a day from day 18-23 at doses of 30 and 100 mg/kg.

Results: HPLC analysis revealed the presence of toosendanin in MAE. In asthmatic mice, MAE administration effectively suppressed the inflammatory cell counts in bronchoalveolar lavage fluid (BALF) along with a reduction in airway hyperresponsiveness. Moreover, MAE administration inhibited the production of proinflammatory cytokines and immunoglobulin E in BALF and serum of asthmatic mice, respectively. These results were similar to the results of histological examination showing a reduction in pulmonary inflammation and mucus hypersecretion. MAE elevated the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and superoxide dismutase 2, which in turn resulted in the suppression of matrix metallopeptidase-9 expression in lung tissue of asthmatic mice.

Conclusions: Altogether, MAE successfully inhibited allergic asthma in OVA-exposed mice. Thus, MAE could be a potential therapeutic remedy for treating allergic asthma.

Keywords: Airway inflammation; Asthma; MMP-9; Melia azedarach; Nrf2.

MeSH terms

  • Animals
  • Asthma* / pathology
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Disease Models, Animal
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Melia azedarach* / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mucus / metabolism
  • Ovalbumin
  • Pneumonia* / chemically induced
  • Pneumonia* / drug therapy
  • Pneumonia* / metabolism

Substances

  • Ovalbumin
  • Cytokines