{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:38:33Z","timestamp":1791920313327,"version":"4.3.4"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1016\/j.jep.2022.115827","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T04:24:43Z","timestamp":1665462283000},"page":"115827","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Overlooked switch from transient sedation to sustained excitement in the Biphasic effects of Ephedra Herb extract administered orally to mice"],"prefix":"10.1016","volume":"301","author":[{"given":"Xuedan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7612-2870","authenticated-orcid":false,"given":"Sumiko","family":"Hyuga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Amakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0467-083X","authenticated-orcid":false,"given":"Masashi","family":"Hyuga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahoko","family":"Uchiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Hakamatsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5617-3670","authenticated-orcid":false,"given":"Yukihiro","family":"Goda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8863-1557","authenticated-orcid":false,"given":"Hiroshi","family":"Odaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Hanawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4289-7392","authenticated-orcid":false,"given":"Yoshinori","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jep.2022.115827_bib1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1254\/fpj.79.401","article-title":"Effect of d-pseudoephedrine on the central nervous system in mice","volume":"79","author":"Akiba","year":"1982","journal-title":"Folia Pharmacol. Jpn."},{"key":"10.1016\/j.jep.2022.115827_bib2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2344\/0003-3006-59.4.159","article-title":"Basic and clinical pharmacology of autonomic drugs","volume":"59","author":"Becker","year":"2012","journal-title":"Anesth. Prog."},{"key":"10.1016\/j.jep.2022.115827_bib3","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.jvs.2012.04.012","article-title":"Attenuation of spinal cord ischemia-reperfusion injury by specific alpha-2a receptor activation with dexmedetomidine","volume":"56","author":"Bell","year":"2012","journal-title":"J. Vasc. Surg."},{"key":"10.1016\/j.jep.2022.115827_bib4","first-page":"87","article-title":"The action of adrenoceptor agonists and antagonists on the Guinea pig and dog trachea","volume":"6","author":"Bilcikova","year":"1987","journal-title":"Gen. Physiol. Biophys."},{"key":"10.1016\/j.jep.2022.115827_bib5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.5582\/bst.2019.01244","article-title":"The toxicity and safety of traditional Chinese medicines: please treat with rationality","volume":"13","author":"Cai","year":"2019","journal-title":"Biosci Trends"},{"key":"10.1016\/j.jep.2022.115827_bib6","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1016\/j.neubiorev.2012.07.011","article-title":"Alpha 2 adrenergic receptor dysregulation in depressive disorders: implications for the neurobiology of depression and antidepressant therapy","volume":"36","author":"Cottingham","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.jep.2022.115827_bib7","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.3389\/fphar.2018.01196","article-title":"Oral delivered dexmedetomidine promotes and consolidates non-rapid eye movement sleep via sleep-wake regulation systems in mice","volume":"9","author":"Feng","year":"2018","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jep.2022.115827_bib8","doi-asserted-by":"crossref","first-page":"9563","DOI":"10.1039\/D1FO02093E","article-title":"Over a century since ephedrine discovery: an updated revisit to its pharmacological aspects, functionality, and toxicity in comparison to its herbal extracts","volume":"12","author":"Gad","year":"2021","journal-title":"Food Funct."},{"key":"10.1016\/j.jep.2022.115827_bib9","doi-asserted-by":"crossref","first-page":"5146","DOI":"10.3390\/ijms22105146","article-title":"Pseudoephedrine-Benefits and risks","volume":"22","author":"G\u0142owacka","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jep.2022.115827_bib10","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.neuint.2009.05.014","article-title":"alpha(2)-Adrenoceptor subtypes-mediated physiological, pharmacological actions","volume":"55","author":"Gyires","year":"2009","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.jep.2022.115827_bib11","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1248\/cpb.28.2900","article-title":"Antiinflammatory principle of ephedra herbs","volume":"28","author":"Hikino","year":"1980","journal-title":"Chem. Pharm. Bull. (Tokyo)"},{"key":"10.1016\/j.jep.2022.115827_bib12","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s11418-016-0979-z","article-title":"Ephedrine alkaloids-free Ephedra Herb extract: a safer alternative to ephedra with comparable analgesic, anticancer, and anti-influenza activities","volume":"70","author":"Hyuga","year":"2016","journal-title":"J. Nat. Med."