{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T19:35:52Z","timestamp":1781120152513,"version":"3.54.1"},"reference-count":57,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u00b5M)-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 \u00b5M)-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 \u00b5M)-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.<\/jats:p>","DOI":"10.3390\/molecules26216348","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:31:26Z","timestamp":1634765486000},"page":"6348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Spasmolytic, Bronchodilator, and Vasodilator Activities of Parmotrema perlatum Are Explained by Anti-Muscarinic and Calcium Antagonistic Mechanisms"],"prefix":"10.3390","volume":"26","author":[{"given":"Musaddique","family":"Hussain","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, The Islamia University of Bahawulpur, Bahawulpur 63100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazoor","family":"Bakhsh","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Bahauddin Zakariya University, Multan 66000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9412-9897","authenticated-orcid":false,"given":"Shahzada Khurram","family":"Syed","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, School of Health Sciences, University of Management and Technology, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik Saad","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Government College University, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2240-4757","authenticated-orcid":false,"given":"Ali M.","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4017-8754","authenticated-orcid":false,"given":"Taha","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5073-2088","authenticated-orcid":false,"given":"Afaf A.","family":"Aldahish","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-2272","authenticated-orcid":false,"given":"Talha Bin","family":"Emran","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashif Ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, The Islamia University of Bahawulpur, Bahawulpur 63100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid Hussain","family":"Janbaz","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Bahauddin Zakariya University, Multan 66000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1016\/S0140-6736(16)31593-8","article-title":"Global, regional, and national causes of under-5 mortality in 2000\u201315: An updated systematic analysis with implications for the Sustainable Development Goals","volume":"388","author":"Liu","year":"2016","journal-title":"Lancet"},{"key":"ref_2","unstructured":"UNICEF, One Is too Many Ending Child Deaths from Pneumonia and Diarrhoea. Available online: https:\/\/www.unicef.org\/publications\/index_93020.html."},{"key":"ref_3","first-page":"180","article-title":"Acute diarrhea in adults","volume":"89","author":"Barr","year":"2014","journal-title":"Am. Fam. Physician"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/S0140-6736(17)33311-1","article-title":"Seminar Asthma","volume":"391","author":"Papi","year":"2018","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S2213-2600(20)30363-5","article-title":"The genetics of asthma and the promise of genomics-guided drug target discovery","volume":"8","author":"Gosens","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/ajh.2009.103","article-title":"Prognostic Value of Different Indices of Blood Pressure Variability in Hypertensive Patients","volume":"22","author":"Pierdomenico","year":"2009","journal-title":"Am. J. Hypertens."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/nrneph.2015.172","article-title":"Hypertension-attributed nephropathy: What\u2019s in a name?","volume":"12","author":"Freedman","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_8","first-page":"121","article-title":"Alternative and Complementary Medicine for Preventing and Treating Cardiovascular Disease","volume":"55","author":"Frishman","year":"2009","journal-title":"Disease"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.phymed.2010.08.016","article-title":"Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: Comparison with Captopril","volume":"18","author":"Susalit","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"30","DOI":"10.4103\/0973-7847.79097","article-title":"Role of natural herbs in the treatment of hypertension","volume":"5","author":"Tabassum","year":"2011","journal-title":"Pharmacogn. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jep.2005.01.017","article-title":"Studies on the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the Carumcopticum seed extract","volume":"98","author":"Gilani","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1472-8206.2007.00561.x","article-title":"Gastrointestinal, selective airways and urinary bladder relaxant effects of Hyoscyamusniger are mediated through dual blockade of muscarinic receptors and Ca2+channels","volume":"22","author":"Gilani","year":"2008","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.lfs.2003.06.039","article-title":"Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta","volume":"74","author":"Ajay","year":"2003","journal-title":"Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1152\/physrev.1979.59.3.606","article-title":"Mechanisms of action of transmitters and other substances on smooth muscle","volume":"59","author":"Bolton","year":"1979","journal-title":"Physiol. Rev."