Aconitum in Traditional Chinese Medicine-A valuable drug or an unpredictable risk?

Aconitum species have been used in China as an essential drug in Traditional Chinese Medicine (TCM) for 2000 years. Reviewing the clinical application of Aconitum, their pharmacological effects, toxicity and detoxifying measures, herb–herb interactions, clinical taboos, famous herbal formulas, traditional and current herbal processing methods based upon a wide range of literature investigations serve as a case study to explore the multidisciplinary implications of botanicals used in TCM. The toxicological risk of improper usage of Aconitum remains very high, especially in countries like China, India and Japan. The toxicity of Aconitum mainly derives from the diester diterpene alkaloids (DDAs) including aconitine (AC), mesaconitine (MA) and hypaconitine (HA). They can be decomposed into less or non-toxic derivatives through Chinese traditional processing methods (Paozhi), which play an essential role in detoxification. Using Paozhi, the three main forms of processed aconite – Yanfuzi, Heishunpian and Baifupian – can be obtained (CPCommission, 2005). Moreover, some new processing techniques have been developed in China such as pressure-steaming. The current development of fingerprint assays, in particular HPLC, has set a good basis to conduct an appropriate quality control for TCM crude herbs and their ready-made products. Therefore, a stipulation for a maximum level of DDA content of Aconitum is highly desirable in order to guarantee the clinical safety and its low toxicity in decoctions. Newly developed HPLC methods have made the accurate and simultaneous determination and quantification of DDA content interesting.     

The Classification and Application of Toxic Chinese Materia Medica

Many important drugs in the Chinese materia medica (CMM) are known to be toxic, and it has long been recognized in classical Chinese medical theory that toxicity can arise directly from the components of a single CMM or may be induced by an interaction between combined CMM. Traditional Chinese Medicine presents a unique set of pharmaceutical theories that include particular methods for processing, combining and decocting, and these techniques contribute to reducing toxicity as well as enhancing efficacy. The current classification of toxic CMM drugs, traditional methods for processing toxic CMM and the prohibited use of certain combinations, is based on traditional experience and ancient texts and monographs, but accumulating evidence increasingly supports their use to eliminate or reduce toxicity. Modern methods are now being used to evaluate the safety of CMM; however, a new system for describing the toxicity of Chinese herbal medicines may need to be established to take into account those herbs whose toxicity is delayed or otherwise hidden, and which have not been incorporated into the traditional classification. This review explains the existing classification and justifies it where appropriate, using experimental results often originally published in Chinese and previously not available outside China. Copyright © 2013 John Wiley & Sons, Ltd.     

《普济方》乌头类中药儿童应用探讨

目的:乌头类中药药理活性广泛,但其临床中毒剂量与治疗剂量接近,《普济方》是我国最大的方书,分析与研究《普济方》婴孩篇乌头类中药方剂,总结乌头类中药儿童的用药规律和特点,为指导乌头类中药在儿童临床运用提供参考。方法:收集和整理《普济方》婴孩篇乌头类中药方剂,建立乌头类中药处方数据表,统计与分析方剂中的乌头类中药、剂量、剂型、适应症及炮制品等。结果:共收集《普济方》婴孩篇中含附子、川乌、草乌、乌头、天雄5种乌头类中药方剂总计300首,64. 45%的处方以附子入药。治疗疾病种类涉及13种,主要是诸风、惊风(包括急慢惊风、慢脾风等)、吐泻、下痢、大小便淋秘等。乌头类中药用药剂量在3 g以下的方剂占有记载剂量的95. 10%,儿童乌头类中药方剂以内服剂型为主,且48. 33%为丸剂,同时丸剂用药剂量高于散剂、汤剂。使用炮制品的方剂有169首,占54. 17%,采用特殊服法的方剂有170首,"米饮服"所占比例最高。结论:儿童乌头类中药方剂占《普济方》比例较少,用药剂量较轻,且不同方剂剂型用药剂量存在差异。通过研究乌头类有毒中药在儿童方剂中的应用,临床应从辨证遣药、严格控制用药剂量和疗程、注重配伍、服药禁忌,加强临床用药监护等方面建立乌头类中药临床用药警戒,为儿童安全、有效地合理使用乌头类有毒中药提供参考。     