},{"key":"10.1016\/j.jep.2022.115827_bib13","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1540\/jsmr.32.155","article-title":"Effects of optical isomers of ephedrine and methylephedrine on the twitch response in the isolated rat vas deferens and the involvement of alpha 2-adrenoceptors","volume":"32","author":"Kawasuji","year":"1996","journal-title":"J. Smooth Muscle Res."},{"key":"10.1016\/j.jep.2022.115827_bib14","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1248\/bpb.32.1235","article-title":"Molecular analysis and chemical evaluation of ephedra plants in Mongolia","volume":"32","author":"Kitani","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.jep.2022.115827_bib15","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.neuint.2007.06.036","article-title":"Alpha 2-adrenoceptor subtypes--unexpected functions for receptors and ligands derived from gene-targeted mouse models","volume":"51","author":"Knaus","year":"2007","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.jep.2022.115827_bib16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.anorl.2014.11.001","article-title":"Benefits, limits and danger of ephedrine and pseudoephedrine as nasal decongestants","volume":"132","author":"Laccourreye","year":"2014","journal-title":"Eur Ann Otorhinolaryngol Head Neck Dis"},{"key":"10.1016\/j.jep.2022.115827_bib17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1017\/S1073110500007506","article-title":"FDA to ban sales of dietary supplements containing ephedra","volume":"32","author":"Ling","year":"2004","journal-title":"J. Law Med. Ethics"},{"key":"10.1016\/j.jep.2022.115827_bib18","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1600-0773.1978.tb02282.x","article-title":"Pharmacokinetics and locomotor activity increasing effect of ephedrine in mice","volume":"43","author":"Marvola","year":"1978","journal-title":"Acta Pharmacol. Toxicol."},{"key":"10.1016\/j.jep.2022.115827_bib19","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.pbb.2005.03.008","article-title":"Mecamylamine attenuates ephedrine-induced hyperactivity in rats","volume":"81","author":"Miller","year":"2005","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.jep.2022.115827_bib20","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1248\/bpb.b19-00260","article-title":"Analgesic effects of ephedra herb extract, ephedrine alkaloids-free ephedra herb extract, ephedrine, and pseudoephedrine on formalin-induced pain","volume":"42","author":"Nakamori","year":"2019","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.jep.2022.115827_bib21","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/bjp.2008.341","article-title":"Dexmedetomidine and ST-91 analgesia in the formalin model is mediated by alpha2A-adrenoceptors: a mechanism of action distinct from morphine","volume":"155","author":"Nazarian","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jep.2022.115827_bib22","first-page":"22","article-title":"The first materia medica: the shen nong ben cao jing","author":"Nugent-Head","year":"2014","journal-title":"J. Chin. Med."},{"key":"10.1016\/j.jep.2022.115827_bib23","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1007\/s11418-016-0977-1","article-title":"Efficiently prepared ephedrine alkaloids-free Ephedra Herb extract: a putative marker and antiproliferative effects","volume":"70","author":"Oshima","year":"2016","journal-title":"J. Nat. Med."},{"key":"10.1016\/j.jep.2022.115827_bib24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00213-004-2048-7","article-title":"Forced swimming test in mice: a review of antidepressant activity","volume":"177","author":"Petit-Demouliere","year":"2005","journal-title":"Psychopharmacology (Berl)"},{"key":"10.1016\/j.jep.2022.115827_bib25","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1046\/j.1365-2885.1999.00231.x","article-title":"A pharmacokinetic study including some relevant clinical effect of medetomidine and atipamezole in lactating dairy cows","volume":"22","author":"Ranheim","year":"1999","journal-title":"J. Vet. Pharmacol. Therapeut."},{"key":"10.1016\/j.jep.2022.115827_bib26","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1124\/jpet.103.053975","article-title":"In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates","volume":"307","author":"Rothman","year":"2003","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.jep.2022.115827_bib27","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1055\/s-0030-1250533","article-title":"Toxicological risks of Chinese herbs","volume":"76","author":"Shaw","year":"2010","journal-title":"Planta Med."