Network Pharmacology-based Approaches Capture Essence of Chinese Herbal Medicines

Traditional Chinese Medicine (TCM), a crucial component of the current medical system, has been extensively used in clinical practice due to its valuable therapeutic efficacy, and its potentials as an important source of new pharmacophores. TCM is characterized by holistic theory, which emphasizes maintaining the balance of the patient’s whole body using herbal formulae (fangji in Chinese) composed of mixtures of herbs with multiple bioactive ingredients. Because of the complex nature of these formulae, it is necessary to develop systematic methods to identify their bioactive ingredients and to clarify their mechanisms of action. With the rapid progress in bioinformatics, systems biology, and polypharmacology, “network pharmacology”, which shifts the “one target, one drug” paradigm to the “network target, multi-component” strategy, has attracted the attention because it can not only reveal the underlying complex interactions between a herbal formula and cellular proteins but detect the influence of their interactions on the function and behavior of the system. Growing evidence shows that the network pharmacology strategy can be a powerful approach to modern research on TCM. The present paper focuses on the basis of network pharmacology and the recent progress in its methodology, illustrates its utility in screening bioactive ingredients and elucidating the mechanisms of action of TCM herbal formulae, analyzes its limitations and problems, and discusses its development direction and application prospects.     

Development and Application of Network Toxicology in Safety Research of Chinese Materia Medica

Network toxicology that is an important branch of the network pharmacology emerges on the basis of network biology. It refers to study on the toxicological features of a constructed network model which is used to analyze toxic substances and their interaction and regulation in biological systems, particularly investigate the toxic effects of drugs and/or compatibility of medicines on body, and clarify the mechanism of toxicity. Network toxicology currently develops rapidly in safety prediction of Chinese materia medica(CMM). The application of network toxicology to safety and toxicology study on CMM is extremely beneficial to identify the toxic components and potential incompatibility of CMM. Since CMM is a complex system with multi-components, multi-targets, and multi-interactions, the network toxicology in safety prediction of CMM faces three great challenges, including integration studies of bioinformatics, innovation of methods, and tools and risk assessment in future development of the network toxicology in CMM research. In this paper, relevant database, approaches and tools that network toxicology utilized in the safety study of CMM were carefully reviewed. Based on the progress made, the scientific development and modernization of CMM will be greatly enhanced.     