乌头类中药毒性及现代毒理学研究进展

乌头类中药是一类常用有毒中药材,在我国有悠久的药用历史。其所含主要成分乌头碱、新乌头碱、次乌头碱等具有显著的药理活性,同时也是其毒性成分。由于其治疗剂量和中毒剂量非常接近,临床治疗窗较窄,在临床使用过程中不良反应和中毒事件频频发生,限制其广泛应用。研究炮制或配伍对乌头急性毒性的影响,并深入了解其毒性产生的机制,对于进一步开发乌头新型制剂、指导临床更加安全合理地使用乌头类中药及其安全性评价等具有十分重要的意义。通过对近年来乌头类中药毒性成分、急性毒性及与毒性相关机制的研究文献进行综述,为临床安全使用乌头类中药提供科学依据。     

基于中药模拟炮制的乌头属植物水解机制及液质联用测定方法的研究进展

生物碱是大多数乌头属药用植物的主要有效成分,具有较高的药理活性和药用价值,但也是其主要的毒性成分,为便于对乌头属植物水解产物的深入研究,主要从中药模拟炮制现状、乌头属植物所含的生物碱种类、水解机制研究现状及液质联用方法几个方面进行综述。     

超分子“印迹模板”理论解析中药五味

中药五味理论是中医药学核心内容,表征中药成分群的特征性质,用于指导临床。但五味怎样表征众多成分群、药材划分五味的标准,以及五味归五脏等科学问题仍未解释清楚。分析总结了中药五味的历史沿革和研究现状,以超分子"印迹模板"理论解析中药五味:人与中药都是生物超分子体,中药作为天然超分子"印迹模板"聚集体,经口服或注射后必然寻找到与自身"印迹模板"相吻合的人体脏器的超分子主体,发生自识别、自组织、自组装与自复制作用,从而产生特异性的药效,宏观上表现出中药五味归五脏现象。因此,通过对中药五味体内外各成分群超分子"印迹模板"特征、作用规律及其网络药理学的定性定量研究,建立"中药成分群-味蕾超分子孔穴结构-经络脏腑孔穴"关联研究方法,宏观与微观相结合研究中药五味。超分子化学理论与中医药相结合,必将推动中医药的发展,实现中医药的现代化。     

本草学毒性理念的源流探考与论述范式的诠解

本草学是在传统医学理论指导下对传统"药"学的统称。中药的毒性理论蕴含于本草学药性理论之中,其论述范式则指撰写本草学著作所应用的指导原则。毒性理论的论述范式是经《神农本草经》《新修本草》《证类本草》的传承逐渐形成的,其形成在汉代"生生不息"观念的凝结中又涵摄了药性、毒副作用、药材基原、药材制备及配伍等复杂面向。经探考发现传统的"有故无殒"药性作用部分应回归四气及气味厚薄的记述;不当的药材基原部分应统属于药材来源的管控;特殊体质的不良服药反应不应归于毒性的记述,因剂量不宜或服用方法不当所产生的不良反应应回归到国家相关部门建议的项目之下;毒性分级分类的标准须有现代毒理的研究为基础同时严格限制使用剂量与适用范围。这将有助于重新建构既兼顾中药用药安全又能最大限度发挥中药特色的现代本草学。     

川陕滇乌头属药用植物资源调查

目的 调查四川、陕西、云南乌头属药用植物及附子药材主产区的资源、栽培及产地加工现状,为乌头类药材的资源保护、规范栽培、产地加工、质量控制等提供依据。方法 通过文献调研及走访产地、市场对四川、陕西、云南乌头属药材产区的乌头属植物种类、分布和附子药材情况进行调查。结果 四川、陕西、云南乌头属药用植物品种较多,分别有67、63、10个种。乌头属药材主要来自人工栽培,但基原复杂;乌头属药材新种植区域产地加工欠规范,部分存在品种间掺混现象。结论 四川、陕西、云南乌头属药用植物资源丰富,应加强资源保护、种源鉴定和新品种选育,大力推广规范栽培及产地加工,规范流通市场,建立质量溯源体系,保证用药安全。     

中药挥发油质量控制的现状、问题与对策

中药挥发油的质量稳定是保证其发挥临床疗效及安全性的前提。目前,中药挥发油的质量参差不齐,同种药材不同产地、同种药材不同厂家、同种药材不同批次的中药挥发油都存在较大质量差异。对中药挥发油质量控制的现状及问题进行了分析,并提出了中药材种植与品种规范化、加工过程规范化、投料部位标准化、提取工艺标准化、提取设备标准化等对策,同时简要分析了挥发油在中成药中的应用现状及质量控制,以期为有效控制中药挥发油及其中成药的质量提供参考。     

