Clinical Aspects of Aconitum Preparations^[*]

Abstract

Aconite species have played an important role in human history. Aconitum species have been used worldwide as poisons as well as remedies. Their potential in targeting several ailments such as pain, rheumatism, and lethargy has been recognized by Western, Chinese, and Indian health care practitioners. Aconite use in herbal preparations has declined, especially in Europe and the United States, in the first half of the twentieth century due to several reported toxicity cases. The situation has changed with the application of new technologies for the accurate analysis of its toxic components and the development of efficient detoxification protocols. Some Asian countries started small clinical trials to evaluate the potency and safety of different marketed aconite preparations. The current review summarizes therapeutic uses of aconite preparations in China, Taiwan, India, and Japan. It also highlights clinical trial results with special emphasis on their limitations. Modern drugs and pharmacopoeial preparations derived from aconite are also discussed.

Key words

Aconitum - Ranunculaceae - fuzi - monkshood - traditional Chinese medicine - Ayurvedic medicine

^* Dedicated to Professor Dr. Dr. h. c. mult. Adolf Nahrstedt on the occasion of his 75th birthday.

^# These authors contributed equally to this work.

• References

• 1 Ding JY, Liu XX, Xiong DM, Ye LM, Chao RB. Simultaneous determination of thirteen aminoalcohol-diterpenoid alkaloids in the lateral roots of Aconitum carmichaeli by solid-phase extraction-liquid chromatography-tandem mass spectrometry. Planta Med 2014; 80: 723-731
• 2 Moog FP, Karenberg A. Toxicology in the old testament. Did the high priest acimus die of acute aconitine poisoning?. Adverse Drug React Toxicol Rev 2002; 21: 151-156
• 3 Nyirimigabo E, Xu Y, Li Y, Wang Y, Agyemang K, Zhang Y. A review on phytochemistry, pharmacology and toxicology studies of Aconitum . J Pharm Pharmacol 2015; 67: 1-19
• 4 Chan TY. Aconite poisoning. Clin Toxicol (Phila) 2009; 47: 279-285
• 5 Singhuber J, Zhu M, Prinz S, Kopp B. Aconitum in traditional Chinese medicine: a valuable drug or an unpredictable risk?. J Ethnopharmacol 2009; 126: 18-30
• 6 Gaillard Y, Pepin G. Poisoning by plant material: review of human cases and analytical determination of main toxins by high-performance liquid chromatography-(tandem) mass spectrometry. J Chromatogr B Biomed Sci Appl 1999; 733: 181-229
• 7 Sun WX, Song FR, Cui M, Liu SY. Simultaneous determination of lipo-alkaloids extracted from Aconitum carmiechaeli using electrospray ionization mass spectrometry and multiple tandem mass spectrometry. Planta Med 1999; 65: 432-436
• 8 Borcsa B, Csupor D, Forgo P, Widowitz U, Bauer R, Hohmann J. Aconitum lipo-alkaloids-semisynthetic products of the traditional medicine. Nat Prod Commun 2011; 6: 527-536
• 9 Plenert B, Prasa D, Hentschel H, Deters M. Plant exposures reported to the poisons information centre Erfurt from 2001–2010. Planta Med 2012; 78: 401-408
• 10 Bonnici K, Stanworth D, Simmonds MSJ, Mukherjee E, Ferner RE. Flowers of evil. Lancet 2010; 376: 1616
• 11 Qi Y, Li S, Pi Z, Song F, Lin N, Liu S, Liu Z. Chemical profiling of Wu-tou decoction by UPLC-Q-TOF-MS. Talanta 2014; 118: 21-29
