{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:37:41Z","timestamp":1778675861483,"version":"3.51.4"},"reference-count":13,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,8,5]],"date-time":"2018-08-05T00:00:00Z","timestamp":1533427200000},"content-version":"vor","delay-in-days":216,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007416","name":"Japan Health Sciences Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>Ephedra Herb is an important crude drug; it is used in various Traditional Japanese Medicine (Kampo) formulations. Its significant pharmacological effects have been believed to be attributed to ephedrine and pseudoephedrine, which sometimes induce adverse effects. On the other hand, it has been reported that some of these pharmacological effects are not dependent on ephedrine or pseudoephedrine. Ephedrine alkaloids\u2010free Ephedra Herb extract has been newly developed. It has been reported to have analgesic, anti\u2010influenza, and antimetastatic effects. This clinical trial was aimed at verifying the noninferiority of EFE\u2019s safety compared to that of Ephedra Herb extract (EHE) in humans. This was a single\u2010institution, double\u2010blinded, randomized, two\u2010drug, two\u2010stage, crossover comparative study. Twelve healthy male subjects were equally and randomly allocated into two groups: prior administration of EFE (EFE\u2010P) and prior administration of EHE (EHE\u2010P). In Stage 1, EFE and EHE were orally administered to the EFE\u2010P and EHE\u2010P groups, respectively, for six days. After a 4\u2010week washout period, Stage 2 was initiated wherein the subjects were given a study drug different from Stage 1 study drug for six days. Eleven adverse events with a causal relationship to the study drugs (EHE: 8; EFE: 3) were noted; all events were mild in severity. With regard to the incidence of adverse events, EHE and EFE administration, respectively, accounted for 4 cases (out of 12 subjects, similarly below) and 1 case of increased pulse rate (p=0.32) and 3 cases and 1 case of insomnia (p=0.59). Further, there was one case of hot flashes (p=1.00) due to EFE administration and one case of dysuria (p=1.00) due to EHE administration. There were no significant differences in the incidences of adverse events between EHE administration and EFE administration. Therefore, we concluded that EFE is not inferior to EHE in terms of safety.<\/jats:p>","DOI":"10.1155\/2018\/4625358","type":"journal-article","created":{"date-parts":[[2018,8,5]],"date-time":"2018-08-05T23:32:15Z","timestamp":1533511935000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Double\u2010Blind, Randomized, Crossover Comparative Study for Evaluating the Clinical Safety of Ephedrine Alkaloids\u2010Free Ephedra Herb Extract (EFE)"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8863-1557","authenticated-orcid":false,"given":"Hiroshi","family":"Odaguchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9030-9137","authenticated-orcid":false,"given":"Mariko","family":"Sekine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7612-2870","authenticated-orcid":false,"given":"Sumiko","family":"Hyuga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiko","family":"Hanawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1912-0718","authenticated-orcid":false,"given":"Keika","family":"Hoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinobu","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Aso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinwei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Hyuga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinori","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Hakamatsuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihiro","family":"Goda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Kumagai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,5]]},"reference":[{"key":"e_1_2_9_1_2","unstructured":"The Ministry of Health Labour and Welfare of Japan he Japanese Pharmacopoeia 17th edition Tokyo Japan 2016."},{"key":"e_1_2_9_2_2","first-page":"34","article-title":"Pharmacological studies on Ephedra","volume":"1","author":"Harada M.","year":"1980","journal-title":"The Journal of Traditional Sino-Japanese Medicine"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.28.2900"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-969503"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1073110500007506"},{"key":"e_1_2_9_6_2","unstructured":"HanawaT. 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Kokai Tokkyo Koho P 5786164 2015."},{"key":"e_1_2_9_7_2","first-page":"51","article-title":"Maoto, Kampo medicine, suppresses the metastatic potential of highly metastatic osteosarcoma cells","volume":"24","author":"Hyuga S.","year":"2007","journal-title":"Journal of Traditional Medicines"},{"key":"e_1_2_9_8_2","first-page":"128","article-title":"Ephedrae herba, a major component of maoto, inhibits the HGF-induced motility of human breast cancer MDA-MB-231 cells through suppression of c-met tyrosine phosphorylation and c-Met expression","volume":"28","author":"Hyuga S.","year":"2011","journal-title":"Journal of Traditional Medicines"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules18055326"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1350899"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-016-0977-1"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-016-0979-z"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b17-00803"}],"container-title":["Evidence-Based Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2018\/4625358.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2018\/4625358.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2018\/4625358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T04:58:53Z","timestamp":1722920333000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2018\/4625358"}},"subtitle":[],"editor":[{"given":"Takao","family":"Namiki","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":13,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1155\/2018\/4625358"],"URL":"https:\/\/doi.org\/10.1155\/2018\/4625358","archive":["Portico"],"relation":{},"ISSN":["1741-427X","1741-4288"],"issn-type":[{"value":"1741-427X","type":"print"},{"value":"1741-4288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]},"assertion":[{"value":"2018-05-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"4625358"}}