{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T10:13:50Z","timestamp":1778667230276,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Dysmenorrhea is one of the most prevalent disorders in gynecology. Historically, adlay (Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been explored for its anti-tumor, pain relief, anti-inflammatory, and analgesic effects. The aim of this study was to evaluate the effects of adlay seeds on the inhibition of uterine contraction and thus dysmenorrhea relief, in vitro and in vivo. HPLC-MS and GC were used to elucidate the ethyl acetate fraction of adlay testa ethanolic extract (ATE-EA) and ethyl acetate fraction of adlay hull ethanolic extract (AHE-EA). Elucidation yielded flavonoids, phytosterols, and fatty acids. Uterine leiomyomas and normal adjacent myometrial tissue were evaluated by oxytocin- and PG-induced uterine contractility. ATE-EA and AHE-EA suppressed uterine contraction induced by prostaglandin F2 alpha (PGF2\u03b1), oxytocin, carbachol, and high-KCl solution ex vivo. In addition, the external calcium (Ca2+) influx induced contraction, and increased Ca2+ concentration was inhibited by ATE-EA and AHE-EA on the uterine smooth muscle of rats. Furthermore, ATE-EA and AHE-EA effectively attenuated the contraction of normal human myometrium tissues more than adjacent uterine leiomyoma in response to PGF2\u03b1. 3,5,6,7,8,3\u2032,4\u2032-Heptamethoxyflavone and chrysoeriol produced a remarkable inhibition with values of IC50 = 24.91 and 25.59 \u00b5M, respectively. The experimental results showed that treatment with ATE-EA at 30 mg\/day effectively decreased the writhing frequency both on the oxytocin-induced writhing test and acetic acid writhing test of the ICR mouse.<\/jats:p>","DOI":"10.3390\/biom11060887","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T11:00:33Z","timestamp":1623754833000},"page":"887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Ethanolic Extracts of Adlay Testa and Hull and Their Active Biomolecules Exert Relaxing Effect on Uterine Muscle Contraction through Blocking Extracellular Calcium Influx in Ex Vivo and In Vivo Studies"],"prefix":"10.3390","volume":"11","author":[{"given":"Yun-Ju","family":"Huang","sequence":"first","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chieh","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Fen","family":"Chiang","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9675-6691","authenticated-orcid":false,"given":"Mohamed","family":"Ali","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenchang","family":"Chiang","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2689-9101","authenticated-orcid":false,"given":"Cheng-Pei","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2888-2618","authenticated-orcid":false,"given":"Shih-Min","family":"Hsia","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"School of Food Safety, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1093\/epirev\/mxt009","article-title":"The prevalence and risk factors of dysmenorrhea","volume":"36","author":"Ju","year":"2014","journal-title":"Epidemiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1001\/archpedi.154.12.1226","article-title":"Prevalence and impact of dysmenorrhea on Hispanic female adolescents","volume":"154","author":"Banikarim","year":"2000","journal-title":"Arch. Pediatrics Adolesc. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2458-6-177","article-title":"WHO systematic review of prevalence of chronic pelvic pain: A neglected reproductive health morbidity","volume":"6","author":"Latthe","year":"2006","journal-title":"BMC Public Health"},{"key":"ref_4","first-page":"383","article-title":"Dysmenorrhea in adolescents and young adults: Prevalence, related factors and limitations in daily living","volume":"24","author":"Rodrigues","year":"2011","journal-title":"Acta Med. Port."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1111\/j.1471-0528.1996.tb09597.x","article-title":"A longitudinal study of risk factors for the occurrence, duration and severity of menstrual cramps in a cohort of college women","volume":"103","author":"Harlow","year":"1996","journal-title":"Bjog Int. J. Obstet. Gynaecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/j.1471-0528.1990.tb02545.x","article-title":"Factors influencing the prevalence and severity of dysmenorrhoea in young women","volume":"97","author":"Sundell","year":"1990","journal-title":"Bjog Int. J. Obstet. Gynaecol."