• 12 Zheng Q, Zhao Y, Wang J, Liu T, Zhang B, Gong M, Li J, Liu H, Han B, Zhang Y, Song X, Li Y, Xiao X. Spectrum-effect relationships between UPLC fingerprints and bioactivities of crude secondary roots of Aconitum carmichaelii Debeaux (Fuzi) and its three processed products on mitochondrial growth coupled with canonical correlation analysis. J Ethnopharmacol 2014; 153: 615-623
• 13 Song JZ, Han QB, Qiao CF, But PP, Xu HX. Development and validation of a rapid capillary zone electrophoresis method for the determination of aconite alkaloids in aconite roots. Phytochem Anal 2010; 21: 137-143
• 14 Zhang J, Huang ZH, Qiu XH, Yang YM, Zhu da Y, Xu W. Neutral fragment filtering for rapid identification of new diester-diterpenoid alkaloids in roots of Aconitum carmichaeli by ultra-high-pressure liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry. PLoS One 2012; 7: e52352
• 15 Song L, Zhang H, Liu X, Zhao ZL, Chen SL, Wang ZT, Xu HX. Rapid determination of yunaconitine and related alkaloids in aconites and aconite-containing drugs by ultra high-performance liquid chromatography-tandem mass spectrometry. Biomed Chromatogr 2012; 26: 1567-1574
• 16 Zhang Q, Wang CH, Ma YM, Zhu EY, Wang ZT. UPLC-ESI/MS determination of 17 active constituents in two categorized formulas of traditional Chinese medicine, Sanhuang Xiexin Tang and Fuzi Xiexin Tang: application in comparing the differences in decoctions and macerations. Biomed Chromatogr 2013; 27: 1079-1088
• 17 Csupor D, Borcsa B, Heydel B, Hohmann J, Zupko I, Ma Y, Widowitz U, Bauer R. Comparison of a specific HPLC determination of toxic aconite alkaloids in processed radix aconiti with a titration method of total alkaloids. Pharm Biol 2011; 49: 1097-1101
• 18 Csupor D, Wenzig EM, Zupko I, Woelkart K, Hohmann J, Bauer R. Qualitative and quantitative analysis of aconitine-type and lipo-alkaloids of Aconitum carmichaelii roots. J Chromatogr A 2009; 1216: 2079-2086
• 19 Sun GB, Sun H, Meng XB, Hu J, Zhang Q, Liu B, Wang M, Xu HB, Sun XB. Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p 38 MAPK signaling pathway in rats. Toxicol Appl Pharmacol 2014; 279: 8-22
• 20 Li X, Jiang J, Shi S, Bligh SWA, Li Y, Jiang Y, Huang D, Ke Y, Wang S. A RG-II type polysaccharide purified from Aconitum coreanum alleviates lipopolysaccharide-induced inflammation by inhibiting the NF-κB signal pathway. PLoS One 2014; 9: e99697
• 21 Park KH, Park M, Choi SE, Jeong MS, Kwon JH, Oh MH, Choi HK, Seo SJ, Lee MW. The anti-oxidative and anti-inflammatory effects of caffeoyl derivatives from the roots of Aconitum koreanum R. Raymond. Biol Pharm Bull 2009; 32: 2029-2033
• 22 Shaw D. Toxicological risks of chinese herbs. Planta Med 2010; 76: 2012-2018
• 23 Lu G, Dong Z, Wang Q, Qian G, Huang W, Jiang Z, Leung KS, Zhao Z. 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. Planta Med 2010; 76: 825-830
• 24 Yang S. The divine farmerʼs materia medica: a translation of the Shen Nong Ben Cao Jing. Boulder: Blue Poppy Press; 1998
• 25 Xie H, Preast V, Beckford BJ. Xieʼs Chinese veterinary herbology. Singapore: Wiley; 2011
• 26 Zhang Z, Mitchell C, Feng Y, Wiseman N. Shang Han Lun: On cold damage, translation and commentaries. Brookline: Paradigm Publications; 1999
• 27 Zhao D, Wang J, Cui Y, Wu X. Pharmacological effects of Chinese herb aconite (Fuzi) on cardiovascular system. J Tradit Chin Med 2012; 32: 308-313
• 28 Liu C, Tseng A, Yang S. Chinese herbal medicine: modern applications of traditional formulas. Boca Raton: CRC Press; 2004