},{"key":"ref_15","first-page":"115","article-title":"Bronchodilator, spasmolytic and calcium antagonist activities of Nigella sativa seeds (Kalonji): A traditional herbal product with multiple medicinal uses","volume":"51","author":"Gilani","year":"2001","journal-title":"J. Pak. Med. Assoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/ptr.4821","article-title":"Studies on Prokinetic, Laxative and Spasmodic Activities of Phyllanthus emblica in Experimental Animals","volume":"27","author":"Mehmood","year":"2013","journal-title":"Phytotherapy Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.jep.2016.09.028","article-title":"Anti-cholinergic and Ca2+-antagonist mechanisms explain the pharmacological basis for folkloric use of Sisymbriumirio Linn. in gastrointestinal, airways and vascular system ailments","volume":"193","author":"Hussain","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jep.2011.09.019","article-title":"Gastrointestial and respiratory activities of Acacia leucophloea","volume":"138","author":"Imran","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","first-page":"a004549","article-title":"Calcium Signaling in Smooth Muscle","volume":"3","author":"Werner","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"167S","DOI":"10.1186\/1297-9686-26-S1-S167","article-title":"Rabbit and man: Genetic and historic approach","volume":"26","author":"Monnerot","year":"1994","journal-title":"Genet. Sel. Evol."},{"key":"ref_21","unstructured":"Khare, C.P. (2004). Indian Medicinal Plants: An Illustrated Dictionary, Springer Science & Business Media."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1007\/BF02866567","article-title":"Parmelia spp. (lichens) in ancient medicinal plant lore of India","volume":"55","author":"Kaushal","year":"2001","journal-title":"Econ. Bot."},{"key":"ref_23","first-page":"173","article-title":"Two New Terpenes from the Lichen Parmeliaperlata","volume":"38","author":"Abdullah","year":"2007","journal-title":"Indian J. Chem."},{"key":"ref_24","first-page":"101","article-title":"Phytochemical investigation of therapeutic important lichen: Parmeliaperlata","volume":"2","author":"Sharma","year":"2012","journal-title":"J. Nat. Prod. Plant Resour."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/9781119946045.ch38","article-title":"Manganese, Molybdenum, Boron, Chromium, and Other Trace Elements","volume":"18","author":"Nielsen","year":"2012","journal-title":"Present Knowl. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s002530100684","article-title":"Pharmaceutically relevant metabolites from lichens","volume":"56","year":"2001","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1023\/B:BICO.0000009378.31023.ba","article-title":"Antifungal activity of lichen extracts and lichenic acids","volume":"49","author":"Halama","year":"2004","journal-title":"BioControl"},{"key":"ref_28","first-page":"43","article-title":"Antidiabetic and antihyperlipidemic effect of Parmeliaperlata. Ach. in alloxan induced diabetic rats","volume":"6","author":"Jothi","year":"2014","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"70","DOI":"10.7324\/JAPS.2014.40212","article-title":"Hepatoprotective activity of Parmeliaperlata (Huds.) Ach. against CCl4 induced liver toxicity in Albino Wistar rats","volume":"4","author":"Shailajan","year":"2014","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1078\/094471103322331458","article-title":"Cytotoxic activity of some lichen extracts on murine and human cancer cell lines","volume":"10","author":"Tomasi","year":"2003","journal-title":"Phytomedicine"},{"key":"ref_31","first-page":"7","article-title":"In Vitro Studies on Antioxidant, Hypolipidemic and Cytotoxic Potential of ParmeliaPerlata","volume":"2","author":"Rahman","year":"2014","journal-title":"Am. J. Life Sci."},{"key":"ref_32","first-page":"129","article-title":"Evaluation of antiurolithiatic effects of Parmeliaperlata against calcium oxalate calculi in hyperoxaluric rats","volume":"8","author":"Goyal","year":"2018","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1007\/s11694-020-00672-1","article-title":"Determination of chemical composition and antimicrobial, antioxidant and cytotoxic activities of lichens Parmeliaconspersa and Parmeliaperlata","volume":"15","year":"2021","journal-title":"J. Food Meas. Charact."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.31254\/phyto.2013.2604","article-title":"Gastroprotective effect of ethanolic extract of Parmeliaperlata in rats","volume":"2","author":"Lakshmi","year":"2013","journal-title":"J. Phytopharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1002\/jsfa.5559","article-title":"Agriculture, Antioxidant, antimicrobial and anticancer activities of three Parmelia species","volume":"92","year":"2012","journal-title":"J. Sci. Food Agric."