Aconitum Alkaloid Poisoning Related to the Culinary Uses of Aconite Roots

Aconite roots (roots or root tubers of the Aconitum species) are eaten as root vegetables and used to prepare herbal soups and meals, mainly for their purported health benefits. Aconite roots contain aconitine and other Aconitum alkaloids, which are well known cardiotoxins and neurotoxins. To better understand why Aconitum alkaloid poisoning related to the culinary uses of aconite roots can occur and characterize the risks posed by these “food supplements”, relevant published reports were reviewed. From 1995 to 2013, there were eight reports of aconite poisoning after consumption of these herbal soups and meals, including two reports of large clusters of cases (n = 19–45) and two reports of cases (n = 15–156) managed by two hospitals over a period of 4.5 to 5 years. The herbal formulae used did not adhere to the suggested guidelines, with regarding to the doses (50–500 g instead of 3–30 g per person) and types (raw instead of processed) of aconite roots used. The quantities of Aconitum alkaloids involved were huge, taking into consideration the doses of aconite roots used to prepare herbal soups/meals and the amounts of aconite roots and herbal soups/meals consumed. In a large cluster of cases, despite simmering raw “caowu” (the root tuber of A. kusnezoffii) in pork broth for 24 h, all 19 family members who consumed this soup and boiled “caowu” developed poisoning. Severe or even fatal aconite poisoning can occur after consumption of herbal soups and foods prepared from aconite roots. Even prolonged boiling may not be protective if raw preparations and large quantities of aconite roots are used. The public should be warned of the risk of severe poisoning related to the culinary and traditional medicinal uses of aconite roots.     

附子抗心律失常作用机制研究进展

心律失常是一类较常见的心血管系统疾病,种类多、病因复杂,严重可致死。临床药物治疗多以β受体阻滞剂和离子通道阻滞剂为主,但也伴有一定毒副作用。附子是毛茛科植物乌头子根的加工品,味辛、甘,性大热,归心、肾、脾经,有抗心律失常的功能。目前,关于附子及配伍方剂拮抗心律失常的研究日趋增加。本文通过查阅文献,在阐述附子及配伍方剂对心律失常的拮抗作用上,进一步分析两者抗心律失常的机制,为后续附子的安全使用及研究提供参考。     

附子心脏毒性及配伍减毒增效机制研究进展

附子来源于毛茛科植物乌头Aconitum carmichaeli Debx.,最主要的毒性反应表现为心脏毒性和神经毒性,其中心脏是主要的靶器官之一。目前普遍认为附子所致心脏毒性是由双酯型二萜生物碱直接或间接作用于心脏的结果,其毒性机制与Ca²⁺超载、脂质过氧化反应、细胞凋亡以及迷走神经兴奋性增高有关。研究发现附子与其他传统中草药配伍能通过影响体内代谢过程、抗Ca²⁺超载、抗氧化应激、抗凋亡等机制发挥减毒增效作用。就近年来国内外对附子心脏毒性及配伍减毒增效相关机制的研究进展进行综述,以期为附子的深入研究和临床安全用药提供参考。     

附子新型炮制品中乌头类生物碱测定及其强心作用研究

目的 比较附子新型炮制品与传统炮制品中乌头碱类水平及强心作用,为附子炮制工艺改进提供药理学依据。方法 采用高效液相(HPLC)色谱法测定生附子及黑顺片、高温片、高压片、微波片4种附子炮制品及其煎煮液中6种乌头类生物碱水平;应用Langendorff大鼠离体心脏灌流法,测定附子4种炮制品对心率(HR)、左心室收缩压(LVSP)、舒张末压(LVEDP)、左心室内压变化速率(±dp/dt_max)的影响,分析其强心作用。结果 与生附子比较,附子经炮制后,毒性成分双酯型生物碱减低,单酯型生物碱逐渐增加;与黑顺片比较,高压片中生物碱得到最大限度保留,单酯型生物碱水平高于黑顺片,双酯型生物碱水平较低,说明附子高压炮制是一种“低毒高效”的工艺;而高温片和微波片中单、双酯型生物碱水平均有所降低,其成分有一定的流失;4种炮制品煎煮液中6种生物碱溶出率与炮制品中生物碱水平呈正相关。与对照组比较,4种炮制品均能够显著升高离体大鼠心脏的HR、LVSP、±dp/dt_max,降低LVEDP,且呈一定剂量相关性;与黑顺片组比较,3种新型炮制品HR、LVSP、LVEDP、±dp/dt_max均差异不显著;在相同剂量下,高压片中HR、LVSP、±dp/dt_max值最高,LVEDP值较低。结论 附子高压炮制工艺是一种“高效低毒”炮制工艺,且强心作用效果较好。     

