Abstract

Parmotremaperlatum is traditionally used in different areas of Pakistan to treat gastrointestinal, respiratory, and vascular diseases. This study evaluates the underlying mechanisms for traditional uses of P. perlatum in diarrhea, asthma, and hypertension. In vitro pharmacological studies were conducted using isolated jejunum, trachea, and aortic preparations, while the cytotoxic study was conducted in mice. Crude extract of P. perlatum(Pp.Cr), comprising appreciable quantities of alkaloids and flavonoids, relaxed spontaneously contracting jejunum preparation, K+ (80 mM)-induced, and carbachol (1 µM)-induced jejunum contractions in a concentration-dependent manner similar to dicyclomine and dantrolene. Pp.Cr showed a rightward parallel shift of concentration-response curves (CRCs) of Cch after a non-parallel shift similarto dicyclomine and shifted CRCs of Ca+2 to rightward much likeverapamil and dantrolene, demonstrating the coexistence of antimuscarinic and Ca+2 antagonistic mechanism. Furthermore, Pp.Cr, dicyclomine, and dantrolene relaxed K+ (80 mM)-induced and Cch (1 µM)-induced tracheal contractions and shifted rightward CRCs of Cch similar to dicyclomine, signifying the dual blockade. Additionally, Pp.Cr also relaxed the K+ (80 mM)-induced and phenylephrine (1 µM)-induced aortic contraction, similarly to verapamil and dantrolene, suggesting Ca+2 channel antagonism. Here, we explored for the first time thespasmolytic and bronchodilator effects of Pp.Crand whether they maybe due to the dual blockade of Ca+2 channels and muscarinic receptors, while the vasodilator effect might be owing to Ca+2 antagonism. Our results provide the pharmacological evidence that P. perlatum could be a new potential therapeutic option to treat gastrointestinal, respiratory, and vascular diseases. Hence, there is a need for further research to explore bioactive constituent of P. perlatum as well as further investigation by suitable experimental models are required to further confirm the importance and usefulness of P. perlatum in diarrhea, asthma, and hypertension treatment.

Highlights

  • Diarrhea is a common gastrointestinal problem characterized by the loss of watery stool often with vomiting and fever, and mild to severe life-threatening dehydration.Dehydration is especially hazardous in children, the elderly, and people with weaker immune systems if left untreated

  • P. perlatumhas been traditionally used for the treatment of diarrhea, bronchitis, asthma, airway congestion, and hypertension. This project was designed to authenticate the folkloric uses of P. perlatumas well as to investigate the possible basic mechanism(s) of action

  • P. perlatum has been traditionally used for the treatment of diarrhea, bronchitis, asthma, airway congestion, and hypertension

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Summary

Introduction

Diarrhea is a common gastrointestinal problem characterized by the loss of watery stool often with vomiting and fever, and mild to severe life-threatening dehydration.Dehydration is especially hazardous in children, the elderly, and people with weaker immune systems if left untreated. Diarrhea is a common gastrointestinal problem characterized by the loss of watery stool often with vomiting and fever, and mild to severe life-threatening dehydration. Diarrhea causes approximately 4–5 million deaths annually throughout the world and 80% of these deaths are reported in developing countries [1,2]. Non-communicable respiratory illness that affects both children and adults and is characterized by a wide range of respiratory symptoms and airflow limitations [4]. Asthma is caused by complex gene–environment interactions, resulting in a wide range of clinical manifestations as well as the kind and severity of airway inflammation and remodeling [5]. People with under-treated asthma can suffer sleep disturbance, tiredness during the day, and poor concentration. Leukotriene antagonists, short- and long-acting bronchodilators, anticholinergic agents, anti-IL4 and IL-5 treatments, anti-IgE antibody and combination therapies (including inhaled corticosteroid, long-acting bronchodilator, and anti-muscarinic agent) are all common asthma treatments, but the symptoms of asthma are not adequately controlled with currently available therapy

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