中药发酵技术传承与创新的探索

发酵作为一门极具特色和重要的中药炮制技术,其传承与发展应受到行业内的高度重视。传统中药发酵为自然发酵,因发酵过程靠经验掌控、易受到环境和季节变化的影响,质量难于控制且难以传承。而现代中药发酵技术在传统发酵技术的基础上结合发酵工程等现代生物技术,已逐渐发展起来,业内学者也对其进行了大量相关研究。但科学阐释中药发酵机制、规范中药发酵技术工艺及建立适合中药发酵特点的质量标准等是中药发酵技术研究面临的共性问题。本文在综述传统中药发酵技术概况及中药发酵技术现代研究情况的基础上,分析总结影响发酵技术传承与发展的关键技术问题,并从中药发酵技术的传承与创新两方面进行了探讨。提出中药发酵技术的传承需要正确认识中药发酵理论、挖掘中药发酵技术精髓和建立中药发酵数据库等建议;发酵技术的创新需要科学阐释中药发酵机制、客观化传承中药发酵经验、规范与创新发酵工艺、完善中药发酵质量标准和拓展中药发酵新品种等,为中药发酵技术的发展提供思路与借鉴。     

Omic techniques in systems biology approaches to traditional Chinese medicine research: present and future

Omic techniques have become key tools in the development of systems biology. As the holistic approaches underlying the practice of traditional Chinese medicine (TCM) and new tendencies in Western medicine towards personalised medicine require in-depth knowledge of mechanisms of action and active compounds, the use of omic techniques is crucial for understanding and interpretation of TCM development, especially in view of its expansion in Western countries. In this short review, omic applications in TCM research are reviewed which has allowed some speculation regarding future perspectives for these approaches in TCM modernisation and standardisation. Guidelines for good practice for the application of omics in TCM research are also proposed.     

基于多学科交叉的中药药效物质基础研究方法和思路概述

中药药效物质是揭示中药作用本质奥秘的关键,是中药安全性和质量控制的基础和核心,而中药及其复方多组分、多靶点、整体调节的作用特点,使其药效物质基础不明成为中医药现代化和国际化发展进程中的瓶颈之一.近年来,随着各学科研究方法和技术手段的不断发展和成熟,众多学科包括分析化学、中药药物化学、药理学、细胞生物学、系统生物学、生物信息学等不断引入中药研究.多学科的交叉整合实现了各学科之间的交流和良性互动,加速了中药研究和中药现代化的进程.该文通过对中药复方药效物质基础研究方法的探讨和总结,对多学科交叉整合的研究模式在中药药效物质基础研究中的应用进行综述,为中药及其复方药效物质基础的辨识提供参考.     

Metabolomics and Its Potential in Drug Discovery andDevelopment From TCM

Metabolomics, an omic science in systems biology, is the comprehensive profiling of metabolic changes occurring in living systems and has been widely used in the modern research of traditional Chinese medicine (TCM). TCM is a complex medical science, which reflects rich philosophical dialectical thought, puts the human body into a large system for observation and keeps human in a healthy status. For TCM aroused great interest in the whole world, herbs and Chinese medical formulae (CMF) as treatment methods have also been widely attention. Metabolomics represents a powerful way that provides a dynamic drawing of the phenotype of biological systems via the research of endogenous metabolites, and its methods are similar to those of TCM. This review summarizes the advantages of metabolomics, highlight the key role of biomarkers for drug discovery and development of TCM.     

细胞膜色谱及质谱联用技术在中药活性成分筛选中的应用

由于中药作用的整体性、成分和作用机制的复杂性,化学成分(群)作为中药及其复方制剂发挥治疗作用的物质基础,因此,采用多种方法分离分析中药及其复方中的化学成分一直是中药治病防病研究中一个有待解决的关键重要问题。传统方法存在操作繁琐、耗时耗事、浪费溶剂和样品的不可逆吸附等缺陷,并且分离过程中无法给出药理参数的基本信息,因而无法对活性成分进行高效准确定位。近年来从细胞层次研究药物成分与受体的结合为中药活性成分的筛选研究提供了一种新的途径。目前研究二者相互作用的方法之一—细胞膜色谱法(CMC),将现有色谱及质谱技术、细胞生物学与受体药理学结合起来,能够正确反映活性部位、活性成分与细胞膜及膜受体的相互作用,对复杂中药体系中有效部位筛选、活性成分的分离和高通量筛选具有独特优势。该文综述了CMC的原理、特点、中药活性成分筛选领域中的细胞膜模型及其与气相色谱-质谱(GC-MS)及液相色谱-质谱(LC-MS)联用的研究现状,并对其今后研究方法和未来的开发前景进行了探讨,为CMC在中医药领域的深入研究和开发利用提供理论依据和实践指导。     

Potential antifertility agents from plants: a comprehensive review

Ethnopharmacological relevance

Traditional medicines are practiced worldwide for regulation fertility since ancient times. This review provides a comprehensive summary of medicinal flora inhabitating throughout the world regarding their traditional usage by various tribes/ethnic groups for fertility regulation in females.