附子配伍原则的电喷雾质谱研究

目的从化学角度探讨附子配伍的原则。方法利用电喷雾质谱分析和比较生附子及其复方中药煎煮液中二萜类生物碱的变化规律；测定附子及其他中药煎煮液的pH值并用电喷雾质谱考察酸性对药材中乌头碱水解的影响。结果生附子单煎煮及与甘草共煎后双酯型乌头生物碱大部分发生水解，生附子与半夏或五味子共煎生物碱水解受抑制，生附子和甘草单煎液的酸性远低于半夏或五味子单煎液，中乌头碱在酸性条件下不水解。结论酸性是影响乌头碱类双酯型生物碱水解的重要因素，强酸条件下水解受抑制，附子煎煮液毒性增加。     

乌头中主要生物碱的高效液相色谱测定

用高效液相色谱分离、测定乌头及附子中一些主要生物碱。生药的乙醚提取物在十八烷基键合相柱上,用甲醇—水—氯仿—三乙胺(70:30:2:0.1)作流动相,中乌头碱、乌头碱及次乌头碱与其它杂质能很好分离。以β-甲基萘作内标化合物,用峰高比测定各生物碱含量。曾测定了不同品种、不同产地及不同加工炮制方法的一些样品,其生物碱组成及比例相差较大。     

The relationship between growth of the aerial part and alkaloid content variation in cultivated <Emphasis Type="Italic">Aconitum carmichaeli</Emphasis> Debeaux

Processed root of aconite, Aconitum carmichaeli Debeaux—known as bushi in Japan—is indispensable for treating diseases among elderly persons in Japanese and Chinese traditional medicine. Its active component is bushi diester alkaloid (BDA), which consists of aconitine (ACO), mesaconitine (MES), hypaconitine (HYP), and jesaconitine (JES). Since an overdose of BDA results in severe side effects, the BDA content should be within safe limits. However, the BDA content of raw aconite root, even that produced by standard cultivation procedures, varies greatly. In this study, to clarify the cause of BDA variation, we examined the weight and BDA content of each part of cultivated A. carmichaeli: the aerial part, the mother tuberous root (MT), the daughter tuberous root (DT), and the rootlet (RL). We found the following positive relationships: between aerial part weight and DT weight, aerial part weight and BDA content in stem of apex, and BDA content in stem of apex and total BDA of DT attached to the plant. Furthermore, DT belonging to a higher weight group showed less BDA content variation. In addition, BDA of DT and those of MT and RL differ in both content and composition. In conclusion, it was suggested that the weight or the size of the aerial part was a good marker for monitoring BDA content and its variation in the tuberous root, and it was found to be desirable to prevent mixing MT and RL at harvest.     

乌头中毒1例的救治

患者女,57岁,因患类风湿关节炎服用超剂量附子、川乌、草乌等中药方剂治疗,1d后出现全身麻木、心悸、恶心、呕吐等症状,诊断为乌头碱中毒,即予阿托品0.5mg肌内注射,后静脉滴注1mg,经对症处理后症状消失。     

