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      In vivo acute toxicity of detoxified Fuzi (lateral root of Aconitum carmichaeli) after a traditional detoxification process

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          Abstract

          Many herbs of traditional Chinese medicine (TCM) possess not only therapeutic efficacy, but also toxicity towards normal tissues. The herbal toxicities occasionally cause serious adverse events or even fatal poisoning due to the erroneous use of TCM herbs. Fuzi (lateral root of Aconitum carmichaeli) is such an herb with its toxic ingredient, aconites. Aconitine, mesaconitine, and hypaconitine are the main toxic components of Fuzi, which are hydrolyzed into non-toxic derivatives by water decoction. Therefore, long-time decoction was commonly applied as a traditional way to detoxify Fuzi before use. Nevertheless, recent clinical trials presorted on adverse events induced by long-time decocted Fuzi, putting some doubt on the safety of Fuzi after the traditional detoxification procedure. To thoroughly determine whether or not long-time decocted Fuzi was safe, we conducted in vivo acute toxicity assays using both rodent and zebrafish models and performed chemoprofile analyses using HPLC and UPLC-MS. The HPLC analysis showed that toxic aconitine components were hydrolyzed into benzoyl derivatives with increasing time of decoction. These aconitines were undetected by HPLC in Fuzi after 2 h-decoction (FZ-120), indicating seemingly non-toxicity of FZ-120. Unlike the non-decocted Fuzi (FZ-0) and 60 min-decocted Fuzi (FZ-60) with lethal toxicity, FZ-120 at 130 g/kg did not cause any deaths or side effects in mice regarding body weight and biochemical parameters. This seems to confirm safety of Fuzi after long-time decoction. However, histopathological observations revealed an abnormal liver phenotype and a significant decrease of the liver index following FZ-120 treatment, indicating a potential hepatoxicity of FZ-120. By using a zebrafish model, we observed that FZ-120 at a dose range from 288 to 896 μg/ml caused considerable adverse events including arrhythmia, liver degeneration, yolk sac absorption delay, length decrease, and swim bladder loss, which clearly speak for acute toxicity on cardiovascular, digestive, development, and respiratory systems. The dose range of FZ-120 was lower than that used for clinical application in human beings. Moreover, UPLC-MS revealed that FZ-120 still contained toxic aconitines that were not detectable by HPLC, which might explain its acute toxicity in zebrafish. We concluded that Fuzi is not sufficiently safe even after long-time decoction. The zebrafish model combined with UPLC-MS assay may represent an appropriate test system to unravel aconitine-related acute toxicity.

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          Drug-induced hepatotoxicity.

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            Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus.

            The rapidly increasing diabetes mellitus is becoming a serious threat to mankind health in all parts of the world. The control and treatment of diabetes and its complications mainly depend on the chemical or biochemical agents, but the fact is that it has never been reported that someone had recovered totally from diabetes. With the distinctive traditional medical opinions and natural medicines mainly originated in herbs, the traditional Chinese medicine performed a good clinical practice and is showing a bright future in the therapy of diabetes mellitus and its complications. Based on a large number of chemical and pharmacological research work, numerous bioactive compounds have been found in Chinese medicinal plants for diabetes. The present paper reviews 86 natural medicines with regards to their origin, anti-diabetic active principles and/or pharmacological test results, which are commonly used in the traditional Chinese medical system and have demonstrated experimental or/and clinical anti-diabetic effectiveness. Among these natural medicines, 82 originate from plants and 4 from animals or insects, which covers 45 families. It is strongly significant to pay close attention to traditional Chinese medical therapeutics and natural medicines for treatment of diabetes mellitus and its complications. Copyright 2004 Elsevier Ireland Ltd.
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              Asian medicine. The new face of traditional Chinese medicine.

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                Author and article information

                Journal
                EXCLI J
                EXCLI J
                EXCLI J
                EXCLI Journal
                Leibniz Research Centre for Working Environment and Human Factors
                1611-2156
                31 August 2018
                2018
                : 17
                : 889-899
                Affiliations
                [1 ]The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
                [2 ]College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China
                [3 ]Changzheng Hospital, Second Military Medical University, Shanghai, China
                [4 ]Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
                [5 ]Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
                Author notes
                *To whom correspondence should be addressed: Jiawei Huang, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China, E-mail: hjw3657@ 123456163.com
                Article
                2018-1607 Doc889
                10.17179/excli2018-1607
                6295630
                30564068
                7dda4425-75c2-4d8b-91ea-382e418b0a96
                Copyright © 2018 Sun et al.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence ( http://creativecommons.org/licenses/by/4.0/) You are free to copy, distribute and transmit the work, provided the original author and source are credited.

                History
                : 08 August 2018
                : 24 August 2018
                Categories
                Original Article

                acute toxicity,aconitum carmichaeli,aconitine,zebrafish,uplc-ms

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