},{"key":"ref_36","first-page":"47","article-title":"Evaluation of antimicrobial prospective of Parmotremaperlatum hexane extract","volume":"4","author":"Hoda","year":"2015","journal-title":"Int. J. Pharm. Res. Allied Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.toxrep.2019.11.003","article-title":"Anticholinergic and antioxidant activities of usnic acid-an activity-structure insight","volume":"6","author":"Cakmak","year":"2019","journal-title":"Toxicol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17715","DOI":"10.1021\/acsomega.0c02306","article-title":"Is Usnic Acid a Promising Radical Scavenger?","volume":"5","author":"Hoa","year":"2020","journal-title":"ACS Omega"},{"key":"ref_39","first-page":"13","article-title":"Innovation, An antioxidant and bioactive compound studies of Parmeliaperlata, Ganoderma lucidum and Phellinus igniarius\u2013supplimentory drug","volume":"2","author":"Paul","year":"2014","journal-title":"Asian J. Pharm. Technol. Innov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"C769","DOI":"10.1152\/ajpcell.00529.2004","article-title":"Regulation of smooth muscle calcium sensitivity: KCl as a calcium-sensitizing stimulus","volume":"288","author":"Ratz","year":"2005","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3390\/60300142","article-title":"Muscarinic receptor agonists and antagonists","volume":"6","author":"Broadley","year":"2001","journal-title":"Molecules"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/S0140-6736(04)17025-6","article-title":"Prospects for new drugs for chronic obstructive pulmonary disease","volume":"364","author":"Barnes","year":"2004","journal-title":"Lancet"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1513\/pats.200704-047VS","article-title":"Calcium Signaling in Airway Smooth Muscle","volume":"5","author":"Jude","year":"2008","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fcimb.2020.00009","article-title":"The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks","volume":"10","author":"Enaud","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_45","unstructured":"Gayton, A.C., and Hall, J.E. (2006). Text. Book of Medical Physiology, WBSaunders. [11th ed.]."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1007\/s10620-005-2957-2","article-title":"Pharmacological Basis for the Medicinal Use of Ginger in Gastrointestinal Disorders","volume":"50","author":"Ghayur","year":"2005","journal-title":"Dig. Dis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.bcp.2006.09.010","article-title":"Structure\u2013function of \u03b11-adrenergic receptors","volume":"73","author":"Perez","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S0306-3623(97)00002-5","article-title":"Depolarization-dependent effect of flavonoids in rat uterine smooth muscle contraction elicited by CaCl2","volume":"29","author":"Revuelta","year":"1997","journal-title":"Gen. Pharmacol. Vasc. Syst."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.fitote.2017.11.006","article-title":"3-Arylisoindolinone and sesquiterpene derivatives from the mangrove endophytic fungi Aspergillus versicolor SYSU-SKS025","volume":"124","author":"Cui","year":"2018","journal-title":"Fitoterapia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jep.2005.06.001","article-title":"Trends in ethnopharmacology","volume":"100","author":"Gilani","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.apjtm.2017.10.021","article-title":"Pharmacological evaluation of smooth muscle relaxant and cardiac-modulation potential of Phyla nodiflora in ex-vivo and in-vivo experiments","volume":"10","author":"Rahman","year":"2017","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_52","unstructured":"National Research Council (2010). Guide for the Care and Use of Laboratory Animals, The National Academies Press."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jep.2017.11.006","article-title":"Dual mechanisms of anti-muscarinic and Ca++ antagonistic activities to validate the folkloric uses of Cyperusniveus Retz. as antispasmodic and antidiarrheal","volume":"213","author":"Aleem","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jpba.2010.04.013","article-title":"HPLC isolation of antioxidant constituents from Xanthoparmelia spp.","volume":"53","author":"Raggio","year":"2010","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_55","first-page":"3","article-title":"Classical Approaches to the Study of Drug\u00d2 Receptor Interactions","volume":"2","author":"Jenkinson","year":"2002","journal-title":"Textb. Recept. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.jep.2009.09.010","article-title":"Antispasmodic and bronchodilator activities of Artemisia vulgaris are mediated through dual blockade of muscarinic receptors and calcium influx","volume":"126","author":"Khan","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1111\/j.1476-5381.2010.00863.x","article-title":"Elusive equilibrium: The challenge of interpreting receptor pharmacology using calcium assays","volume":"161","author":"Charlton","year":"2010","journal-title":"Br. J. Pharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6348\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:19:37Z","timestamp":1760167177000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":57,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["molecules26216348"],"URL":"https:\/\/doi.org\/10.3390\/molecules26216348","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]}}}