附子及附子配伍干姜对腺嘌呤所致慢性肾衰小鼠肾功能的影响

目的：研究中药附子及附子配伍干姜对腺嘌呤所致小鼠慢性肾衰的疗效,并初步探讨其作用机制。方法：将雄性ICR小鼠随机分为正常对照组、模型组、低剂量附子组、高剂量附子组、低剂量附子＋干姜组和高剂量附子＋干姜组。正常对照组小鼠灌胃给予蒸馏水;其余各组小鼠灌胃给予腺嘌呤（第1周和第2～4周的给药剂量分别为250和130 mg.kg-1,均为每2天给药1次）,低剂量附子组、高剂量附子组、低剂量附子＋干姜组和高剂量附子＋干姜组小鼠另分别灌胃给予相应的水煎液,每天1次。实验过程中,记录各组小鼠的一般情况,并于实验结束时,对小鼠血清肌酐、尿素氮、乳酸和乳酸脱氢酶,以及肾组织谷胱甘肽、谷丙转氨酶、谷草转氨酶和丙二醛的含量进行测定,并记录附睾精子数。结果：与正常对照组相比,模型组和各给药组小鼠体重下降,摄食量减少,饮水量升高;高剂量附子组和低剂量附子＋干姜组小鼠饮水量明显低于模型组小鼠。模型组小鼠消瘦、萎靡、被毛发黄干枯不齐,部分死亡;高剂量附子＋干姜组和低剂量附子＋干姜组小鼠被毛白净有光泽,且活动性更强。高剂量附子水煎液,高剂量附子＋干姜水煎液,以及低剂量附子＋干姜水煎液对小鼠生化指标具有显著改善作用,可降低肾系数以及血清肌酐、尿素氮、乳酸和乳酸脱氢酶水平,提高精子数;可降低小鼠肾组织GSH水平,升高MDA水平;高剂量附子组和高剂量附子＋干姜组小鼠肾组织ALT水平,以及高剂量附子＋干姜组和低剂量附子＋干姜组小鼠肾组织AST水平均显著高于模型组;低剂量附子组小鼠除个别指标外,无明显的改善。结论：高剂量附子水煎液对腺嘌呤所致慢性肾功能衰竭小鼠肾功能具有一定保护作用,与干姜配伍后其疗效增加,毒性降低。     

Causes and prevention of herb-induced aconite poisonings in Asia

The recent reports from Hong Kong, Taiwan, China and Korea were reviewed to determine the causes and prospects for prevention of herb-induced aconite poisonings. The contributory factors included overdose (use of greater than the recommended doses), faulty processing (after harvest and during decoction), use of tincture (herbal medicinal wine), use of crude aconite roots (for preparing decoction, proprietary medicines and tincture), lack of standardisation in processing of aconite roots and preparation of tincture and proprietary medicines, unsupervised use of aconite roots and contamination or mix-up with aconite roots. As tincture (herbal medicinal wine) made from aconite roots contains a much larger amount of Aconitum alkaloids, the public should be strongly discouraged from making their own and taking it by mouth. Aconite roots should only be used after post-harvest processing and proper decoction. The public should be educated on the hazards from unsupervised use and improper decoction of processed aconite roots. There should be regular publicity measures to promote awareness among the herbalists and to publicise the risk of serious cardiotoxicity if the recommended doses of processed aconite roots are exceeded. The processing of aconite roots and their proprietary preparations should be standardised. Quality control of processed aconite roots and their proprietary preparations should be strengthened. National reporting or monitoring systems can be used to identify the causes of aconite poisonings and assess the impact of preventive measures.     

舒心口服液的定性鉴别

本文采用薄层层析法对复方中药制剂舒心口服液中的附子、丹参、川芎、蟾酥等４味药进行定性鉴别,方法简便结果准确。     

The effect of planting depth,disbudding, and root pruning on root weight and aconite alkaloid content of the tuberous root of aconite

The tuberous root of aconite, Aconiti tuber, contains tonic but poisonous aconite alkaloids, such as aconitine, hipaconitine and mesaconitine. The standardization of the cultivation protocols must be established, since the quality of the crude drug, especially the content of aconite alkaloids, is influenced by cultivation conditions. Here, we report the effects of planting depth, disbudding and root pruning on the content of the aconite alkaloids as well as on the weight of the root tuber of aconite. The daughter root tubers of shallow-planted plants showed a significantly higher content of aconitine, hipaconitine and sum of aconite alkaloids per unit weight than those of deeply planted root tubers (control group), while the average weight per root tuber was lower than that of the control group. The total weight of the daughter root tubers per plant of the disbudding group was significantly higher than that of other groups, including the root-pruning group whose average weight per tuber was the highest. In conclusion, disbudding is effective in achieving both higher content of aconite alkaloids and heavier total weight of the root tuber.     