Network pharmacology in quality control of traditional Chinese medicines

Traditional Chinese medicine (TCM) has been widely used to treat and prevent diseases for thousands of years in China and is generally recognized for its unique holistic view and remarkable therapeutic effect on complex diseases. The worldwide interest to TCM has been increasing in recent years, especially since TCM has shown inspiring efficacy in the treatment of COVID-19. These attentions include both recognition of the important role of TCM and doubts about its efficacy and safety. At present, the internationalization and modernization of TCM are facing many challenges, such as unclear biological mechanism of herbs and formulae, and the difficulty of ensuring the quality and safety of TCM. Given the multi-component and multi-target characteristics of TCM, how to systematically describe the interaction between TCM and complex diseases, evaluate the efficacy and toxicity of TCM and carry out quality control has become the focus and difficulty of research. Network pharmacology, as a systematic and holistic medical research paradigm, can help to systematically reveal the biological basis of TCM, and has been widely used in the research of TCM bioactive ingredients, syndromes, formulae, and other topics. The concept of "network target" based on TCM research (Li et al., 2011) has been used to explore new methods and applications since its inception, leading to a new discipline of TCM network pharmacology (Li and Zhang, 2013). On the one hand, TCM network pharmacology research shows the tendency of combining computational, experimental and clinical approaches (Wang et al., 2021), and the research paradigm is improving continuously. On the other hand, the application of network pharmacology is expanding to a variety of aspects in TCM research. It has been applied in fields such as exploring the biological basic of disease and syndrome, uncovering the mechanism of TCM formulae, identifying toxic components and quality markers (Q-Marker) of traditional Chinese medicine and so on. The concept of Q-Marker which was proposed by Prof. Liu to standardize the quality research of TCM has established an effective research framework for the quality control of traditional Chinese medicine (Liu et al., 2017). Since it was proposed, Q-Marker has been utilized by researchers to analyze many TCM herbs and formulae, making an important contribution to the TCM quality control system. A previous research strategy of predicting and determining Q-Marker based on network pharmacology method (Wang et al, 2019) shows the potential of network pharmacology combined with Q-Marker in the application of quality control of TCM. The effectiveness and safety of TCM are taken into consideration when determining Q-Marker. There have been many successful application cases of network pharmacology in studying the effective ingredients and mechanism of TCM, and network pharmacology is also being used more and more frequently in the study of TCM toxicity. This issue will publish a research paper titled “Integrating systematic pharmacology-based strategy and experimental validation to explore mechanism of Tripterygium glycoside on cholangiocyte-related liver injury” on the use of network pharmacology to explore the toxic components of TCM and their underlying mechanisms. Tripterygium glycoside (TG) extracted from Tripterygium wilfordii have been used in clinical treatment of rheumatoid arthritis and other diseases, and there are several new indications under study. However, hepatotoxicity, the main adverse effect of TG in clinical practice, is an urgent problem to be solved. By combining network pharmacological analysis with in vivo and in vitro experimental verification, the authors discovered that triptolide, the primary toxic component of TG, could inhibit proliferation and promoted apoptosis of cholangiocytes by inhibiting the phosphorylation of ERK1/2 and AKT and activating Bax and cleaved-Caspase 3 signaling. This study is a typical example of using network pharmacology to predict the toxic components and mechanisms of TCM. At the same time, it also shows that network pharmacology can be combined with Q-Marker strategy to identify the toxicity Q-Marker of TCM, and aids in the quality control and standardization of traditional Chinese medicine. As a discipline that has been developed for a short period of time, there are still many challenges in the theory, methodology and application of network pharmacology. The quality control research of TCM using network pharmacology also needs more investigation and exploration. The publication of Network Pharmacology Evaluation Method Guidance in 2021 has positive implications for the standardization of network pharmacology research and promotes the healthy development of the discipline (Li, 2021). However, as the fields of network pharmacology research continues to expand, the guidance cannot cover all kinds of research and need to be updated and revised in time. With the combination with new technologies such as artificial intelligence high-throughput technologies, network pharmacology will undoubtedly develop at a high speed. We look forward to a wider application of network pharmacology in TCM research, which will provide new scientific evidence for deciphering the mysteries of TCM and thus promote the inheritance, innovation and development of TCM.     

Prediction of quality markers of traditional Chinese medicines based on network pharmacology

Network pharmacology is a powerful tool to reflect the pharmacologically active effects, mechanism of action and toxic activity of traditional Chinese medicines (TCMs). The ingredients of TCMs, associated with quality control of TCM products, are those fundamental chemicals that exhibit biological activities. A great amount of effort has been made by scientists in that field in order to improve the quality of TCMs, though the approaches to determine their quality and the TCM theory and compatibility rules remain ambiguous. Now some methods and technologies must be applied to predict and explore the quality marker (Q-marker) for quality control, as well as to clarify the factors affecting the quality of TCM, which may give new insight into rational ground of establishment of appropriate quality control and assessment system. In this review paper, authors focus on the prediction of quality markers of TCMs by network pharmacology based on three aspects: (1) from network medicine to network pharmacology, (2) complex network system of traditional Chinese medicine, and (3) predicting TCM quality markers based on network pharmacology. Authors proposed the research pattern on network pharmacology based on biological and medical networks, and further TCM network pharmacology based on substantial basis of TCM formulae, and the idea of “effect-ingredient-target-fingerprint” to predict and recognize the TCM Q-marker was the ultimate goal. In addition, authors yet noted how to make full use of the advantages of network toxicology to provide new ideas for the toxicity study of complex TCM systems and the prediction of TCM toxicity markers.     

Network Pharmacology for Traditional Chinese Medicine Research: Methodologies and Applications

The inception of network pharmacology comes from the advance in "multi-target, multi-drug" paradigm and opens up a new field for pharmaceutical science. Traditional Chinese medicine(TCM) is well-known for its use of medicinal herb combinations to treat the functional disorders induced by diseases through a holistic view, which naturally followed the principal of network pharmacology. In this review, the methodologies of network pharmacology in TCM studies were summarized. Specifically, the methodologies for network construction and network analysis were discussed in detail by following several TCM study cases. The perspectives for TCM network pharmacology were also provided.     

