Effects of total alkaloids from Alstonia scholaris (L.) R. Br. on ovalbumin-induced asthma mice

Abstract

Ethnopharmacological relevance: More than 300 million people worldwide suffer from asthma, a chronic respiratory inflammatory disease. Total alkaloids (TA) were extracted from the ethnic medicinal plant Alstonia solaris (L.) R.Br., which is used to treat respiratory diseases. They may be effective drugs for treating asthma, but research is still needed to determine their effectiveness and mechanism in treating asthma.

Aim of the study: To further understand TA's role in the treatment of asthma and to support the phase II trial of the drug.

Materials and methods: In this study, we investigated the effects of TA in a mouse asthma model produced by Ovalbumin (OVA). H&E and PAS staining were used to observe the histopathological features of lung. airway hyperresponsiveness (AHR) was detected by ventilator; The expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and E-cadherin in the lungs was evaluated by IHC. The concentrations of Mucin5AC (MUC5AC), eotaxin, IL-4, IL-5, IL-9, IL-13, interferon (IFN)-γ, IL-6, IL-8, IL-17A, IL-33, IL-25, thymic stromal lymphopoietin (TSLP), monocyte chemoattractant protein 1 (MCP-1), leukotriene (LT) B₄, LTC₄, LTD₄, LTE₄ in bronchoalveolar lavage fluid (BALF) and total IgE (tIgE), OVA-Specific IgE (OVA-IgE) in serum were measured by ELISA. ILC2s and eosinophils were detected in lung tissue by flow cytometry. The gene expression levels of IL-33 and ST2 were detected by RT-qPCR.

Results: Administration of TA reduced pulmonary inflammatory symptoms, MUC5AC production in the BALF, and AHR. At the same time, TA inhibited eotaxin production and eosinophil recruitment. Moreover, TA significantly decreased Th2 and Th17 cytokines and increased Th1 cytokines, contributing to restore the balance between Th1 and Th2 and Th17 cytokines. TA may reduce ILC2s numbers by inhibiting IL-33, IL-25, and TSLP levels in BALF and IL-33/ST2 signaling in lung tissue. Finally, TA decreased tIgE, OVA-IgE, and MCP-1 levels and subsequently inhibited mast cell activation and leukotriene release.

Conclusions: These findings imply that TA may be an effective immunoregulatory medication for the management and prevention of asthma.

Keywords: Airway inflammation; Alstonia scholaris (L.) R. Br.; Asthma; Th2 cytokines; Total alkaloids.