• 29 Yang Y. Chinese herbal formulas: Treatment principles and composition strategies. Beijing: Elsevier Health Sciences UK; 2010
• 30 Ross J. Combining Western herbs and Chinese medicine: Principles, practice, and materia medica. Hadley: Greenfields Press; 2003
• 31 Chen HC, Chen WC, Lin KH, Chen YH, Lo LC, Lee TC, Hsia TC, Wang CH, Wu SH, Hsu HW, Chang YJ, Huang YC, Ku TH, Horng MH. Simultaneous use of traditional Chinese medicine (si-ni-tang) to treat septic shock patients: study protocol for a randomized controlled trial. Trials 2011; 12: 199
• 32 Tao L, Shen S, Li X. Future prospects of Qiliqiangxin on heart failure: epigenetic regulation of regeneration. Front Genet 2013; 4: 221
• 33 Tao L, Shen S, Fu S, Fang H, Wang X, Das S, Sluijter JP, Rosenzweig A, Zhou Y, Kong X, Xiao J, Li X. Traditional Chinese Medication Qiliqiangxin attenuates cardiac remodeling after acute myocardial infarction in mice. Sci Rep 2015; 5: 8374
• 34 Li X, Zhang J, Huang J, Ma A, Yang J, Li W, Wu Z, Yao C, Zhang Y, Yao W, Zhang B, Gao R. A multicenter, randomized, double-blind, parallel-group, placebo-controlled study of the effects of qili qiangxin capsules in patients with chronic heart failure. J Am Coll Cardiol 2013; 62: 1065-1072
• 35 Xiao H, Song Y, Li Y, Liao YH, Chen J. Qiliqiangxin regulates the balance between tumor necrosis factor-alpha and interleukin-10 and improves cardiac function in rats with myocardial infarction. Cell Immunol 2009; 260: 51-55
• 36 Zou Y, Lin L, Ye Y, Wei J, Zhou N, Liang Y, Gong H, Li L, Wu J, Li Y, Jia Z, Wu Y, Zhou J, Ge J. Qiliqiangxin inhibits the development of cardiac hypertrophy, remodeling, and dysfunction during 4 weeks of pressure overload in mice. J Cardiovasc Pharmacol 2012; 59: 268-280
• 37 Liu W, Chen J, Xu T, Tian W, Li Y, Zhang Z, Li W. Qiliqiangxin improves cardiac function in spontaneously hypertensive rats through the inhibition of cardiac chymase. Am J Hypertens 2012; 25: 250-260
• 38 Zhang J, Wei C, Wang H, Tang S, Jia Z, Wang L, Xu D, Wu Y. Protective effect of qiliqiangxin capsule on energy metabolism and myocardial mitochondria in pressure overload heart failure rats. Evid Based Complement Alternat Med 2013; 2013: 378298
• 39 Wei Y, Liu X, Hou L, Che W, The E, Jhummon MV. Qiliqiangxin affects L type ca(2+) current in the normal and hypertrophied rat heart. Evid Based Complement Alternat Med 2012; 2012: 131830
• 40 Wei Y, Liu X, Wei H, Hou L, Che W, The E, Li G, Jhummon MV, Wei W. The electrophysiological effects of qiliqiangxin on cardiac ventricular myocytes of rats. Evid Based Complement Alternat Med 2013; 2013: 213976
• 41 Yang H, Liu L, Gao W, Liu K, Qi LW, Li P. Direct and comprehensive analysis of ginsenosides and diterpene alkaloids in Shenfu injection by combinatory liquid chromatography-mass spectrometric techniques. J Pharm Biomed Anal 2014; 92: 13-21
• 42 Wen-Ting S, Fa-Feng C, Li X, Cheng-Ren L, Jian-Xun L. Chinese medicine shenfu injection for heart failure: a systematic review and meta-analysis. Evid Based Complement Alternat Med 2012; 2012: 713149
• 43 Nilsson PM, Boutouyrie P, Cunha P, Kotsis V, Narkiewicz K, Parati G, Rietzschel E, Scuteri A, Laurent S. Early vascular ageing in translation: from laboratory investigations to clinical applications in cardiovascular prevention. J Hypertens 2013; 31: 1517-1526