Materials and methods

Bibliographic investigation was carried out by analyzing classical text books and peer reviewed papers, consulting worldwide accepted scientific databases from the last six decades. Plants/their parts/extracts traditionally used for abortion, contraception, emmenagogue and sterilization purposes have been considered as antifertility agents. Research status of selected potential plant species has been discussed. Further, compounds isolated from plants with attributed fertility regulating potentials are also classified into three categories: (a) phytoconstituents with anti-implantation activity, (b) phytoconstituents with abortifacient activity and (c) phytoconstituents with contraceptive activity.

Results

577 plant species belonging to 122 families, traditionally used in fertility regulation in females, have been recorded, of which 298 plants have been mentioned as abortifacients (42%), 188 as contraceptives (31%), 149 as emmenagogues (24%), and 17 as sterilizers. Among 122 plant families, fabaceae constitutes 49.2%, asteraceae 40.98%, euphorbiaceae 19.7%, apiaceae 16.4%, poaceae 12.3%, labiateae 11.5%, and others in lesser proportion. Various plant parts used in fertility regulation include leaves (25%), roots (22%), fruits (15%), seeds (12%), stem/stem bark (37%), and flowers (4%). Some active compounds, isolated from about various plant species, have been reported to possess significant antifertility potential.

Conclusion

This review clearly indicates that it is time to increase the number of experimental studies to find out novel potential chemical entities from such a vast array of unexploited plants having traditional role in fertility regulation. Also, the mechanisms of action by which plant extracts and their active compounds exert antifertility effects remain to be studied.     

中医药临床研究中特殊伦理问题探讨

不同哲学理念下的东西方医学有不同的思维模式,本文针对中医药科学研究伦理审查过程中会遇到不同于西方医学的特殊伦理问题进行简要探讨,并提出应当构建符合中医药特色的伦理审查体系,制定中医药伦理审查标准,在推动中医药科研进步同时维护中医药受试者合法权利。     

基于网络药理学的中药治疗慢性阻塞性肺疾病作用机制研究进展＊

慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease， COPD）是一种高发病率、高致死率的慢性进行性疾病，对患者的肺功能、生活质量和经济负担产生严重的影响。中医药治疗COPD具有较好的疗效和优势，但作用机制尚未明确，网络药理学作为系统生物学的重要组成部分，通过构建“成分-靶点-通路-疾病”互作网络，从生物网络系统的角度阐释生命体对疾病刺激和药物治疗的反应，其整体性、系统性的理念与中医药“整体观念”、“辨证论治”的特点相一致，与中药“多成分、多靶点、多通路”的协同特征相契合。近年来，网络药理学技术越来越多地被应用于中药治疗COPD药效物质基础与作用机制等方面的研究，揭示了中药在改善炎症反应、氧化应激、蛋白酶/抗蛋白酶失衡、细胞凋亡等方面具有重要意义。但目前的研究仍处于起步阶段，在研究的可靠性、规范性及可验证性等方面存在一些不足。因此，对近年来网络药理学在中药治疗COPD作用机制的研究及其存在的问题进行综述，以期为作用机制的进一步研究提供参考。     

Progress in the design and quality control of placeboes for clinical trials of traditional Chinese medicine

In recent years, new preparations of traditional Chinese medicines (TCMs) have been developed, increasing the need for their clinical trials. Using placeboes rather than control drugs is increasingly popular in clinical trials of TCMs, as the therapeutic effects of the tested TCMs can be more properly judged. The basic attributes of TCM placeboes include similarity, safety, applicability and controllability. In particular, it is necessary to have similarities in appearance, color, smell and taste between the tested TCMs and placeboes. This is quite difficult for some TCMs due to their distinctive smell and taste. On the other hand, according to the TCM theory on homology of medicine and food, many foods also have certain bioactivities, potentially further complicating the selection of materials for TCM placeboes. In this review, firstly, studies on the special smell and taste of TCMs were introduced. Then, the preparation quality evaluation processes for TCM placeboes were summarized and discussed, based on the relevant literature published in recent years and the research results from our own lab. This review will facilitate the further research and development of TCM placeboes.     

