Chinese Medicine formulae (CMFs), also known as Chinese herbal formulae, are complex mixtures of medicinals used to treat various diseases based on the holistic theory of Chinese Medicine, which emphasises the balance and interaction between different components of the human body and their environment. These formulae are designed to treat the body as a whole, addressing multiple symptoms and underlying causes simultaneously. They often contain multiple medicinals that work synergistically to enhance therapeutic effects and reduce side effects. There were approximately 1,600 research outputs interested in formulae ^[1] between 2014 and 2023, and research on CMFs has been growing across various scientific fields, including pharmacology, bioinformatics, and systems biology. With a long history of clinical use, modern research aims to validate and optimise these traditional practices using scientific methods.

CMFs approach the treatment of various diseases from a holistic perspective, and research on them spans a wide range of medical conditions. Researchers are dedicated to elucidating the key bioactive substances and functional mechanisms of CMFs, promoting their global acceptance.

For gynaecological disorders, CMFs address conditions like endometriosis, infertility, dysmenorrhea, polycystic ovary syndrome (PCOS), and vaginitis.^[2] Metabolic and endocrine disorders, such as hyperlipidaemia and type 2 diabetes,^[3] are treated to enhance excretory functions and improve cardiovascular health. Chronic inflammatory and autoimmune diseases, including atopic dermatitis,^[4] are managed with bioactive ingredients that regulate immune responses. Cardiovascular and cerebrovascular diseases, like ischemic heart disease, myocardial infarction, and stroke, benefit from medicinals promoting blood circulation and tonifying Qi, like Processed Licorice Decoction and danshen.^[5] Chronic liver diseases, including hepatitis and cirrhosis, are managed with medicinals like danshen.^[6] CMFs also show efficacy in treating infectious diseases like COVID-19, SARS, and H7N9 flu with formulae such as Lianhua Qingwen Capsule.^[7]

Research on CMFs adopts an integrative and holistic approach, beginning with a comprehensive perspective, focusing on specific pathways, and then returning to the overall picture. This method links bioactive compounds to clinical outcomes through bioinformatic analysis, indicating that the synergistic effects of multiple components and targets contribute to CMFs’ efficacy. The holistic nature of this research considers the interconnectedness of physiological systems, which is particularly relevant for treating complex diseases like COVID-19, where a multi-faceted approach is essential.

In a milestone research study^[8] on Chinese Medicine, Chen and his team suggest that dissecting the modes of action of clinically effective formulae at the molecular, cellular, and organism levels could be a promising strategy for exploring the value of traditional medicine. To investigate the mechanisms of a traditional Chinese Medicine product, Chen and colleagues analysed the active ingredients of the Realgar–Indigo naturalis formula. At the cellular level, the combination of active ingredients was found to be synergistic, intensifying the ubiquitylation and degradation of the promyelocytic leukaemia (PML)-retinoic acid receptor-α oncoprotein. This led to stronger reprogramming of myeloid differentiation regulators and enhanced cell-cycle arrest. In a murine model of acute PML, the combined active ingredients significantly prolonged the lifespan of the mice. One crucial aspect of this research is its molecular-level insights, which reveal the biochemical pathways through which CMFs exert their effects. This mechanistic understanding is essential for validating the use of traditional medicine in modern clinical settings.

The study of Huashi Baidu Decoction exemplifies the complexity and potential of the research related to CMFs. Out of more than three hundred compounds characterised from Huashi Baidu Decoction, four compounds demonstrated both anti-SARS-CoV-2 and anti-inflammatory activities, underscoring the potential of CMFs to address multiple aspects of disease pathology simultaneously. This dual action is particularly relevant in the context of COVID-19, where both viral replication and the inflammatory response play critical roles in disease progression. The discovery of metabolites in plasma adds another layer of complexity to the understanding of Huashi Baidu Decoction’s effects. These metabolites could be key contributors to the decoction’s overall therapeutic profile, influencing both efficacy and safety. The involvement of pathways such as the immune-inflammatory system, angiogenesis, platelet activation, and energy metabolism suggests that Huashi Baidu Decoction addresses both the symptoms and underlying causes of COVID-19 in a holistic manner.

The study of CMFs typically begins with clinical validation, followed by fundamental research to elucidate the underlying mechanisms. For instance, a large-scale double-blinded randomised controlled trial^[9] involving 3,110 patients from 133 hospitals demonstrated that Qiliqiangxin Capsule effectively reduced hospitalisations and cardiovascular deaths in patients with heart failure and reduced ejection fraction, establishing its clinical efficacy and safety. Similarly, Jinlida Granule has been clinically proven to lower the risk of progression from impaired glucose tolerance to diabetes by addressing multiple metabolic abnormalities.^[10] These clinical validations are crucial as they provide robust evidence supporting the effectiveness and safety of CMFs in real-world settings.

