Toxicity Assessment of Nine Types of Decoction Pieces from the Daughter Root of Aconitum carmichaeli (Fuzi) Based on the Chemical Analysis of their Diester Diterpenoid Alkaloids

Abstract

Various processed types of Fuzi (the daughter roots of the highly toxic plant Aconitum carmichaeli Debx, FZ) decoction pieces (the herbal materials processed according to the specifications of Chinese medicine manuals; “Yinpian” in Chinese transliteration) are widely used in traditional medicine to treat various diseases, but their toxicities are not known. Nine types of FZ decoction pieces, including one raw slice and eight processed forms, were therefore prepared, each in 7 to 10 batches, to assess for their toxicity. Altogether 84 FZ samples were quantified on the amount of highly toxic diester diterpenoid alkaloids, i.e., aconitine, mesaconitine and hypaconitine by a newly developed HPLC method with HPLC‐DAD and LC‐MS techniques. The comparison of the processed FZ to raw slices of the root showed that the amount of each analyte in the processed FZ was drastically decreased. The sum of the three toxic compounds in the 8 types of processed FZ was only 3.91–34.80 % of this value in the FZ raw slice. This implies that the toxicity of processed FZ was decreased significantly. The amounts of toxic components in the 8 types of processed FZ varied significantly, often by a power of ten, indicating that the dosage of these herbs, when prescribed for clinical uses, should be cautiously set in order to avoid poisoning incidents.

Key words

Aconitum carmichaeli Debx - Ranunculaceae - daughter root - diester diterpenoid alkaloids - toxicity