附子对两种不同慢性肾病小鼠乳酸代谢的影响

目的：观察附子对两种不同慢性肾病模型小鼠乳酸代谢的影响,探讨附子的温阳、肾脏保护作用及与乳酸酸中毒的关系。方法：将雄性ICR小鼠随机分为7组：正常对照组、关木通模型组、关木通＋附子低剂量组、关木通＋附子高剂量组、腺嘌呤模型组、腺嘌呤＋附子低剂量组和腺嘌呤＋附子高剂量组。正常对照组灌胃等体积饮用水;关木通模型组灌胃给予7g·kg^-1·d^-1的关木通水煎剂,给药4天后停药3天,持续5周;腺嘌呤模型组先以250mg·kg^-1腺嘌呤隔天灌胃1次,持续1周,再以130mg·kg^-1腺嘌呤隔天灌胃1次,持续3周;关木通（腺嘌呤）模型＋附子低剂量组、关木通（腺嘌呤）模型＋附子高剂量组在造模的同时分别给予3、10g·kg^-1·d^-1的附子水煎剂。实验结束时,测定各组血清肌酐和尿素氮、乳酸含量及乳酸脱氢酶活性,以及肝、肾、睾丸的蛋白、乳酸含量和乳酸脱氢酶活性,并记录左肾、左睾系数及附睾精子数。结果：附子能显著降低两种肾病模型小鼠的血清尿素氮、乳酸含量、乳酸脱氢酶活性及左肾系数,显著提高精子数及肾脏蛋白含量;显著降低关木通模型小鼠的肝脏乳酸含量、肾脏的乳酸含量和乳酸脱氢酶活性,显著增加肾脏蛋白含量;显著增加腺嘌呤模型小鼠肾脏、皋丸的乳酸含量,提高肝脏、皋丸乳酸脱氢酶活性,降低肾脏乳酸脱氢酶活性及睾丸蛋白含量。附子剂量与药效呈一定的正相关性。结论：两种肾病模型均存在不同程度的乳酸酸中毒。附子对关木通致慢性马兜铃酸肾病的肾脏酸中毒的纠正情况最明显;而腺嘌呤致慢性肾衰模型虽血清乳酸含量显著升高,但肝、肾、睾丸中均未出现乳酸蓄积,相反,肾脏、睾丸中乳酸含量有所降低,附子也能使该模型小鼠的肝、肾乳酸含量和乳酸脱氢酶活性趋于正常值,提示附子的温阳、肾脏保护作用与调节乳酸代谢有关。     

Developing methods for analysis of the solid dosage form (capsules) of cardiocyclide

We have developed methods for the pharmaceutical analysis of the new domestic antiarrhythmic drug cardiocyclide in a solid dosage form (capsules). The main pharmacopoeial quality tests were carried out. The content of impurities in capsules was determined by thin-layer chromatography. UV spectrophotometry and gradient high-performance liquid chromatography were used for simultaneous assay, purity check, and quantitative analysis of the drug. The pharmacopoeial “Dissolution” test was carried out using UV spectrophotometry.     

不同品种附子生物碱和多糖含量的比较

目的:比较不同品种附子生物碱和多糖的含量。方法:采用酸性染料比色法测定附子总生物碱含量,反相高效液相色谱法测定双酯型生物碱含量,蒽酮-硫酸法测定多糖含量。结果:不同品种附子总生物碱和双酯型生物碱含量差异较大,附子多糖含量差异不显著。附子炮制后,黑附片中总生物碱、双酯型生物碱含量显著下降,附子多糖含量稍有增加。结论:本试验结果可为附子品种选育提供一定的科学依据。     

附子不同部位及其炮制品生物碱的含量比较△

目的:比较附子不同部位及其炮制品生物碱含量变化。方法:采用HPLC法同时测定附子不同部位及其炮制品中6种单、双酯型生物碱的含量,采用滴定法测定其总生物碱含量,分析其不同部位及其炮制品生物碱含量的变化。结果:单酯型生物碱大小依次为:制附子皮>黑顺片>白附片>附子皮>生附子,双酯型生物碱大小为:附子皮>生附子>制附子皮>黑顺片>白附片,总生物碱大小为:附子皮>生附子>制附子皮>黑顺片>白附片。结论:附子皮中生物碱的含量高,毒性大,为了保证其临床有效性与安全性,黑顺片与白附片临床应用应有所区分。     