TCM-based new drug discovery and development in China

Over the past 30 years, China has significantly improved the drug development environment by establishing a se- ries of policies for the regulation of new drug approval. The regulatory system for new drug evaluation and registration in China was gradually developed in accordance with international standards. The approval and registration of TCM in China became as strict as those of chemical drugs and biological products. In this review, TCM-based new drug discovery and development are in- troduced according to the TCM classification of nine categories.     

Integration strategy of network pharmacology in Traditional Chinese Medicine: a narrative review

Traditional Chinese Medicine(TCM) has been extensively used as a mainstay for treating various pathologies. Combing the pharmacology and systems biology approaches, the network pharmacology(NP) approach was developed to predict the probable mechanism underlying the therapeutic effect of TCM. However, approaches solely based on NP cannot effectively elucidate the curative mechanism in a holistic and reliable manner due to limitations in NP-based methods and complexity of TCM components. Thus, int...     

Aims & Scope

正Aim:WJTCM is intended to publish the recent research progress in clinical efficacy and action mechanism of traditional Chinese Medicine,Chinese materia medica,acupuncture and moxibustion so as to provide new insight and research methodologies for approaching complex diseases with the art and science of traditional Chinese medicine.WJTCM has four columns listed as the following:Modern Research on Chinese Materia Medica:including theories of TCM processing,theories of drug property and compatibility,TCM quality control,TCM toxicology,TCM pharmacology,pharmacokinetics,systems biology and mechanism of actions,     

Progress of Studies on Traditional Chinese Medicine Based on Complex Network Analysis

Traditional Chinese medicine (TCM) is a distinct medical system that deals with the life–health–disease–environment relationship using holistic, dynamic, and dialectical thinking. However, reductionism has often restricted the conventional studies on TCM, and these studies did not investigate the central concepts of TCM theory about the multiple relationships among life, health, disease, and environment. Complex network analysis describes a wide variety of complex systems in the real world, and it has the potential to bridge the gap between TCM and modern science owing to the holism of TCM theory. This article summarizes the current research involving TCM network analysis and highlights the computational tools and analysis methods involved in this research. Finally, to inspire a new approach, the article discussed the potential problems underlying the application of TCM network analysis     

Integrated Systems Biology and Chemical Biology Approach to Exploring Mechanisms of Traditional Chinese Medicines

After thousands of years of development, traditional Chinese medicines (TCMs) have evolved into a complete scientific system characterized by multiple components, targets, and pathways, which mediates numerous pharmacological activities and efficacies. The development of “-omics” technology, including systems biology and network pharmacology, has enabled the illustration of TCMs from a more systematic view. Although the network adequately reflects the overall philosophy of TCMs, its complexity hinders the relevant research to a hover. In addition, the strategies involved appear to be in contrast to the original concise and efficacious disease therapy oriented focus on classic Chinese material medica (CMM). Based on the established holistic view and reductionism, in this review, we discuss an integrated systems biology and chemical biology research approach that will facilitate and accelerate the understanding of the mechanisms of TCMs. Furthermore, we are optimistic that it will elucidate the associated interactions between active natural products and their targets, and ultimately improve the strategies for complex disease therapies.     

基于系统生物学与网络生物学的现代中药复方研究体系

建立行之有效的现代中药复方研究体系,是中医药现代化进程中亟待解决的关键问题之一。本文遵循系统论和还原论相结合、宏观与微观研究相结合、体内研究和体外研究相结合的原则,以系统生物学与网络生物学作为主要技术支撑,尝试提出包括化学物质基础研究、现代药理学研究、系统生物学和网络生物学研究在内的现代中药复方研究体系,并结合中药复方的具体研究实例,对该研究体系指导下的中药复方现代化研究进行了初步探讨。本文提出的复方研究体系为中药复方的现代研究提供了方法论,将有助于系统、深刻地揭示中药复方的科学内涵,指导中药复方新药研发,更好地传承和发展中医药理论。     

系统生物学意义下的中药研发与药性理论

基于系统生物学的药物研发过程与中医诊疗过程的一致性，中医药与系统生物学存在相互借鉴、共同发展的关系。作者利用中医药的思想和系统生物学的技术手段，研究中药药性的系统学意义，建立基于药性的中药药效评价方法，对于中药新药研发和中医药学在医药学转型过程中发挥主导作用具有重要意义，也是中医药发展的战略问题。     

中医药网络药理学:《指南》引领下的新时代发展

中医药凭借整体观和两千多年来临床使用天然药物的实践经验,在疾病的预防和治疗中有独特优势.中医药诊疗思想和丰富临床经验中的"整体"特色孕育了以"网络"和"系统"为特色的新一代研究模式.该模式在生物医学大数据和人工智能时代得到了快速发展,其中有代表性的研究领域——"网络药理学"为人工智能与中西医学交叉研究、分析海量生物医学...     