中医药防治哮喘与Th1/Th2的平衡调节

支气管哮喘(简称哮喘)属世界多发病,疑难病,其发病机制目前尚不十分明确。因此,对于哮喘的防治存在一定的困难。当今的研究表明:Th1/Th2的失衡与哮喘的发病有着密切的关系,但是西医对于这一失衡问题缺乏有效的解决方法,中医药运用多途径、多环节、多靶点的治疗特点能有效解决这一问题。回顾中医药防治哮喘的相关研究,结合中医理论与西医发病机理,探讨中医药防治哮喘与Th1/Th2的平衡调节关系,以期为哮喘的防治开辟新思路与方法。     

纳米药物载体在中药制剂研发中的应用

纳米药物载体通常由天然或合成高分子材料制成，大小在10～1 000 nm ，因其具有靶向性、缓释性、载体材料可生物相容和降解等显著优点，已在药物制剂研发中得到广泛应用。近年来，中药纳米制剂发展迅速，作者通过查阅国内外文献，重点围绕毫微粒、脂质纳米粒、纳米乳、纳米胶束、纳米脂质体等几种典型的纳米载体的特性、制备及其在中药制剂研发中的应用进行综述。     

Syndrome differentiation in modern research of traditional Chinese medicine

Syndrome differentiation (Bian Zheng) in traditional Chinese medicine (TCM) is the comprehensive analysis of clinical information gained by the four main diagnostic TCM procedures: observation, listening, questioning, and pulse analysis, and it is used to guide the choice of treatment either by acupuncture and/or TCM herbal formulae, that is, Fufang. TCM syndrome differentiation can be used for further stratification of the patients' conditions with certain disease, identified by orthodox medical diagnosis, which could help the improvement of efficacy of the selected intervention. In modern TCM research it is possible to integrate syndrome differentiation with orthodox medical diagnosis leading to new scientific findings in overall medical diagnosis and treatment. In this review, the focus is to screen published evidence on the role of syndrome differentiation in modern TCM research with particular emphasis on basic and clinical research as well as, pharmacological evaluation of TCM herbal formulary for drug discovery.     

中药注射剂上市后整体评价的思路与关键

中药注射剂作为中药现代化的重要代表,已成为中医药产业不可或缺的一部分。该文从当前中药注射剂市场核心竞争力不足、研发生产水平不高、药品质量与安全性差等制约产业发展的瓶颈问题出发,指出需要对上市后中药注射剂进行整体性再评价,乃至二次开发。当前形势下,以具有良好临床基础、市场基础和研究基础的中药注射剂大品种为培育与评价主体,是集中力量实现产业创新发展的重要途径。与口服中成药不同,中药注射剂大品种培育需要更高的技术支撑、质量标准与更及时有效的临床信息反馈,因此需要探索构建适合中药注射剂的上市后整体评价研究体系。该文分别从评价方法的优化、医研企协同创新平台的搭建、整体评价研究体系的形成3个层次探讨了中药注射剂上市后整体评价研究体系的构建思路和关键,提出从机制规律基础研究、临床效果评价验证、文献信息积累挖掘、资源可持续性培育以及市场和产业化操作5个方面,实现"五位一体"共同服务于提高中药注射剂有效性、安全性、经济性及适用性的最终目标。     

关于中医临床疗效评价的若干思考

中医临床疗效评价研究是中医药研究领域内热点及难点问题,但是当前相关研究的整体水平还有待提高,在中医临床疗效评议研究领域内还存在着不少学术争议。笔者认为在开展中医临床疗效评价研究之前,要对其核心问题进行梳理,主要包括中医临床疗效的概念及其评价。近年来,已有国内学者围绕这些问题开展了一系列研究,并取得相应成绩,对这些问题的思考与回答将为解决中医临床疗效评价问题提供重要的支撑作用。     