• 44 Mo Y, Liu X, Qin X, Huang J, He Z, Lin J, Hu Q, Cai Y, Liu Z, Wang L. Shenfu injection for intradialytic hypotension: a systematic review and meta-analysis. Evid Based Complement Alternat Med 2014; 2014: 279853
• 45 Hu J, Fu Z, Xie Y, Wang J, Wang W, Liao X. [Systematic review of shenfu injection for septic shock]. Zhongguo Zhong Yao Za Zhi 2013; 38: 3209-3214
• 46 Gu Y, Xu H, Zhao M. [Clinical study on effect of Shenfu injection treating cancer-related fatigue of patients with advanced carcinoma]. Zhongguo Zhong Yao Za Zhi 2010; 35: 915-918
• 47 Wu WY, Long SQ, Zhang HB, Chai XS, Deng H, Xue XG, Wang B, Luo HY, Liu WS. Improvement of quality of life with Shenfu injection in non small cell lung cancer patients treated with gemcitabine plus cisplatin regimen. Chin J Integr Med 2006; 12: 50-54
• 48 Li YH, Yu B, Duan ZZ, Akinyi OM, Yu JH, Zhou K, Zhang Y, Gao XM. The coronary dilation effect of Shen Fu injection was mediated through NO. PLoS One 2014; 9: e92415
• 49 Zhang Y, Li CS, Wu CJ, Yang J, Hang CC. Neuroprotective effect of Shenfu Injection following cardiac arrest in pig correlates with improved mitochondrial function and cerebral glucose uptake. Chin J Integr Med 2014; 20: 835-843
• 50 Zhang Q, Li C. The roles of traditional chinese medicine: shen-fu injection on the postresuscitation care bundle. Evid Based Complement Alternat Med 2013; 2013: 319092
• 51 Huang L, Cao J. The protective effects of Shen-Fu injection on experimental acute pancreatitis in a rat model. Oxid Med Cell Longev 2014; 2014: 248786
• 52 Yang LJ, Wang J, Tian ZF, Yuan YF. Shenfu injection attenuates neonatal hypoxic-ischemic brain damage in rat. Neurol Sci 2013; 34: 1571-1574
• 53 Khare CP. Indian herbal remedies: Rational Western therapy, Ayurvedic, and other traditional usage. New York: Springer; 2003
• 54 Frawley D, Ranade S. Ayurveda, natureʼs medicine. Silver Lake: Lotus; 2001
• 55 Rastogi S. A review of Aconite (Vatsanabha) usage in Ayurvedic formulations: traditional views and their inferences. Spatula DD 2011; 1: 233-244
• 56 Valiathan S. The Legacy of Caraka. Hyderabad: Orient BlackSwan; 2003
• 57 Khare CP. Indian medicinal plants: An illustrated dictionary. Heidelberg: Springer; 2007
• 58 Khare CP, Katiyar CK. The modern Ayurveda: Milestones beyond the classical age. Boca Raton: Taylor & Francis; 2012
• 59 Chiu WT, Chang YS, Wu YC. Aconiti lateralis radix. Taiwan herbal pharmacopeia. 2nd. edition. Taipei: Committee on Chinese Medicine and Pharmacy Press; 2013
• 60 Wong SK. Determination of Aconitum alkaloids in dietary supplements and raw botanical materials by liquid chromatography/UV detection with confirmation by liquid chromatography/tandem mass spectrometry: collaborative study. J AOAC Int 2009; 92: 111-118
• 61 Yu F, Takahashi T, Moriya J, Kawaura K, Yamakawa J, Kusaka K, Itoh T, Morimoto S, Yamaguchi N, Kanda T. Traditional Chinese medicine and Kampo: a review from the distant past for the future. J Int Med Res 2006; 34: 231-239
• 62 Borchers AT, Sakai S, Henderson GL, Harkey MR, Keen CL, Stern JS, Terasawa K, Gershwin ME. Shosaiko-to and other Kampo (Japanese herbal) medicines: a review of their immunomodulatory activities. J Ethnopharmacol 2000; 73: 1-13
• 63 Hagino N. An overview of Kampo medicine: Toki-Shakuyaku-San (TJ-23). Phytother Res 1993; 7: 391-394
• 64 Yamada T. The tradition and genealogy of the Kampo medicine. Jpn J Orient Med 1996; 46: 505-518
