Biological network-based exploration of the principles of traditional Chinese medicine

The clinical application of traditional Chinese medicine (TCM) relies on herbal formulas as the main form of prescription. The holistic effect of TCM treatment is a significant advantage in treating complex diseases, but also makes comprehension of the scientific principles of TCM challenging. There is an urgent need to establish new theories and methods in line with the holistic characteristics of TCM to address the needs of research regarding the complex relationship between the chemical constituents of TCM formulas and biological systems. The biological basis of TCM theory and the mechanism of action of TCM formula are not well understood. For a long time, there was a lack of holistic research methods and theories in TCM. The development of TCM has been severely hampered by these factors. Recently, emerging disciplines such as informatics and systems biology have made significant progress. Conducting intersecting research between TCM and cutting-edge science and technology, such as artificial intelligence, big data, and informatics, based on biological network, is becoming increasingly important. Multidisciplinary cross-research has become an important way to explore the scientific principles of TCM. Biological network-based "network target" theory breaks through the gap between macro- and micro-intrinsic correlation analysis, achieving organic integration of reductionism and holism. This brings new possibilities to explore the principles of TCM from a holistic perspective and bridge modern medicine with TCM. "Cold" and "Hot" are the core diagnostic and therapeutic concepts of TCM, and "treating pre-disease" is a distinctive theory thereof. The scientific principles of these TCM theories need to be explored by modern science and technology. Recently, biological network-based techniques, such as graphical neural networks, have been applied to the elucidation of the biological basis of TCM syndrome, the analysis of the mechanism of action of TCM formulas, and the discovery of biomarkers. Precision prevention and treatment in TCM and precision research and development of TCM formulae have made remarkable progress due to the further elucidation of the principles of TCM. We aimed to review the theory and methodology of TCM research based on biological network, and its application in the interpretation of the scientific basis of disease-syndrome combination of the distinctive TCM theories such as "Cold/Hot" and "treating pre-disease". The elucidation of TCM principles from a biological network perspective requires high-quality TCM big data. In the future, research on the principles of TCM based on the biological network should first obtain high-quality TCM big data, combined with constant development and updating of algorithms to build more accurate prediction models. The established methods should be tested in experiments and clinics, enabling the development of artificial intelligence and big data to truly enhance the scientific and translational research of TCM. Based on the research progress from Shao Li's lab, this review provides an up-to-date overview of the use modern science and technology to interpret the principles of TCM and promote the modernization of TCM from the perspective of the biological network.