{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:12:41Z","timestamp":1790431961257,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Unit of Excellence in Research and Product Development of Coffee, University of Phayao","award":["UoE64002"],"award-info":[{"award-number":["UoE64002"]}]},{"name":"The NSTDA Chair Professor Grant (the Fourth Grant) of the Crown Property Bureau and the Na-tional Science and Technology Development Agency","award":["The Fourth Grant"],"award-info":[{"award-number":["The Fourth Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Antispasmodic agents are used for modulating gastrointestinal motility. Several compounds isolated from terrestrial plants have antispasmodic properties. This study aimed to explore the inhibitory effect of the pyrrolidine derivative, asperidine B, isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178, on spasmodic activity. Isolated rat ileum was set up in an organ bath. The contractile responses of asperidine B (0.3 to 30 \u00b5M) on potassium chloride and acetylcholine-induced contractions were recorded. To investigate its antispasmodic mechanism, CaCl2, acetylcholine, N\u03c9-nitro-l-arginine methyl ester (l-NAME), nifedipine, methylene blue and tetraethylammonium chloride (TEA) were tested in the absence or in the presence of asperidine B. Cumulative concentrations of asperidine B reduced the ileal contraction by ~37%. The calcium chloride and acetylcholine-induced ileal contraction was suppressed by asperidine B. The effects of asperidine B combined with nifedipine, atropine or TEA were similar to those treated with nifedipine, atropine or TEA, respectively. In contrast, in the presence of l-NAME and methylene blue, the antispasmodic effect of asperidine B was unaltered. These results suggest that the antispasmodic property of asperidine B is probably due to the blockage of the L-type Ca2+ channel and is associated with K+ channels and muscarinic receptor, possibly by affecting non-selective cation channels and\/or releasing intracellular calcium.<\/jats:p>","DOI":"10.3390\/molecules26185492","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T21:36:58Z","timestamp":1631223418000},"page":"5492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Antispasmodic Effect of Asperidine B, a Pyrrolidine Derivative, through Inhibition of L-Type Ca2+ Channel in Rat Ileal Smooth Muscle"],"prefix":"10.3390","volume":"26","author":[{"given":"Acharaporn","family":"Duangjai","sequence":"first","affiliation":[{"name":"Unit of Excellence in Research and Product Development of Coffee, Division of Physiology, School of Medical Sciences, University of Phayao, Mueang Phayao, Phayao 56000, Thailand"},{"name":"Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Mueang Phayao, Phayao 56000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vatcharin","family":"Rukachaisirikul","sequence":"additional","affiliation":[{"name":"Division of Physical Science and Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaowapa","family":"Sukpondma","sequence":"additional","affiliation":[{"name":"Division of Physical Science and Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5537-1023","authenticated-orcid":false,"given":"Chutima","family":"Srimaroeng","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Chiang Mai University, Mueang Chiang Mai, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chatchai","family":"Muanprasat","sequence":"additional","affiliation":[{"name":"Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangphli, Samutprakarn 10540, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"key":"ref_1","first-page":"3819714","article-title":"Natural antispasmodics: Source, stereochemical configuration, and biological activity","volume":"2018","author":"Bach","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1159\/000092876","article-title":"Gastrointestinal motility disorders: An update","volume":"24","author":"Lacy","year":"2006","journal-title":"Dig. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1365-2982.2008.01108.x","article-title":"Regulation of smooth muscle excitation and contraction","volume":"20","author":"Sanders","year":"2008","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1440-1681.2005.04222.x","article-title":"New insights into beta-adrenoceptors in smooth muscle: Distribution of receptor subtypes and molecular mechanisms triggering muscle relaxation","volume":"32","author":"Tanaka","year":"2005","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1152\/jn.2002.87.6.2643","article-title":"Acetylcholine increases intracellular Ca2+ in taste cells via activation of muscarinic receptors","volume":"87","author":"Ogura","year":"2002","journal-title":"J. Neurophysiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/S0005-2728(99)00024-9","article-title":"Guanylate cyclase and the NO\/cGMP signaling pathway","volume":"1411","author":"Denninger","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1007\/BF02974628","article-title":"Studies on the effects of piperidine derivatives on blood pressure and smooth muscles contractions","volume":"21","author":"Saeed","year":"1998","journal-title":"Arch. Pharm. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/BF02977465","article-title":"Synthesis and smooth muscle-selective relaxant activity of a piperidine analogue: 1-(4\u2032-fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride","volume":"29","author":"Taqvi","year":"2006","journal-title":"Arch. Pharm. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1527-3458.2008.00044.x","article-title":"Tolperisone: A typical representative of a class of centrally acting muscle relaxants with less sedative side effects","volume":"14","author":"Quasthoff","year":"2008","journal-title":"CNS Neurosci. Ther."},{"key":"ref_10","first-page":"28","article-title":"The investigation of the action mechanism of ammonium pyrrolodine dithiocarbamate on rat bladder smooth muscle contraction-relxation response","volume":"45","author":"Yilmaz","year":"2020","journal-title":"JSR-A"},{"key":"ref_11","first-page":"50","article-title":"The investigation of the action mechanism of ammonium pyrrolidine dithiocarbamate on rat aorta smooth muscle contraction-relaxation responses","volume":"45","author":"Yilmaz","year":"2020","journal-title":"JSR-A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"152078","DOI":"10.1016\/j.tetlet.2020.152078","article-title":"Asperidine B: Total synthesis and structure correction","volume":"61","author":"Waddell","year":"2020","journal-title":"Tetrahedron Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/aps.2009.98","article-title":"High K+-induced contraction requires depolarization-induced Ca2+ release from internal stores in rat gut smooth muscle","volume":"30","author":"Kirschstein","year":"2009","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1146\/annurev.physiol.68.040504.094707","article-title":"Signaling for contraction and relaxation in smooth muscle of the gut","volume":"68","author":"Murthy","year":"2006","journal-title":"Annu. Rev. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tanahashi, Y., Komori, S., Matsuyama, H., Kitazawa, T., and Unno, T. (2021). Functions of muscarinic receptor subtypes in gastrointestinal smooth muscle: A review of studies with receptor-knockout mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020926"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/sj.bjp.0705267","article-title":"Receptor signaling mechanisms underlying muscarinic agonist-evoked contraction in guinea-pig ileal longitudinal smooth muscle","volume":"139","author":"Unno","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.bcp.2005.03.009","article-title":"Muscarinic subtype affinity and functional activity profile of 1-methyl-2-(2-methyl-1, 3-dioxolan-4-yl) pyrrolidine and 1-methyl-2-(2-methyl-1, 3-oxathiolan-5-yl) pyrrolidine derivatives","volume":"69","author":"Dei","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1021\/jm9905155","article-title":"Pyrrolidine inhibitors of human cytosolic phospholipase A2","volume":"43","author":"Seno","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"34519","DOI":"10.1074\/jbc.273.51.34519","article-title":"Differential regulation of phospholipase A2 (PLA2)-dependent Ca2+ signaling in smooth muscle by cAMP-and cGMP-dependent protein kinases: Inhibitory phosphorylation of PLA2 by cyclic nucleotide-dependent protein kinases","volume":"273","author":"Murthy","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/sj.bjp.0704954","article-title":"The intracellular pathway of the acetylcholine-induced contraction in cat detrusor muscle cells","volume":"137","author":"An","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1006\/phrs.2002.0950","article-title":"The reactivity of serotonin, acetylcholine and kcl-induced contractions to relaxant agents in the rat gastric fundus","volume":"45","author":"Akar","year":"2002","journal-title":"Pharmacol. Res."},{"key":"ref_22","first-page":"429","article-title":"Potassium channel modulation: A new drug principle for regulation of smooth muscle contractility. Studies on isolated airways and arteries","volume":"43","year":"1996","journal-title":"Dan. Med. Bull."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1046\/j.1365-2680.2000.00183.x","article-title":"Potassium channels in gastrointestinal smooth muscle","volume":"20","author":"Vogalis","year":"2000","journal-title":"J. Auton. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1085\/jgp.78.1.87","article-title":"Effects of tetraethylammonium on potassium currents in a molluscan neurons","volume":"78","author":"Hermann","year":"1981","journal-title":"J. Gen. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1529\/biophysj.104.046664","article-title":"The external TEA binding site and C-type inactivation in voltage-gated potassium channels","volume":"87","author":"Andalib","year":"2004","journal-title":"Biophys. J."},{"key":"ref_26","first-page":"315","article-title":"Contraction and relaxation signaling in gastrointestinal smooth muscle","volume":"5","year":"2018","journal-title":"ECGDS"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1021\/acs.jnatprod.5b00961","article-title":"Lovastatin analogues from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178","volume":"79","author":"Phainuphong","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4502","DOI":"10.1016\/j.bmc.2018.07.036","article-title":"Asperidines A\u2013C, pyrrolidine and piperidine derivatives from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178","volume":"26","author":"Phainuphong","year":"2018","journal-title":"Bioorg. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/18\/5492\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:59:46Z","timestamp":1760165986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/18\/5492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,9]]},"references-count":28,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["molecules26185492"],"URL":"https:\/\/doi.org\/10.3390\/molecules26185492","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,9]]}}}