附子炮制品及其煎煮液6种生物碱的含量测定

目的从附子炮制品来源、煎煮、配伍等方面评价其的安全性和有效性,为临床用药的提供一定参考依据。方法采用高效液相色谱法同时测定不同来源附子炮制品、单方煎煮和复方煎煮液中6种生物碱含量,综合评价附子炮制品的质量及煎煮、配伍对其有效成分和毒性成分的影响。结果不同来源黑顺片中6种生物碱含量差异较大,单酯型生物碱在0.303 5~1.394 8 mg/g之间,双酯型生物碱的含量在0~0.094 0 mg/g之间;炮附片生物碱含量偏低,单酯型生物碱在0.099 0~0.213 5 mg/g之间;两种炮制品经煎煮后,双酯型生物碱基本消失,单酯型生物碱含量也有所降低,其中黑顺片单煎液的溶出率为58.92%,炮附片单煎液的溶出率为87.87%,其复方煎煮液中单酯型生物碱含量均比单煎液偏高。结论 12批黑顺片中6种生物碱含量均符合药典要求,炮附片中生物碱含量偏低,不合格现象明显,煎煮液中双酯型生物碱含量基本消失,毒性更小,与甘草和干姜配伍后,有增效作用。     

Effect of shodhana treatment on chronic toxicity and recovery of aconite

Aconite is one of the poisonous plants used therapeutically in practice of Ayurveda after proper treatment called as 'Shodhana'. To determine the effect of Shodhana treatment on chronic toxicity and to assess the effect of recovery period after chronic toxicity of aconite. Raw aconite (RV), urine treated aconite (SM), and milk treated aconite (SD) were administered in 6.25 mg/kg dose in Charles Foster strain albino rats for 90 days for chronic toxicity. Six rats from each were kept for another 30 days without test drugs treatment to observe recovery from chronic toxicity. RV was found to be highly toxic in chronic exposure, SM had no apparent toxicity, but SD had mild toxicity in kidney. The toxicities of RV and SD were reversible, but sudden withdrawal of SM caused adverse effects, suggestive of tapering withdrawal. Shodhana treatments remove toxic effects from raw aconite. Chronic toxicity of aconite is reversible. Confirmed the arrangement of abstract.     

温脾汤中诸药不同组合及煎法对乌头碱含量的影响

目的：研究温脾汤中诸药的不同组合及煎法对乌头碱含量的影响。方法：以温脾汤为基础,配伍成不同组方,采用不同的提取工艺,应用紫外分光光法测定乌头碱的含量。结果：附子与干姜配伍能提高乌头碱含量,附子与大黄、甘草配伍能降低乌头碱含量,人参与附子配伍对乌头碱含量没有影响。结论：在温脾汤中,大黄、甘草能佐制附子的毒性,干姜能增强附子的功效。     

Multivariate statistical interpretation of laboratory clinical data

Laboratory aids are extensively used in the diagnosis of diseases, in preventive medicine, and as management tools. Reference values of clinically healthy people serve as a guide to the clinician in evaluating biochemical parameters. Determination of 21 biochemical parameters of healthy persons using standard methods of analysis. Cluster analysis and principal components analysis were applied on the above 21 biochemical parameters data. The application of a typical classification approach as cluster analysis proved that four major groups of similarity between all 21 clinical parameters are formed, which correspond to the authors assumption of the existence of several summarizing pattern of clinical parameters such as “enzyme,” “major component excretion”, “general health state,” and “blood specific” pattern. These patterns appear also in the subsets obtained by separation of the general dataset into “male”, “female”, “young”, and “adult” healthy groups. The results obtained from principal components analysis have additionally proved the validity of a similar assumption. The intelligent data analysis on the clinical parameter dataset has shown that when a complex system is considered as a multivariate one, the information about the system substantially increases. All these results support an idea that probably a general health indicator could be constructed taking into account the existing classification groups in the list of clinical parameters.