},{"key":"ref_7","first-page":"98","article-title":"Risk factors for dysmenorrhea among young adult female university students","volume":"52","year":"2016","journal-title":"Ann. Ist. Super. Sanita"},{"key":"ref_8","first-page":"493","article-title":"Factors associated with dysmenorrhea among workers in French poultry slaughterhouses and canneries","volume":"35","author":"Messing","year":"1993","journal-title":"J. Occup. Med. Off. Publ. Ind. Med Assoc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e16307","DOI":"10.5812\/ircmj.16307","article-title":"Association of psychologic and nonpsychologic factors with primary dysmenorrhea","volume":"16","author":"Faramarzi","year":"2014","journal-title":"Iran. Red Crescent Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.jmwh.2004.08.013","article-title":"Primary dysmenorrhea: Assessment and management update","volume":"49","author":"Durain","year":"2004","journal-title":"J. Midwifery Womens Health"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rodriguez, M.B., Lethaby, A., and Farquhar, C. (2019). Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst. Rev., 9.","DOI":"10.1002\/14651858.CD000400.pub4"},{"key":"ref_12","first-page":"126","article-title":"Research and application of adlay in medicinal field","volume":"9","author":"Yu","year":"2017","journal-title":"Chin. Herb. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5103","DOI":"10.1021\/jf400556s","article-title":"Phytochemical profiles and antioxidant activity of adlay varieties","volume":"61","author":"Wang","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8886","DOI":"10.3390\/molecules17088886","article-title":"Protective effect of polyphenols extract of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) on hypercholesterolemia-induced oxidative stress in rats","volume":"17","author":"Wang","year":"2012","journal-title":"Molecules"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lin, P.-H., Shih, C.-K., Yen, Y.-T., Chiang, W., and Hsia, S.-M. (2019). Adlay (coix lachryma-jobi l. Var. Ma-yuen stapf.) hull extract and active compounds inhibit proliferation of primary human leiomyoma cells and protect against sexual hormone-induced mice smooth muscle hyperproliferation. Molecules, 24.","DOI":"10.3390\/molecules24081556"},{"key":"ref_16","first-page":"22","article-title":"Quercetin: A versatile flavonoid","volume":"2","author":"Lakhanpal","year":"2007","journal-title":"Internet J. Med Update"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1002\/ptr.3678","article-title":"Antiproliferative activity of flavonoids: Influence of the sequential methoxylation state of the flavonoid structure","volume":"26","author":"Moghaddam","year":"2012","journal-title":"Phytother. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1002\/jcp.25026","article-title":"Anti proliferative and pro apoptotic effects of flavonoid quercetin are mediated by CB1 receptor in human colon cancer cell lines","volume":"230","author":"Refolo","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4103\/0973-7847.194044","article-title":"Overviews of biological importance of quercetin: A bioactive flavonoid","volume":"10","author":"David","year":"2016","journal-title":"Pharmacogn. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.jff.2015.09.028","article-title":"Quercetin, a main flavonoid in onion, inhibits the PGF2\u03b1-induced uterine contraction in vitro and in vivo","volume":"19","author":"Wu","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/sj.bjp.0706951","article-title":"(+\/\u2212)-Naringenin as large conductance Ca2+-activated K+ (BKCa) channel opener in vascular smooth muscle cells","volume":"149","author":"Saponara","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"E719","DOI":"10.1152\/ajpendo.90367.2008","article-title":"Effects of adlay hull extracts on uterine contraction and Ca2+ mobilization in the rat","volume":"295","author":"Hsia","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/jsfa.4219","article-title":"Effects of adlay bran and its ethanolic extract and residue on preneoplastic lesions of the colon in rats","volume":"91","author":"Li","year":"2011","journal-title":"J. Sci. Food Agric."},{"key":"ref_24","first-page":"233","article-title":"The establishment of the dysmenorrhea model in mice","volume":"18","author":"Sun","year":"2002","journal-title":"Chin. Pharmacol. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0160-5402(80)90017-0","article-title":"A method for evaluating analgesic agents in rats","volume":"4","author":"Fukawa","year":"1980","journal-title":"J. Pharmacol. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0014-2999(99)00790-6","article-title":"Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice","volume":"387","author":"Ribeiro","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","first-page":"207","article-title":"Menstrual pain: Its origin and pathogenesis","volume":"25","author":"Rosenwaks","year":"1980","journal-title":"J. Reprod. Med."},{"key":"ref_28","unstructured":"Noble, D. (2012). The effects of prostaglandin F2\u03b1 on the force\/calcium relationship in pregnant rat myometrium. [Ph.D. Thesis, University of Liverpool]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/pm\/pnw121","article-title":"Effects of calcium-Vitamin D and calcium-alone on pain intensity and menstrual blood loss in women with primary dysmenorrhea: A randomized controlled trial","volume":"18","author":"Zarei","year":"2017","journal-title":"Pain Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/B978-0-12-374145-5.00127-3","article-title":"Calcium signaling in smooth muscle","volume":"3","author":"Wray","year":"2010","journal-title":"Handb. Cell Signal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/sj.bjp.0703190","article-title":"Distinct Ca2+ signalling mechanisms induced by ATP and sphingosylphosphorylcholine in porcine aortic smooth muscle cells","volume":"129","author":"Chin","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0028-2243(94)90154-6","article-title":"Some mechanical properties of skinned fibres of pregnant human myometrium","volume":"56","author":"Izumi","year":"1994","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_33","unstructured":"Liu, C.X., Pei-Gen, X., and Da-peng, L. (2000). Modern Research and Application of Chinese Medicinal Plants, Hong Kong Medical Publishers."},{"key":"ref_34","unstructured":"L\u00f3pez, L.M.B., Landoni, M.F., and Mart\u00edn-Jim\u00e9nez, T. (2002). Farmacolog\u00eda y Terap\u00e9utica Veterinaria, McGraw Hill Interamericana."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s11255-016-1248-5","article-title":"Urological complications of uterine leiomyoma: A review of literature","volume":"48","author":"Dagur","year":"2016","journal-title":"Int. Urol. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1016\/S0968-0896(03)00232-3","article-title":"Effect of O-glycosilation on the antioxidant activity and free radical reactions of a plant flavonoid, chrysoeriol","volume":"11","author":"Mishra","year":"2003","journal-title":"Bioorganic Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s00394-006-0620-0","article-title":"Selective bronchodilatory effect of Rooibos tea (Aspalathus linearis) and its flavonoid, chrysoeriol","volume":"45","author":"Khan","year":"2006","journal-title":"Eur. J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"T\u00f3th, B., Bartho, L., Vasas, A., S\u00e1ndor, Z., Jedlinszki, N., Pinke, G., and Hohmann, J. (2015). Dual excitatory and smooth muscle-relaxing effect of Sideritis montana extract on guinea-pig ileum. Nat. Prod. Commun., 10.","DOI":"10.1177\/1934578X1501000327"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jep.2018.05.024","article-title":"Extracts of compound Muniziqi granule suppressed uterus contraction and ameliorated oxytocin-induced primary dysmenorrhea","volume":"223","author":"Wei","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jep.2017.05.023","article-title":"The essential oil from the twigs of Cinnamomum cassia Presl inhibits oxytocin-induced uterine contraction in vitro and in vivo","volume":"206","author":"Sun","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"348","DOI":"10.4103\/0976-500X.103699","article-title":"Acetic acid induced painful endogenous infliction in writhing test on mice","volume":"3","author":"Gawade","year":"2012","journal-title":"J. Pharmacol. Pharmacother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/newbio236141a0","article-title":"Nociceptive response to prostaglandins and analgesic actions of aspirin and morphine","volume":"236","author":"Collier","year":"1972","journal-title":"Nat. New Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00520-018-4313-z","article-title":"The effect of a coix seed oil injection on cancer pain relief","volume":"27","author":"Zhang","year":"2019","journal-title":"Supportive Care Cancer"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/6\/887\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:16:13Z","timestamp":1760163373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/6\/887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,15]]},"references-count":43,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["biom11060887"],"URL":"https:\/\/doi.org\/10.3390\/biom11060887","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,15]]}}}