title: Assessment of in vitro cardiotoxicity of extract fractions and diterpene alkaloids from Aconitum leucostomum Worosch: A short communication.
abstract: Aconitum leucostomum Worosch is a traditional Chinese medicine (TCM) and has a broad spectrum of health effects, but with a narrow therapeutic window. It is important to identify both the therapeutic ingredients and the toxic components to better utilize this TCM. The present study investigated the cardiotoxicity of the selected compounds in Aconitum leucostomum Worosch. The effects of extract of A. leucostomum Worosch and the isolated compounds on cardiocardiomyocytes were evaluated in vitro. Five known compounds in this TCM, including three C18-diterpene alkaloids, lappaconitine (2), N-deacetyllappaconitine (3), and ranaconitine (5), and two C19-diterpene alkaloids, delvestidine (1) and anthranoyllycoctonine (4), were isolated from A. leucostomum Worosch. The cardiotoxicity of these components and extract fractions, as measured by lactate dehydrogenase release and apoptosis, was ranked as follows, in descending order: delvestidine>anthranoyllycoctonine>pH 4 fraction>pH 8 fraction>aconitine>N-deacetyllappaconitine>ranaconitine>lappaconitine. The cytotoxicity of these compounds was shown to be dose-dependent, with delvestidine (1) and anthranoyllycoctonine (4) being the two most toxic compounds to cardiomyocytes in our assays. These results provide a basis for future rational use of this TCM, reducing side effects while retaining therapeutic effects.
authors.affiliation: Hospital of Traditional Chinese Medicine, Xinjiang Medical University, No. 116 Huanghe Road, Urumqi 830000, People's Republic of China. Electronic address: xjnjh411@163.com.
authors.forename: Jihong
authors.initials: J
authors.lastname: Nie
authors.affiliation: Hospital of Traditional Chinese Medicine, Xinjiang Medical University, No. 116 Huanghe Road, Urumqi 830000, People's Republic of China; Xinjiang Medical University, Urumqi 830000, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute of Materia Medica, Chinese Academy Medical Sciences and Peking Union Medical College, No.1 City Xicheng District Xiannongtan Jie, Beijing 100050, People's Republic of China. Electronic address: jitf@imm.ac.cn.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Ji
authors.affiliation: Department of Xinjiang Institute of Medicine, Urumqi 830000, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Hospital of Traditional Chinese Medicine, Xinjiang Medical University, No. 116 Huanghe Road, Urumqi 830000, People's Republic of China.
authors.forename: Feicui
authors.initials: F
authors.lastname: Zhao
mesh_terms: D000157:Aconitine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000737:chemistry; D031841:Aconitum / Q000009:adverse effects* / Q000737:chemistry*; D000470:Alkaloids / Q000009:adverse effects* / Q000737:chemistry; D000818:Animals; D066126:Cardiotoxicity / Q000209:etiology*; D002460:Cell Line; D004224:Diterpenes / Q000009:adverse effects* / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000009:adverse effects; D008516:Medicine, Chinese Traditional / Q000009:adverse effects; D051381:Rats
chemical_list: D000470:Alkaloids; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; C055260:N-deacetyllappaconitine; C079992:ranaconitine; D000157:Aconitine; C022150:lappaconitine
keywords: Aconitine; Aconitum leucostomum Worosch; Cardiomyocytes; Chemical composition; Toxicity