PMID- 37354029 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20231127 IS - 1472-8206 (Electronic) IS - 0767-3981 (Linking) VI - 37 IP - 6 DP - 2023 Dec TI - 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. PG - 1153-1169 LID - 10.1111/fcp.12927 [doi] AB - BACKGROUND: 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. OBJECTIVES: The present study deals with investigation of airway smooth muscle relaxant and antiasthmatic potential of extract and subsequent fractions prepared from T. indica. METHODS: 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 M(3) and H(1) 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. RESULTS: 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 M(3) and H(1) 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, beta2-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). CONCLUSION: 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. CI - (c) 2023 Societe Francaise de Pharmacologie et de Therapeutique. Published by John Wiley & Sons Ltd. FAU - Gururani, Ritika AU - Gururani R AD - Department of Pharmacy, Banasthali Vidyapith, Banasthali, India. FAU - Patel, Saraswati AU - Patel S AD - Department of Pharmacy, Banasthali Vidyapith, Banasthali, India. FAU - Bisht, Akansha AU - Bisht A AD - Department of Pharmacy, Banasthali Vidyapith, Banasthali, India. FAU - Jain, Smita AU - Jain S AD - Department of Pharmacy, Banasthali Vidyapith, Banasthali, India. FAU - Paliwal, Sarvesh AU - Paliwal S AD - Department of Pharmacy, Banasthali Vidyapith, Banasthali, India. FAU - Dwivedi, Jaya AU - Dwivedi J AUID- ORCID: 0000-0002-1524-7714 AD - Department of Chemistry, Banasthali Vidyapith, Banasthali, India. FAU - Sharma, Swapnil AU - Sharma S AUID- ORCID: 0000-0003-2639-7096 AD - Department of Pharmacy, Banasthali Vidyapith, Banasthali, India. LA - eng PT - Journal Article DEP - 20230624 PL - England TA - Fundam Clin Pharmacol JT - Fundamental & clinical pharmacology JID - 8710411 RN - 9006-59-1 (Ovalbumin) RN - 0 (Anti-Asthmatic Agents) SB - IM MH - Animals MH - Guinea Pigs MH - Ovalbumin MH - Tylophora MH - Molecular Docking Simulation MH - *Asthma/drug therapy/chemically induced MH - Muscle, Smooth/physiology MH - *Anti-Asthmatic Agents/pharmacology MH - Trachea/physiology OTO - NOTNLM OT - H1 receptor OT - M3 receptor OT - asthma OT - molecular docking OT - tracheal smooth muscle relaxant EDAT- 2023/06/24 11:42 MHDA- 2023/11/27 12:42 CRDT- 2023/06/24 05:33 PHST- 2023/05/23 00:00 [revised] PHST- 2022/12/30 00:00 [received] PHST- 2023/06/05 00:00 [accepted] PHST- 2023/11/27 12:42 [medline] PHST- 2023/06/24 11:42 [pubmed] PHST- 2023/06/24 05:33 [entrez] AID - 10.1111/fcp.12927 [doi] PST - ppublish SO - Fundam Clin Pharmacol. 2023 Dec;37(6):1153-1169. doi: 10.1111/fcp.12927. Epub 2023 Jun 24.