Sinigrin Enhanced Antiasthmatic Effects of Beta Adrenergic Receptors Agonists by Regulating cAMP-Mediated Pathways.

Simeng Chu,Wenjuan Liu,Menglin Yan,Yingying Guo,Min Jiang,Nianwei Chang,Yujie Lu,Gang Bai

doi:10.3389/fphar.2020.00723

Abstract

Millions of patients suffer from asthma worldwide. However, the first-line drugs used to treat asthma, namely, the beta-adrenergic receptors agonists (β-agonists), are not recommended for use as monotherapy because of their severe dose-related side effects. This limitation has prompted the search for new therapies, which can be used in conjunction with β--agonists so that lower doses can be administered. Sinigrin is a major compound found in many antiasthmatic medicinal plants. In this study, we explored the antiasthmatic activity of sinigrin when used in combination with β-agonists and its underlying mechanism. Sinigrin enhanced the asthma-relieving effects of isoproterenol and reduced the effective isoproterenol dose in an acute-asthma model in guinea pigs. Mechanistically, sinigrin enhanced the cAMP levels induced by β-agonists by inhibiting PDE4. The resulting increase in cAMP levels stimulated the activity of the downstream effector protein kinase A, which would be expected to ultimately induce the relaxation of airway smooth muscle. In conclusion, sinigrin enhances the asthma-relieving effects of β-agonists by regulating the cAMP signaling pathway and represents a potential add-on drug to β-agonists for the treatment of asthma.

Highlights

Asthma is a chronic inflammatory airway disease (Lowhagen, 2015) that affects millions of patients worldwide
The process of drug inhalation localizes the effect of drug to lung tissue, in particular concentrating the therapeutic effect on the airway smooth muscles, while minimizing distribution of the drug to the systemic circulation
Acute bronchoconstriction leading to difficulty in breathing is a clear symptom of asthma (Billington et al, 2013; Dekkers et al, 2013)

Summary

Introduction

Asthma is a chronic inflammatory airway disease (Lowhagen, 2015) that affects millions of patients worldwide. Asthma therapy includes the use of inhalable corticosteroids (ICSs), anticholinergic drugs, and beta-2 adrenergic receptor agonists (BAs) (Lommatzsch and Virchow, 2014; Castillo et al, 2017; Suissa et al, 2017). Sinigrin in Treatment of Asthma side effects include ketoacidosis (Philipson, 2002), hypokalemia (Scheinin et al, 1987), and dose-related tremors (Cazzola et al, 2005). Those adverse effects can lead to an increased risk of exacerbating asthma. Long-acting beta-2 adrenergic receptor agonists are not recommended for use in monotherapy for the treatment of asthma (Al-Sajee et al, 2019)

Methods

Results

Conclusion