基于代谢网络变化的中药整体效应评价方法研究

由于中医的“整体观”和中药复方的复杂非线形特征，采用常规药理指标对中药复方的效应进行评价存在着局限性，而现代医学越来越多地采用系统生物学方法对疾病和药物效应进行研究．使得两个医学体系在整体观和方法学上逐渐走向沟通、互补和融合，为中药复方整体效应评价方法的创新提供了契机。通过研究本文提出了采用系统生物学的策略和方法，基于疾病和药物干预下的系统代谢网络的整体性和动态性的变化评价中药整体效应，从而揭示中医“证”的内涵，解释中药复方对疾病的治疗作用，以及指导中药的安全用药。     

基于系统药理学的现代中药研究体系

由于系统生物学的高速发展,以及系统生物学对现代药理学领域的深刻影响,近年来正在形成一个新兴的、跨学科分支,即系统药理学（Systems Pharmacology）。然而系统药理学无论在理论和方法上均不成熟。尤其是,如何将系统药理学的思想和理论用于中药研究尚缺乏探索性工作。本文将综述当前系统药理学的最新进展,同时结合研究者的实践,重点介绍如何将药效学、药动学以及网络、组学以及系统分析综合起来,形成一个统一的完整的、可供开展中药药理学、药效学的预测和验证研究的系统模型。从而为从系统水平研究和分析中药和机体的相互作用,以及新药开发、靶点发现、新的治疗策略等提供新的研究方法。文章最后介绍了研究者最新开发的中药系统药理学数据库和分析平台软件。     

网络靶标:中药方剂网络药理学研究的一个切入点

目前中药研究的一个重点和难点问题是理解中药方剂复杂化学体系与病证复杂生物系统的相互作用.作者通过多年研究,从网络药理学、系统生物学角度对该问题提出“网络靶标”这一新的概念与方法.网络靶标概念指的是将病证生物分子网络当作靶标,由此设计和预测最佳的药物干预方式.网络靶标方法旨在将病证、方药映射于生物分子网络,然后在网络上对病证与方药的关系进行机制性的计算、分析与预测,以期发现药效物质及其作用机制,阐释方剂配伍规律与方证关联,并进行组方用药的理性设计.该文概述作者课题组在网络靶标方法及其在中药方剂中的应用进展,希望能为中药方剂的网络药理学研究提供参考.     

系统生物学意义下的中药研发与药性理论

基于系统生物学的药物研发过程与中医诊疗过程的一致性,中医药与系统生物学存在相互借鉴、共同发展的关系。作者利用中医药的思想和系统生物学的技术手段,研究中药药性的系统学意义,建立基于药性的中药药效评价方法,对于中药新药研发和中医药学在医药学转型过程中发挥主导作用具有重要意义,也是中医药发展的战略问题。     

基于网络生物学方法的中药药理作用机制研究思考与探索

中药复方多成分、多靶点协同作用的药理作用机制研究是中药现代化和国际化的"瓶颈"之一。近年出现的网络生物学研究方法为中药复方药理作用机制系统研究提供重要而有效的新思路、新模式。本文介绍了网络生物学研究的数学基础、论述了网络生物学在中药药理作用机制研究中的可行性,并提出了网络生物学在中药药理作用机制方面的研究思路。网络生物学可望为中药药理作用机制研究奠定理论基础,指导中药复方药物的开发,更好地继承和发扬祖国中医药学理论。     

网络药理学指导下的中药有效成分发现策略

网络药理学是建立在疾病-基因-药物的多层次网络基础上,用于从整体上预测药物靶点、提高药物发现效率的新兴学科,其研究理念同中药发挥整体疗效的观点十分相似,使得越来越多的医药研究人员开始寻找中药与网络药理学的结合点,并出现了一系列研究疾病相关基因、预测靶点信息及中药活性成分的方法。本文对网络药理学研究的主要工具与数据库及其应用进行归类总结与介绍,并在此基础上,提出了应用网络药理学进行中药有效成分靶向分离的科学策略,以期提高中药有效成分发现的效率与速率。