References

• 1 Ameri A. The effects of Aconitum alkaloids on the central nervous system.  Prog Neurobiol. 1998;  56 211-235
• 2 Mizugaki M, Ito K. Aconite toxins. Suzuki O, Watanabe K Drugs and poisons in humans – a handbook of practical analysis. New York; Springer Verlag 2005: 456-467
• 3 The Compile Commission of Zhonghua Bencao of the State Administration of Traditional Chinese Medicine of the People“s Republic of China .Zhonghua Bencao, part 5. Shanghai; Shanghai Science and Technology Press 1999: 101-120
• 4 Xiao P G. New Chinese Materia Medica (Xin Bian Zhong Yao Zhi), Vol. 1. Beijing; Chemical Industry Press 2002 536-441 645-660
• 5 Zou J M, Wang L S. Superficial analysis of Chinese materia medica processing status.  Chin Tradit Herbal Drugs. 2005;  36 620-623
• 6 Tai Y T, But P P H, Young K, Lan C P. Cardiotoxicity after accidental herb-induced aconite poisoning.  Lancet. 1992;  340 1254-1256
• 7 Chan T Y K, Tomlinson B, Critchley J A J H. Aconitine poisoning following the ingestion of Chinese herbal medicines: report of eight cases.  Aust NZ J Med. 1993;  23 267-271
• 8 Chan T Y K, Tomlinson B, Chan W W M, Yeung V T F, Tse L K K. A case of acute aconitine poisoning caused by Chuanwu and Caowu.  J Trop Med Hyg. 1993;  96 62-63
• 9 Nagasaka K. Aconitine poisoning – determining the cause.  J Tradit Med. 2001;  18 141-146
• 10 Yoshioka N, Gonmori K, Tagashira A, Boonhooi O, Hayashi M, Saito Y, Mizugaki M. A case of aconitine poisoning with analysis of aconitine alkaloids by GC/SIM.  Forensic Sci Int. 2006;  81 117-123
• 11 Beike J, Frommherz M, Wood M, Brinkmann B, Köhler H. Determination of aconitine in body fluids by LC-MS-MS.  Int J Legal Med. 2004;  118 289-293
• 12 Pharmacopoeia of China, part 1. Beijing; Chemical Industry Press 2005 26-27 132-133 163-164
• 13 Huang Q A, Zhang Y M, He Y, Lu J, Lin R C. Studies on hydrolysis of aconitine.  Chin J Chin Mater Med. 2007;  32 2143-2145
• 14 Wang X T. Li Dai Zhongyao Paozhi Fa Huidian (ancient part). Nanchang; Jiangxi Science and Technology Press 1998: 97-102
• 15 Lu X Q. Zhongyao Paozhi Daquan. Changsha; Hunan Science and Technology Press 1999: 271-274
• 16 Jiao S D. Ten Lectures on the use of medicinals. New Nexico; Paradigm Publications 2003: 339-343
• 17 Liu X X, Chao R B. Determination of alkaloids in Radix Aconiti Lateralis Preparata by RP-ion-pair HPLC.  Acta Pharm Sin. 2006;  41 365-369
• 18 Zhang Y M, Liu J, Jiang Y, Yang K, Li Y R, Cheng X L. HPLC determination of Aconitum alkaloids and their hydrolysis products in Radix Aconiti and its preparata.  Chin J Pharm Anal. 2005;  25 807-812
• 19 Xie Y, Jiang Z H, Zhou H, Xu H X, Liu L. Simultaneous determination of six Aconitum alkaloids in proprietary Chinese medicines by high-performance liquid chromatography.  J Chromatogr A. 2005;  1093 195-203
• 20 Wang Z, Wen J, Xing J, He Y. Quantitative determination of diterpenoid alkaloids in four species of Aconitum by HPLC.  J Pharm Biomed Anal. 2006;  40 1031-1034
• 21 Wada K, Bando H, Kawahara N. Determination and quantitative analysis of Aconitum alkaloids in plants by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.  J Chromatogr. 1993;  644 43-48
• 22 Wada K, Bando H, Kawahara N, Mori T, Murayama M. Determination andquantitative analysis of alkaloids in Aconitum japonicum by liquid chromatography atmospheric pressure chemical ionization mass spectrometry.  Biol Mass Spectrom. 1994;  23 97-102
• 23 Ito K, Ohyama Y, Hishinuma T, Mizugaki M. Determination of Aconitum alkaloids in the tubers of Aconitum japonicum using gas chromatography/selected ion monitoring.  Planta Med. 1996;  62 57-59
• 24 Qi S, Cui S, Cheng Y, Chen X, Hu Z. Rapid separation and determination of aconitine alkaloids in traditional Chinese herbs by capillary electrophoresis using 1-butyl-3-methylimidazoium-based ionic liquid as running electrolyte.  Biomed Chromatogr. 2006;  20 294-300
• 25 Sun A, Chen D, Bi P. Determination of the aconitine alkaloids in traditional Chinese medicine Chuanwu and Caowu by high performance capillary electrophoresis (HPCE).  Chin J Chromatogr. 1999;  17 67-69
• 26 Liu Y, Liu S, Pei Q, Zhou Y, Yang D. Simultaneous content determination of aconitine, hypaconitine and mesaconitine in Fuzi by HPLC.  China Pharm. 2006;  17 1255-1256
• 27 Wang Y, Liu Z, Song F, Liu S. Electrospray ionization tandem mass spectrometric study of the aconitines in the roots of aconite.  Rapid Commun Mass Spectrom. 2002;  16 2075-2082
• 28 Ye D J, Zhang S C. Zhongyao Paozhi Xue. Beijing; People's Health Press 1999: 322-326
• 29 Bello-Ramírez A M, Buendía-Orozco J, Nava-Ocampo A A. A QSAS analysis to explain the analgesic properties of Aconitum alkaloids.  Fundam Clin Pharmacol. 2003;  17 575-580
• 30 Bello-Ramírez A M, Nava-Ocampo A A. The local anesthetic activity of Aconitum alkaloids can be explained by structural properties: a QSAR analysis.  Fundam Clin Pharmacol. 2004;  18 157-161
• 31 Dong L F, Liu J S, Song S X, Wang H M, Lu Z J. Cooperative effects of monkshood polysaccharide with adriamycin magnetic albumin microsphere targeting therapy on tumor.  J China Pharm Univ. 2003;  34 549-553
• 32 Zhao C, Li M, Luo Y, Wu W. Isolation and structural characterization of an immunostimulating polysaccharide from fuzi, Aconitum carmichaeli.  Carbohydr Res. 2006;  341 485-491