现实性文献综述法及其在中医药领域研究中的应用

现实性文献综述法,也称为现实性文献整合法,是一种明确的、由理论驱动的证据综合方法,旨在解开复杂干预在特定环境下,如何工作(或失败的原因)机制的研究方法,具有解释性而非判断性。现实性文献综述法最初用来研究复杂社会干预,目前主要集中在卫生政策及医学领域。该方法根植于社会学,心理学,经济学和评估等领域的哲学和应用,是一种综合医疗保健证据的方法。而其与以中国古代哲学思想为思维架构,根据患者及环境整体辨证施治的具有人文与医学科学双重属性的中医药研究不谋而合。因而,可以考虑在中医药研究中应用实践,从而助力于中医药研究的发展,为中医药研究带来新的可能。现详细介绍现实性综述法的定义及发展过程,比较现实性综述法与系统综述法的区别,并就其具体实施步骤进行了研究及梳理,以便于应用和实践。最后,讨论其在中医药领域研究中应用的可行性以及需要注意的问题。     

中医药伦理审查的特色与对策探讨

中医药是我国医药宝库中的重要组成部分,在世界范围内产生越来越深刻的影响。目前,涉及中医药的临床研究越来越多。任何涉及人的医学研究都不可避免地会给参加研究的受试者带来风险。因此,伦理委员会对中医药相关项目的审查和监督就显得尤为重要。本文简要回顾了中医药伦理审查的建设历程。中医药伦理审查具有其自身特色的,这其中包括中医理论,中草药复方制剂等药物疗法,针灸、拔罐、推拿等非药物疗法等干预方式,以及试验设计、疗效评价、风险与受益等中医药临床研究中的实际问题。针对中医药研究的自身特色,本文提出落实并完善伦理审查制度和程序、提升委员审查能力、优化日常工作流程、提高主要研究者的伦理意识、运用外部认证估推动伦理工作发展等几点对策,不断提升中医药伦理审查的水平,完善受试者保护体系。     

计算机虚拟筛选技术在中药毒性研究中的探索与思考

近年来,中药安全性问题逐渐成为社会关注的热点,尤其是中药毒性研究更是中药研究的重点。因此,寻找高效的技术辅助中药毒性研究尤为关键。计算机虚拟筛选技术具有高效、便捷等优点,经过多年的发展,其技术理论已经趋于成熟,且在多个领域已被成功应用。通过对分子对接、机器学习、毒效团和分子相似性方法 4种主要的计算机虚拟筛选技术进行综述,并分析它们在中药毒性研究领域的应用和前景,为从事中药毒性研究的科研人员提供参考。     

酒精性肝纤维化中医证候研究评述

酒精性肝纤维化是目前研究的热点,中医治疗存在一定的优势。中医虽然对酒精性肝纤维化病名、病机及治疗进行了研究,但是至今仍然不够深入。本文从酒精性肝纤维化证候的文献回顾、证素研究、临床证候分布、实验室指标方面对证候研究现状进行了评述。认为对酒精性肝纤维化的病机和症状特点认识不同,造成证型判定不同或者证候命名不同,主要证型间的程度分级以及证候减轻、缓解或演变与病变的关系不明确,没有与病相结合形成合理的证型。酒精性肝纤维化证候研究已取得了较大的进展,但仍存在一些值得深入研讨的问题。     

Application of proteomics to determine the mechanism of action of traditional Chinese medicine remedies

Ethnopharmacological relevance

The rationale for using traditional Chinese medicine (TCM) is based on the experience that has been gained from its wide use over thousands of years. However, the mechanisms of action of many TCM are still unclear. Proteomics, which mainly characterizes protein functions, protein–protein interactions, and protein modification in tissues or animals, can be used to investigate signaling pathway perturbations in cells or the whole body. Proteomics has improved the discovery process of effective TCM compounds, and has helped to elucidate their possible mechanisms of action. Therefore, a systematic review of the application of proteomics on TCM research is of great importance and necessity. This review strives to describe the literature on the application of proteomics to elucidate the mechanism of action of TCM on various diseases, and provide the essential discussion on the further utilization of proteomics data to accelerate TCM research.

Materials and methods

Literature survey was performed via electronic search on Pubmed with keywords ‘Proteomics’ and ‘Traditional Chinese Medicine’. The papers written in English were acquired and analyzed in this review.

Results

This review mainly summarizes the application of proteomics to investigate TCM remedies for neuronal disease, cancer, cardiovascular disease, diabetes, and immunology-related disease.

Conclusions

Researchers have applied proteomics to study the mechanism of action of TCM and made substantial progresses. Further studies are required to determine the protein targets of the active compounds, analyze the mechanism of actions in patients, compare the clinical effects with western medicine.