治疗咳嗽中药专利复方的用药规律分析

通过分析近20年中药治疗咳嗽的专利现状,探讨中药在治疗咳嗽过程中的用药规律。在SIPO专利检索平台和中国知网的专利数据库对中药治疗咳嗽的专利进行检索,采用Clementine12.0软件进行关联性和高频中药网络分析,分析治疗咳嗽中药和配伍中药药对的使用规律。在治疗咳嗽的316首中药专利中,中药复方中使用频数最高的中药为甘草,其他使用频数较高的中药有桔梗、麻黄、陈皮、半夏等;使用的化痰止咳平喘类药偏多。常用的药对为甘草-桔梗、甘草-陈皮、半夏-甘草、麻黄-甘草。通过对中药频数、药类、药对、关联规则、高频中药网络的分析,结合中医理论可以揭示咳嗽中药复方的配伍规律,为临床用药提供依据。     

菜部类、谷部类和其他药食同源中药安全性评价研究进展

药食同源是古人在食物和药物之间发现总结的智慧结晶。虽然药食同源中药的活性成分、药理作用已有大量文献报道，但有关其安全性方面的报道相对较少。古代本草，尤其是食物类本草著作记载了大量的药食同源中药，并对来源、品种、功效、禁忌、用法与用量等进行了系统的概述。通过系统地查阅和整理相关文献资料，对药食同源中药的安全性或不良反应进行了综述，为其食疗和保健研究提供了宝贵的依据。     

The rise of traditional Chinese medicine and its materia medica: A comparison of the frequency and safety of materials and species used in Europe and China

Ethnobotanical relevance

Due to the global rise in the use of traditional Chinese medicine (TCM), Chinese materia medica (medicinal materials, or CMM) are giving cause for concern over their evidence base, safety/possible toxicity, questionable quality and use of endangered species of both animals and plants. However, little if anything is actually known about the range of species used to produce CMM used in Europe and even in China. This study represents the first attempt to identify and compare the most important CMM used in both regions, to begin the process of assessing the risks to public health and possible future benefits.

Materials and methods

Data were collected from a convenience sample of TCM practitioners in the EU and mainland China, using a paper/online survey. Among other questions, respondents were asked (1) which conditions they most commonly treated using CMM and the likelihood of them using herbal manufactured products and decoctions in addition to raw herbs; (2) the perceived frequency with which they observed adverse events to CMM; (3) the frequency and reasons for use of 1 herbal formula and 6 specific individual herbs; (4) an open question about other CMM they used, including materials of non-plant origin. Data were entered into PASW statistics package and analysed using frequency tables, cross-tabulations and chi-squared tests to compare EU and Chinese results.

Results

From a total of 747 useable questionnaires (420 from China, 327 from the EU) of those responding from the EU, TCM was generally more commonly used for obstetric/gynaecological and dermatological conditions, compared to neurological and gastrointestinal diseases in China. Disorders treated by Chinese practitioners were more varied, and often more serious, than those treated by their European counterparts, and the range of materials used in China was wider. The potential for toxicity was not high in either region, but although greater in China due to the use of more potent CMM, the incidence of side effects was perceived to be higher by EU practitioners.

Conclusions

Very few of the species used to prepare CMM in the EU in this study give rise to safety concerns from what is known from the scientific and other literature, and in China only a few toxic CMM appear to be commonly used, some of them only after processing and mainly for serious disorders. The main cause for concern is likely to be interaction with prescribed medication, especially in central nervous system and cardiovascular conditions where drug interactions have previously been reported most frequently and which would currently be more applicable in China than Europe.     

Evidence-based toxicity evaluation and scheduling of Chinese herbal medicines

Ethnopharmacological relevance

While there is an increasing number of toxicity report cases and toxicological studies on Chinese herbal medicines, the guidelines for toxicity evaluation and scheduling of Chinese herbal medicines are lacking.

Aim

The aim of this study was to review the current literature on potentially toxic Chinese herbal medicines, and to develop a scheduling platform which will inform an evidence-based regulatory framework for these medicines in the community.

Materials and methods

The Australian and Chinese regulations were used as a starting point to compile a list of potentially toxic herbs. Systematic literature searches of botanical and pharmaceutical Latin name, English and Chinese names and suspected toxic chemicals were conducted on Medline, PubMed and Chinese CNKI databases.

Results

Seventy-four Chinese herbal medicines were identified and five of them were selected for detailed study. Preclinical and clinical data were summarised at six levels. Based on the evaluation criteria, which included risk–benefit analysis, severity of toxic effects and clinical and preclinical data, four regulatory classes were proposed: Prohibited for medicinal usage, which are those with high toxicity and can lead to injury or death, e.g., aristolochia; Restricted for medicinal usage, e.g., aconite, asarum, and ephedra; Required warning label, e.g., coltsfoot; and Over-the-counter herbs for those herbs with a safe toxicity profile.