},{"key":"10.1016\/j.jep.2022.115827_bib28","series-title":"Ephedrine. StatPearls","first-page":"11","author":"Statler","year":"2022"},{"key":"10.1016\/j.jep.2022.115827_bib29","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1002\/ptr.6649","article-title":"p \u2010Synephrine, ephedrine, p \u2010octopamine and m \u2010synephrine: comparative mechanistic, physiological and pharmacological properties","volume":"34","author":"Stohs","year":"2020","journal-title":"Phytother Res."},{"key":"10.1016\/j.jep.2022.115827_bib30","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1055\/s-0035-1545725","article-title":"Inhalation administration of the sesquiterpenoid aristolen-1(10)-en-9-ol from Nardostachys chinensis has a sedative effect via the GABAergic system","volume":"81","author":"Takemoto","year":"2015","journal-title":"Planta Med."},{"key":"10.1016\/j.jep.2022.115827_bib31","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1248\/bpb.b14-00136","article-title":"Inhalation administration of valerena-4,7(11)-diene from Nardostachys chinensis roots ameliorates restraint stress-induced changes in murine behavior and stress-related factors","volume":"37","author":"Takemoto","year":"2014","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.jep.2022.115827_bib32","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1248\/bpb.b17-00803","article-title":"Ephedrine alkaloids-free ephedra herb extract, EFE, has No adverse effects such as excitation, insomnia, and arrhythmias","volume":"41","author":"Takemoto","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.jep.2022.115827_bib33","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0031-6997(25)07025-5","article-title":"Supersensitivity and subsensitivity to sympathomimetic amines","volume":"15","author":"Trendelenburg","year":"1963","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.jep.2022.115827_bib34","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S0006-2952(99)00152-5","article-title":"Direct effects of ephedrine isomers on human beta-adrenergic receptor subtypes","volume":"58","author":"Vansal","year":"1999","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.jep.2022.115827_bib35","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/0306-3623(93)90229-Q","article-title":"The effect of ephedrine isomers and their oxazolidines on locomotor activity in rats","volume":"24","author":"Walker","year":"1993","journal-title":"Gen. Pharmacol."},{"key":"10.1016\/j.jep.2022.115827_bib36","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1007\/s00210-019-01786-0","article-title":"Pharmacokinetics of seven major active components of Mahuang decoction in rat blood and brain by LC-MS\/MS coupled to microdialysis sampling","volume":"393","author":"Wan","year":"2020","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"10.1016\/j.jep.2022.115827_bib37","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jep.2009.07.040","article-title":"Quality and safety of Chinese herbal medicines guided by a systems biology perspective","volume":"126","author":"Wang","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2022.115827_bib38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s002130050494","article-title":"Effects of (-)-ephedrine on locomotion, feeding, and nucleus accumbens dopamine in rats","volume":"135","author":"Wellman","year":"1998","journal-title":"Psychopharmacology (Berl)"},{"key":"10.1016\/j.jep.2022.115827_bib39","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1248\/cpb.c19-00761","article-title":"Quality evaluation and characterization of fractions with biological activity from ephedra herb extract and ephedrine alkaloids-free ephedra herb extract","volume":"68","author":"Yoshimura","year":"2020","journal-title":"Chem. Pharm. Bull. (Tokyo)"}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874122008662?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874122008662?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:32:11Z","timestamp":1759944731000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874122008662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":39,"alternative-id":["S0378874122008662"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2022.115827","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Overlooked switch from transient sedation to sustained excitement in the Biphasic effects of Ephedra Herb extract administered orally to mice","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2022.115827","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"115827"}}