title: Distribution of toxic alkaloids in tissues from three herbal medicine Aconitum species using laser micro-dissection, UHPLC-QTOF MS and LC-MS/MS techniques.
abstract: Aconite poisoning continues to be a major type of poisoning caused by herbal drugs in many countries. Nevertheless, despite its toxic characteristics, aconite is used because of its valuable therapeutic benefits. The aim of the present study was to determine the distribution of toxic alkaloids in tissues of aconite roots through chemical profiling. Three species were studied, all being used in traditional Chinese Medicine (TCM) and traditional Indian medicine (Ayurveda), namely: Aconitum carmichaelii, Aconitum kusnezoffii and Aconitum heterophyllum. Laser micro-dissection was used for isolation of target microscopic tissues, such as the metaderm, cortex, xylem, pith, and phloem, with ultra-high performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS) employed for detection of metabolites. Using a multi-targeted approach through auto and targeted LC-MS/MS, 48 known compounds were identified and the presence of aconitine, mesaconitine and hypaconitine that are the biomarkers of this plant was confirmed in the tissues. These results suggest that the three selected toxic alkaloids were exclusively found in A. carmichaelii and A. kusnezoffii. The most toxic components were found in large A. carmichaelii roots with more lateral root projections, and specifically in the metaderm, cork and vascular bundle tissues. The results from metabolite profiling were correlated with morphological features to predict the tissue specific distribution of toxic components and toxicity differences among the selected species. By careful exclusion of tissues having toxic diester diterpenoid alkaloids, the beneficial effects of aconite can still be retained and the frequency of toxicity occurrences can be greatly reduced. Knowledge of tissue-specific metabolite distribution can guide users and herbal drug manufacturers in prudent selection of relatively safer and therapeutically more effective parts of the root. The information provided from this study can contribute towards improved and effective management of therapeutically important, nonetheless, toxic drug such as Aconite.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong Special Administrative Region, PR China.
authors.forename: Yogini
authors.initials: Y
authors.lastname: Jaiswal
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong Special Administrative Region, PR China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Liang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong Special Administrative Region, PR China.
authors.forename: Alan
authors.initials: A
authors.lastname: Ho
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong Special Administrative Region, PR China.
authors.forename: LaiLai
authors.initials: L
authors.lastname: Wong
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Haidian District, Beijing, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yong
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong Special Administrative Region, PR China.
authors.forename: Hubiao
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong Special Administrative Region, PR China. Electronic address: zzzhao@hkbu.edu.hk.
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification; D031841:Aconitum / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification*; D015394:Molecular Structure; D018517:Plant Roots / Q000737:chemistry
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; C058309:hypaconitine; C019470:mesaconitine; D000157:Aconitine
keywords: A. carmichaelii Debx.; A. kusnezoffii Reichb.; Aconitum heterophyllum Wall; Alkaloids; Ayurveda; Chemical profiling; LC–MS/MS; Laser micro-dissection; Ranunculaceae; Toxicity; Traditional Chinese medicine (TCM); UHPLC–QTOF MS