Conclusion

Chinese herbal medicines should be scheduled based on a set of evaluation criteria, to ensure their safe use and to satisfy the need for access to the herbs. The current Chinese and Australian regulation of Chinese herbal medicines should be updated to restrict the access of some potentially toxic herbs to Chinese medicine practitioners who are qualified through registration.     

经典名方中“术”的本草考证

中药经典名方的研发是促进中医药继承创新和提高临床服务水平的重要途径,经典名方中药材基原的确定对其研发尤为重要,是保证质量、药效及安全性的源头。"术"入药历史悠久,《神农本草经》中列为上品,为经典名方中常用中药。但南北朝以前"苍术""白术"均可作为"术"入药,未做明确区分,致使本草考证是含"苍术""白术"经典名方研发中的难题。结合历代本草,从植株形态、产地、性味、功效等方面梳理"术"的历史变迁,以期为"术"的本草考证以及经典名方的研发提供参考借鉴。     

乌头类中药毒代动力学及代谢组学研究进展

乌头类中药是一类常用中药材,含有多种生物活性物质,具有很高的药用价值,然而毒性极强,其主要毒性成分是乌头碱、新乌头碱、次乌头碱,同时也是有效成分,因此临床使用的安全性应受到广泛关注。随着药物开发研究的不断深入,人们已经不满足于仅仅了解药物的毒性,更迫切地需要了解其致毒机制及毒性产生和发展的规律性,以便对药物的安全性作出科学合理的评价,因此毒代动力学及代谢组学评价已逐渐成为创新药物评价的一项重要内容。建立科学、客观、规范的乌头类中药安全评估体系,正确评估和运用其毒性,是药物性能开发的重要内容。作者通过近年来对乌头类药物的毒代动力学和代谢组学研究进展进行综述,提出加强乌头类药物安全性评价研究工作,尽快建立科学,规范的安全评价体系,使民族瑰宝发挥出更大的优势。     

款冬花药材质量评价方法的研究现状及分析

款冬花Farfarae Flos是中医临床和中药工业中常用药材,其质量直接关系到中医临床用药的安全性和有效性。从性状、显微鉴别、薄层鉴别、定量测定、指纹图谱、商品规格标准等方面对款冬花的质量评价方法及研究现状进行综述和分析,为款冬花的质量标准提升提供必要的参考。     

《神农本草经》海洋中药品种考证

《神农本草经》是我国现存最早的一部中药学专著,现代学者在《神农本草经》学术思想上的研究成果颇丰,在药物研究方面多偏向于陆生和淡水生中药的研究,对于其中海洋中药的研究则相对较少,同时,所见文献对于《神农本草经》中海洋中药的品种数尚存争议。通过查阅历代本草文献,结合现代海洋药物研究及生物学、矿物学、历史地理等多种学科的研究成果,对《神农本草经》所载海洋中药的品种分类、生境分布、不同文献对《神农本草经》海洋中药品种与数量记述的差异等进行比较分析,并对历来存有异议的11个品种进行深入的考证,提出《神农本草经》共收载海藻、牡蛎、大盐等12味海洋中药,为《神农本草经》海洋中药的学术研究提供了有益的参考。     

蟾酥的研究进展

蟾酥由蟾蜍表皮腺体的分泌物经干燥而成。作为一种传统中药,其所含化学成分复杂,能清热解毒、醒脑开窍、化结溃坚;具有降压、增强心肌收缩力、增加冠状动脉流量、抗肿瘤、麻醉等药理作用。临床中广泛用于心血管系统、呼吸系统、五官、外科等疾病的治疗;作为有毒中药,其量效关系、毒性成分、中毒剂量和毒理机制等问题亦不容忽视。试从蟾酥的化学成分、药理作用及其机制、毒理作用、不良反应、炮制工艺、药动学等方面对其进行初步总结,为深入研究蟾酥的药理作用及复方制剂提供参考。     

夏天无与延胡索的比较分析及其质量标志物预测

夏天无与延胡索药材的源植物同为紫堇属植物,均收载于《中国药典》2015年版一部,性味功效相近,但实际临床应用侧重点有所不同。通过查阅文献,从传统功效、化学成分、药理作用等方面比较分析夏天无与延胡索的异同;并基于质量标志物(Q-marker)的核心概念,从生源途径、药效、药动学和体内过程以及传统药性药效等方面对夏天无质量标志物进行预测分析,为建立和完善其药材质量标准提供理论依据。     

含药肠吸收液:一种新的中药体外药理实验方法

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