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.