• 65 Katayama K, Yoshino T, Munakata K, Yamaguchi R, Imoto S, Miyano S, Watanabe K. Prescription of kampo drugs in the Japanese health care insurance program. Evid Based Complement Alternat Med 2013; 2013: 576973
• 66 World Health Organization. Legal status of traditional medicine and complementary/alternative medicine: A worldwide review. Geneva: World Health Organization; 2001
• 67 Kakiuchi N, Atsumi T, Higuchi M, Kamikawa S, Miyako H, Wakita Y, Ohtsuka I, Hayashi S, Hishida A, Kawahara N. Diversity in aconitine alkaloid profile of Aconitum plants in Hokkaido contrasts with their genetic similarity. J Nat Med 2015; 69: 154-164
• 68 Society of Japanese Pharmacopoeia. The Japanese pharmacopoeia: JP XV: English version. Tokyo: Yakuji Nippo; 2006
• 69 Nakae H, Fujita Y, Igarashi T, Tajmi K, Endo S. Serum aconitine concentrations after taking powdered processed Aconiti tuber . Biomed Res 2008; 29: 225-231
• 70 Ono T, Hayashida M, Uekusa K, Lai CF, Hayakawa H, Nihira M, Ohno Y. An accidental case of aconite poisoning due to Kampo herbal medicine ingestion. Leg Med (Tokyo) 2009; 11: 132-135
• 71 Yamada K, Suzuki E, Nakaki T, Watanabe S, Kanba S. Aconiti tuber increases plasma nitrite and nitrate levels in humans. J Ethnopharmacol 2005; 96: 165-169
• 72 Nakanishi M, Arimitsu J, Kageyama M, Otsuka S, Inoue T, Nishida S, Yoshikawa H, Kishida Y. Efficacy of traditional Japanese herbal medicines-Keishikajutsubuto (TJ-18) and Bushi-matsu (TJ-3022)-against postherpetic neuralgia aggravated by self-reported cold stimulation: a case series. J Altern Complement Med 2012; 18: 686-692
• 73 Takizawa Y, Isono T, Suzuki Y, Hayakawa Y, Oyama T. [Analgesic effects of Tsumura-shuuji-bushi-matsu and mesaconitine]. Nihon Yakurigaku Zasshi 1992; 100: 307-316
• 74 Murayama M, Namiki Y. [Pharmacological study of kako-bushi-matsu: analgesic action and acute toxicity]. Nihon Yakurigaku Zasshi 1989; 94: 309-317
• 75 Abe Y. The efficacy of goshajinkigan against lymphedema. Kampo Igaku 2002; 25: 284-287
• 76 Okabe T, Tsutani K. Evidence reports of Kampo treatment 2010: 345 Randomized controlled trials (EKAT 2010). Tokyo: Jpn Soc Orient Med; 2010
• 77 Iwasaki K, Kobayashi S, Chimura Y, Taguchi M, Inoue K, Cho S, Akiba T, Arai H, Cyong JC, Sasaki H. A randomized, double-blind, placebo-controlled clinical trial of the Chinese herbal medicine “ba wei di huang wan” in the treatment of dementia. J Am Geriatr Soc 2004; 52: 1518-1521
• 78 Ernst E. A systematic review of systematic reviews of homeopathy. Br J Clin Pharmacol 2002; 54: 577-582
• 79 Haller jr. JS. Aconite: a case study in doctrinal conflict and the meaning of scientific medicine. Bull N Y Acad Med 1984; 60: 888-904
• 80 Piltan D, Rist L, Simoes-Wuest AP, Saller R. Test of a homeopathic dilution of Aconitum napellus a clinical, randomized, double-blind, controlled crossover study in healthy volunteers. Forsch Komplementarmed 2009; 16: 168-173
• 81 Friese K, Kruse S, Ludtke R, Moeller H. The homoeopathic treatment of otitis media in children-comparisons with conventional therapy. Int J Clin Pharmacol Ther 1997; 35: 296-301
• 82 Council of Europe. European pharmacopoeia. Strasbourg: Council of Europe; 2010
• 83 British Pharmacopoeia Commission. British pharmacopoeia 2009. London: TSO Publications; 2008
• 84 World Health Organization. The international pharmacopoeia. Geneva: World Health Organization; 2006
• 85 Sweetman SC. Martindale: The complete drug reference. London: Pharmaceutical Press; 2009
