Common Plant May Serve as New Source of More Effective Asthma Therapy

An international team of scientists says they have extracted a new type of active pharmaceutical ingredient from coralberry leaves that might serve as a novel treatment for asthma. The leaves contain a substance named FR900359 and it inhibited the contraction of the airways in mice.

Their study (“Targeted Inhibition of G_q Signaling Induces Airway Relaxation in Mouse Models of Asthma”) is published in Science Translational Medicine. 

“We…hypothesized that pharmacological G_q inhibition could serve as a central mechanism to achieve efficient therapeutic bronchorelaxation. We found that the compound FR900359 (FR), a membrane-permeable inhibitor of G_q, was effective in silencing G_q signaling in murine and human airway smooth muscle cells. Moreover, FR both prevented bronchoconstrictor responses and triggered sustained airway relaxation in mouse, pig, and human airway tissue ex vivo,” write the investigators. “Inhalation of FR in healthy wild-type mice resulted in high local concentrations of the compound in the lungs and prevented airway constriction without acute effects on blood pressure and heart rate. FR administration also protected against airway hyperreactivity in murine models of allergen sensitization using ovalbumin and house dust mite as allergens. Our findings establish FR as a selective G_q inhibitor when applied locally to the airways of mice in vivo and suggest that pharmacological blockade of G_q proteins may be a useful therapeutic strategy to achieve bronchorelaxation in asthmatic lung disease.”

Researchers at the Institutes of Physiology I, Pharmaceutical Biology, and Pharmaceutical Chemistry at the University of Bonn, and asthma specialists from Nottingham in the U.K., report that FR appears to be more effective and has a more prolonged method of action in relieving bronchial spasms than salbutamol. 

“We have so far only tested the substance in asthmatic mice,” explains junior professor Daniela Wenzel, Dr. med., who is the study leader doing research in respiratory diseases at the Institute of Physiology I at the University of Bonn. “This compound inhibits critical signaling molecules in our cells, the G_q proteins,” which are involved in key functions in many processes in the body, including control of the airway tone.

Normally, interaction of various signaling pathways induces narrowing of the airways. Inhibition of individual signaling pathways can reduce the contraction of the respiratory tract. However, this does not make it possible to completely prevent such contractions in patients with severe asthma, says Dr. Wenzel. The various contracting signals converge on G_q proteins and trigger airway spasm. “When we inhibit the activation of G_q proteins with FR900359, we achieve a much greater effect,” adds Michaela. Matthey from the Institute of Physiology I.

“We were able to prevent the animals from reacting to allergens such as house dust mite with a narrowing of the bronchia,” points out Dr. Wenzel, noting that there were few side effects, as FR could be applied via inhalation to the respiratory tract and thus only reached the systemic circulation in small quantities. However, it is not known whether the substance is also suitable for use in people and additional research is needed.