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      Establishment of one-step approach to detoxification of hypertoxic aconite based on the evaluation of alkaloids contents and quality

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          Abstract

          Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.

          Most cited references23

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          A review on phytochemistry and pharmacological activities of the processed lateral root of Aconitum carmichaelii Debeaux.

          The processed lateral root of Aconitum carmichaelii Debeaux (Ranunculaceae), an extensively used traditional Chinese medicine, is known as Fuzi in China (Chinese: ), "bushi" in Japan, "Kyeong-Po Buja" in Korea, Chinese aconite, monkshood or Chinese wolfsbane. It has been used to treat shock resulting from acute myocardial infarction, low blood pressure, coronary heart disease, chronic heart failure, etc.
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            A review on phytochemistry, pharmacology and toxicology studies of Aconitum.

            A number of species belonging to herbal genus Aconitum are well-known and popular for their medicinal benefits in Indian, Vietnamese, Korean, Japanese, Tibetan and Chinese systems of medicine. It is a valuable drug as well as an unpredictable toxic material. It is therefore imperative to understand and control the toxic potential of herbs from this genus. In this review, the ethnomedicinal, phytochemistry, pharmacology, structure activity relationship and toxicology studies of Aconitum were presented to add to knowledge for their safe application. A total of about 76 of all aconite species growing in China and surrounding far-east and Asian countries are used for various medical purposes. The main ingredients of aconite species are alkaloids, flavonoids, free fatty acids and polysaccharides. The tuberous roots of genus Aconitum are commonly applied for various diseases such as rheumatic fever, painful joints and some endocrinal disorders. It stimulates the tip of sensory nerve fibres. These tubers of Aconitum are used in the herbal medicines only after processing. There remain high toxicological risks of the improper medicinal applications of Aconitum. The cardio and neurotoxicities of this herb are potentially lethal. Many analytical methods have been reported for quantitatively and qualitatively characterization of Aconitum. Aconitum is a plant of great importance both in traditional medicine in general and in TCM in particular. Much attention should be put on Aconitum because of its narrow therapeutic range. However, Aconitum's toxicity can be reduced using different techniques and then benefit from its pharmacological activities. New methods, approaches and techniques should be developed for chemical and toxicological analysis to improve its quality and safety. © 2014 Royal Pharmaceutical Society.
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              Quantitative and chemical fingerprint analysis for quality control of rhizoma Coptidischinensis based on UPLC-PAD combined with chemometrics methods.

              To control the quality of rhizoma Coptidis, a method based on ultra performance liquid chromatography with photodiode array detector (UPLC-PAD) was developed for quantitative analysis of five active alkaloids and chemical fingerprint analysis. In quantitative analysis, the five alkaloids showed good regression (R > 0.9992) within test ranges and the recovery of the method was in the range of 98.4-100.8%. The limit of detections and quantifications for five alkaloids in PAD were less than 0.07 and 0.22 microg/ml, respectively. In order to compare the UPLC fingerprints between rhizoma Coptidis from different origins, the chemometrics procedures, including similarity analysis (SA), hierarchical clustering analysis (HCA), principal component analysis (PCA) were applied to classify the rhizoma Coptidis samples according to their cultivated origins. Consistent results were obtained to show that rhizoma Coptidis samples could be successfully grouped in accordance with the province of origin. Furthermore, five marker constituents were screened out to be the main chemical marker, which could be applied to accurate discrimination and quality control for rhizoma Coptidis by quantitative analysis. This study revealed that UPLC-PAD method was simple, sensitive and reliable for quantitative and chemical fingerprint analysis, moreover, for the quality evaluation and control of rhizoma Coptidis.
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                Author and article information

                Journal
                CJNM
                Chinese Journal of Natural Medicines
                Elsevier
                1875-5364
                20 January 2017
                : 15
                : 1
                : 49-61
                Affiliations
                [1] 1Provincial and State Key Laboratory Breeding Base of System Research, Development and Utilization of Chinese Herbal Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
                [2] 2China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China
                [3] 3Key Laboratory of Modern Preparation of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
                [4] 4Integrative Medical Center, 302 Military Hospital, Beijing 100039, China
                [5] 5Sichuan Good Doctor Panxi Pharmaceutical Co., Ltd., Xichang 610031, China
                Author notes
                *Corresponding author: WANG Jia-Bo, E-mail: wjb0128@ 123456126.com ; YANG Ming, E-mail: yangming16@ 123456126.com

                These authors have no conflict of interest to declare.

                Article
                S1875-5364(17)30008-0
                10.1016/S1875-5364(17)30008-0
                28259253
                a1eb854f-2ab1-4dac-a186-ec1f920dc826
                Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
                History
                : 17 April 2015
                Funding
                Funded by: National Nature Science Fundation of China
                Award ID: 81274026
                Award ID: 81403115
                This work was supported by National Nature Science Fundation of China (Nos. 81274026 and 81403115).

                Medicine,Pharmaceutical chemistry,Pharmacology & Pharmaceutical medicine,Complementary & Alternative medicine
                Quantitative determination,Quality consistency,Cardiac effect,Detoxication methods,Aconite

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