• 86 Troy DB, Remington JP, Beringer P. Remington: The science and practice of pharmacy. London: Lippincott Williams & Wilkins; 2006
• 87 Yunusov MS. Antiarrhythmic agents based on diterpenoid alkaloids. Russ Chem Bull 2011; 60: 633-638
• 88 Tolstikova TG, Tolstikov AG, Tolstikov GA. On the way to low-dose medicines. Her Russ Acad Sci 2007; 77: 447-453
• 89 Kurmukov A, Akimaliev A. A short history of medicinal plant use in central Asia. In: Eisenman SW, Zaurov DE, Struwe L, editors Medicinal plants of Central Asia: Uzbekistan and Kyrgyzstan. New York: Springer; 2013: 9-12
• 90 Dzhakhangirov FN, Sultankhodzhaev MN, Tashkhodzhaev B, Salimov BT. Diterpenoid alkaloids as a new class of antiarrhythmic agents. Structure-activity relationship. Chem Nat Compd 1997; 33: 190-202
• 91 Sadikov AZ, Shakirov TT. Preparation of allapinin from the epigeal part of Aconitum leucostomum . Khim Prir Soedin 1988; 91: 91-94
• 92 Asymbekova E, Bunin I, Pomerantsev E, Firstova M, Bakashvili N. [Effect of Ritmilen and allapinin on central hemodynamics and myocardial contractility of patients with heart rhythm disorders]. Kardiologiia 1987; 27: 68-71
• 93 Vizir A, Grigorʼeva Z, Stepanova I, Vizir V. [Membrane-stabilizing preparations in the treatment of patients with heart rhythm disorders of different etiologies]. Vrach Delo 1991; 10: 32-36
• 94 Pevzner AV, Bakalov SA, Efremova IY, Krutanov IB, Maikov EB, Dianova YF, Panteleimonov AV, Golitsyn SP. Comparative antiarrhythmic efficiency of allapinin, etacizin and bonnecor in patients with paroxysmal ventricular tachycardia assessed by Holter ECG. Kardiologiya 1995; 35: 19-24
• 95 Pevzner A, Bakalov S, Malakhov V, Krutanov I, Efremova I, Maykov E, Panteleymonov A, Golitsin S. Results of the use of allapinin, aethacizin, and bonnecor in treatment of patients with paroxysmal ventricular tachycardias under intracardiac electrophysiological control. Kardiologiya 1996; 36: 52-57
• 96 Koshumbaeva K, Belokopyt I, Tulenov M, Berdykhanova R. Comparative efficacy of class 1 antiarrhythmic drugs tachmalcor, propafenone and allapinin in paroxysmal supraventricular tachycardia. Kardiologiya 2000; 40: 23-25
• 97 Sokolov S, Dzhakhangirov F. [Antiarrhythmic drug allapinin: review of results of clinical investigation]. Kardiologiia 2001; 42: 96-102
• 98 Sokolov SF, Bakalov SA, Mironova NA, Rogova MM, Malkina TA, Golitsyn SP. [Efficiency and safety of allapinin in short- and long-term treatment of patients with normal heart and ventricular premature beats]. Kardiologiya 2014; 54: 20-26
• 99 Vakhitova YV, Farafontova EI, Khisamutdinova RY, Yunusov VM, Tsypysheva IP, Yunusov MS. A study of the mechanism of the antiarrhythmic action of Allapinin. Russ J Bioorg Chem 2013; 39: 92-101
• 100 Huang X, Yang Y, Zhu J, Dai Y, Pu J. The effects of a novel anti-arrhythmic drug, acehytisine hydrochloride, on the human ether-a-go-go related gene K channel and its trafficking. Basic Clin Pharmacol Toxicol 2009; 104: 145-154
• 101 Gao X, Zhu J, Yang Y, Li J, Yang Z, Liu J. Acehytisine hydrochloride injection phase II clinic trial group investigators. Efficacy of intravenous acehytisine hydrochloride versus propafenone on terminating paroxysmal supraventricular tachycardia: a double-blinded, randomized multi-center study. Zhonghua Xin Xue Guan Bing Za Zhi 2006; 35: 151-154
