Tylophora indica (Burm. f.) Merr alleviates tracheal smooth muscle hyperresponsiveness in ovalbumin-induced allergic-asthma model in guinea-pigs: Evidences from ex vivo, in silico and in vivo studies.

Abstract

Tylophora indica (Burm. f.) Merr is a climbing perennial plant reported in Indian traditional system of medicine for its use in allergy and asthma. However, only few scientific studies have been performed in the past to validate its antiasthmatic potential. The present study deals with investigation of airway smooth muscle relaxant and antiasthmatic potential of extract and subsequent fractions prepared from T.indica. The most active fraction of T.indica leaves selected through bio-guided activity was subjected to liquid chromatography-mass spectrometry (LC-MS) analysis for chemical profiling. The binding affinity of identified compounds in fraction towards M3 and H1 receptors was determined by molecular docking study. F-2 (chloroform fraction prepared from methanolic extract of T.indica leaves) was examined for its smooth muscle relaxant properties using isolated trachea of guinea-pig. Further, F-2 was evaluated through in vivo studies employing ovalbumin-induced asthma model in guinea-pigs. F-2 was found most effective in bioassay-guided fractionation. Characterization by LC-MS analysis revealed presence of five major bioactive compounds in F-2 that showed good docking interactions with M3 and H1 receptors. The ex vivo study demonstrated that F-2 could significantly relax tracheal rings via targeting multiple signalling pathways videlicet, namely, noncompetitive antagonism of the histamine and muscarinic receptors, β2-adrenergic stimulation and activation of soluble guanylyl cyclase. In in vivo studies, F-2 ameliorated airway hyperresponsiveness and decreased broncho alveolar lavage fluid (BALF) levels of inflammatory cytokines and immunoglobulin E (IgE). These results confirm the traditional use of T.indica as an antiasthmatic agent which are evidenced through ex vivo, in silico and in vivo studies.