title: Efficiently prepared ephedrine alkaloids-free Ephedra Herb extract: a putative marker and antiproliferative effects.
abstract: Ephedrine alkaloids (EAs) have been considered the main pharmacologically active substances in Ephedra Herb (, Mao; EH) since they were first identified by Prof. N. Nagai, and are known to induce palpitation, hypertension, insomnia, and dysuria as side effects. Therefore, the administration of drugs containing EH to patients with cardiovascular-related diseases is severely contraindicated. While our previous studies suggest that some of the effects of EH may not be due to EAs, considering their side effects would be expedient to develop a new EAs-free EH extract (EFE). Here, we established a preparation method for EFE and revealed its chemical composition, including the content of herbacetin, a flavonoid aglycon present in EH and a potential putative marker for EFE quality control. In addition, we showed the antiproliferative effects of EFE against the H1975 non-small cell lung cancer (NSCLC) cell line. EFE was prepared from EH extract using the ion exchange resin SK-1B. LC/Orbitrap MS analysis revealed the removal of EAs, 6-methoxykynurenic acid, and 6-hydroxykynurenic acid from the original extract. Quantitative analysis of herbacetin using LC/MS in acid-hydrolyzed EFE showed that its content was 0.104 %. Although several alkaloidal constituents were removed from EH extract, the antiproliferative effect of EFE against H1975 cells was comparable to that of EH extract. These results indicate that EFE retained the anticancer effect of EH and demonstrated its potential for future development as a new herbal medicine with reduced side effects.
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.|Department of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1, Kitakanemaru, Ohtawara city, Tochigi, 324-8501, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Oshima
authors.affiliation: TOKIWA Phytochemical Co., Ltd., 158 Kinoko, Sakura-shi, Chiba, 285-0801, Japan.
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Clinical Research, Oriental Medicine Research Center of Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Hyuga
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Hyuga
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamakura
authors.affiliation: Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime, 790-8578, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hakamatsuka
authors.affiliation: Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime, 790-8578, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Amakura
authors.affiliation: Department of Clinical Research, Oriental Medicine Research Center of Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hanawa
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan. goda@nihs.go.jp.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Goda
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D029789:Ephedra / Q000737:chemistry*; D004809:Ephedrine / Q000032:analysis / Q000737:chemistry*; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D004809:Ephedrine
keywords: Antiproliferative effect; Chemical composition; Ephedra Herb; Ephedrine alkaloids-free Ephedra Herb extract; Herbacetin