• 102 Yang YM, Zhu J, Gao X, Yin YL, Hao YX, Liu JH. [Effect of Guanfu Base A in patients with ventricular arrhythmias]. Zhonghua Xin Xue Guan Bing Za Zhi 2006; 34: 329-332
• 103 Turkington C, Mitchell DR. The encyclopedia of poisons and antidotes. New York: Infobase Learning; 2010
• 104 Trestrail JH. Criminal poisoning: Investigational guide for law enforcement, toxicologists, forensic scientists, and attorneys. New Jersey: Humana Press; 2007
• 105 Rowling JK. Harry Potter and the philosopherʼs stone. London: Pottermore Limited; 2012
• 106 Pharmacopoeia Commission of Peopleʼs Republic of China. Pharmacopoeia of the Peopleʼs Republic of China 2005. Beijing: Peopleʼs Medical Publishing House; 2005
• 107 Lin CC, Chan TYK, Deng JF. Clinical features and management of herb-induced aconitine poisoning. Ann Emerg Med 2004; 43: 574-579
• 108 Chan TYK. Incidence of herb-induced aconitine poisoning in Hong Kong: impact of publicity measures to promote awareness among the herbalists and the public. Drug Saf 2002; 25: 823-828
• 109 Chan TYK. Aconite poisoning following the percutaneous absorption of Aconitum alkaloids. Forensic Sci Int 2012; 223: 25-27
• 110 Du Q, Pan JH, Yan GJ. Determination of ester-series alkaloid and total alkaloid in complex prescription monkshood plaster. Li Shi Zhen Med Materia Medica Res 2008; 19: 158-160
• 111 Lai C, So Y, Hau L. Aconite poisoning in camouflage. Hong Kong Med J 2006; 12: 456-459
• 112 Fujita Y, Terui K, Fujita M, Kakizaki A, Sato N, Oikawa K, Aoki H, Takahashi K, Endo S. Five cases of aconite poisoning: toxicokinetics of aconitines. J Anal Toxicol 2007; 31: 132-137
• 113 Lin CC, Phua DH, Deng JF, Yang CC. Aconitine intoxication mimicking acute myocardial infarction. Hum Exp Toxicol 2011; 30: 782-785
• 114 Zhou G, Tang L, Zhou X, Wang T, Kou Z, Wang Z. A review on phytochemistry and pharmacological activities of the processed lateral root of Aconitum carmichaelii Debeaux. J Ethnopharmacol 2015; 160: 173-193
• 115 Peter K, Schinnerl J, Felsinger S, Brecker L, Bauer R, Breiteneder H, Xu R, Ma Y. A novel concept for detoxification: complexation between aconitine and liquiritin in a Chinese herbal formula (ʼSini Tang ). J Ethnopharmacol 2013; 149: 562-569
• 116 Liu CC, Cheng ME, Duan HY, Peng HS. [Reasearch on evolution and transition of processing method of fuzi in ancient and modern times]. Zhongguo Zhong Yao Za Zhi 2014; 39: 1339-1344
• 117 Wen RQ, Li DH, Zhao X, Wang JB, Zhao YL, Zhang P, Sun ZY, Yan D, Xiao XH, Ren YZ, Li F, Du J, Zhou HY. [Rationality of the processing methods of aconiti lateralis radix (Fuzi) based on chemical analysis]. Yao Xue Xue Bao 2013; 48: 286-290
• 118 Deore SL, Moon KV, Khadabadi SS, Deokate UA, Baviskar BA. Evaluation of toxicity of ʼVatsanabhaʼ (Aconitum ferox, Ranunculaceae) Before and After Shodhana. J Young Pharm 2013; 5: 3-6
• 119 Arai YC, Yasui H, Isai H, Kawai T, Nishihara M, Sato J, Ikemoto T, Inoue S, Ushida T. The review of innovative integration of Kampo medicine and Western medicine as personalized medicine at the first multidisciplinary pain center in Japan. EPMA J 2014; 5: 10
• 120 Chan TY. Causes and prevention of herb-induced aconite poisonings in Asia. Hum Exp Toxicol 2011; 30: 2023-2026
• 121 Chrubasik J. The role of Kampo in Germany. In: Oyama T, Smith G, editors Pain and Kampo. Tokyo: Springer; 1994: 173-177
• 122 Burrows GE, Tyrl RJ. Toxic plants of North America. New Jersey: John Wiley & Sons; 2012