Following these clinical successes, basic research is undertaken to explore the biochemical and physiological mechanisms at play. This approach helps to reveal the pathways through which these CMFs exert their therapeutic effects. For example, Shexiang Baoxin Pill has been shown to improve cardiac energy metabolism and vascular function by regulating purine metabolism and enhancing beneficial gut bacteria, particularly Lactobacillus.^[11] This dual action not only decreases inosine production and ameliorates purine metabolic disorders but also inhibits genes involved in thrombosis, inflammation, and platelet function. Understanding these mechanisms provides scientific validation for the observed clinical benefits and opens up new avenues for developing innovative therapeutic strategies inspired by traditional medicine. This integrative approach, combining clinical trials with basic research, ensures a comprehensive understanding of CMFs and their potential applications in modern healthcare.

The use of modern medical technologies, such as omics technologies and bioinformatics, has significantly advanced the research of CMFs, offering comprehensive insights into their mechanisms and therapeutic effects. Omics technologies, including transcriptomics, proteomics, and metabolomics, enable high-throughput analysis that is crucial for understanding the multi-component and multi-target nature of Chinese Medicinals. By integrating multiple omics approaches, researchers can align with the holistic concept of Chinese Medicine, gaining a more comprehensive understanding of the interactions between various components and their collective therapeutic effects. These technologies help elucidate the mechanisms of action of CMFs by providing multilayered data that characterise the overall therapeutic relationships.

Bioinformatics plays a crucial role in integrating and analysing the vast amounts of data generated by omics technologies, essential for understanding the complex biological functionalities and therapeutic mechanisms of Chinese Medicinals. Tools such as network pharmacology and systems biology facilitate mapping out the interactions between Chinese Medicinal components and their biological targets, offering deeper insights into their therapeutic effects. The combination of omics technologies and bioinformatics supports quality control, drug discovery, and personalised medicine, ensuring the consistency, efficacy, and safety of Chinese Medicine products. Despite challenges like data complexity and the need for integration with modern medicine, these advancements have revolutionised the understanding and application of CMFs, paving the way for their modernisation and global integration into healthcare systems.

[1] Research outputs mentioned “formulas” or “formulae” in title, abstract or keywords.

[2] Hu, C., et al. “Guizhi Fuling Capsule, an Ancient Chinese Formula, Attenuates Endometriosis in Rats via Induction of Apoptosis.” Climacteric, vol. 17, no. 4, Taylor & Francis, Feb. 2014, pp. 410–16, https://doi.org/10.3109/13697137.2013.876618.

[3] Cai, Shengyu, et al. “Effect of Mulberry Leaf (Folium Mori) on Insulin Resistance via IRS-1/PI3K/Glut-4 Signalling Pathway in Type 2 Diabetes Mellitus Rats.” Pharmaceutical Biology, vol. 54, no. 11, May 2016, pp. 2685–91, https://doi.org/10.1080/13880209.2016.1178779.

[4] Yan, Fenggen, et al. “The Formulae and Biologically Active Ingredients of Chinese Herbal Medicines for the Treatment of Atopic Dermatitis.” Biomedicine & Pharmacotherapy, vol. 127, July 2020, p. 110142, https://doi.org/10.1016/j.biopha.2020.110142.

[5] Wang, Lung-Shuo, et al. “Clinical Patterns of Traditional Chinese Medicine for Ischemic Heart Disease Treatment: A Population-Based Cohort Study.” Medicina, vol. 58, no. 7, July 2022, p. 879, https://doi.org/10.3390/medicina58070879.

[6] Xu, Feipeng, et al. “Recent Progress on the Application of Compound Formulas of Traditional Chinese Medicine in Clinical Trials and Basic Research in Vivo for Chronic Liver Disease.” Journal of Ethnopharmacology, vol. 321, Elsevier BV, Dec. 2023, pp. 117514–14, https://doi.org/10.1016/j.jep.2023.117514.

[7] Li, Runfeng, et al. “Lianhuaqingwen Exerts Anti-Viral and Anti-Inflammatory Activity against Novel Coronavirus (SARS-CoV-2).” Pharmacological Research, vol. 156, June 2020, p. 104761, https://doi.org/10.1016/j.phrs.2020.104761.

[8] Wang, Lan, et al. “Dissection of Mechanisms of Chinese Medicinal Formula Realgar-Indigo Naturalis as an Effective Treatment for Promyelocytic Leukemia.” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 12, Mar. 2008, pp. 4826–31, https://doi.org/10.1073/pnas.0712365105. Accessed 5 Mar. 2021.

[9] Cheang, Iokfai, et al. “The Traditional Chinese Medicine Qiliqiangxin in Heart Failure with Reduced Ejection Fraction: A Randomized, Double-Blind, Placebo-Controlled Trial.” Nature Medicine, vol. 30, no. 8, Nature Portfolio, Aug. 2024, pp. 2295–302, https://doi.org/10.1038/s41591-024-03169-2.

[10] Ji, Hangyu, et al. “Jinlida for Diabetes Prevention in Impaired Glucose Tolerance and Multiple Metabolic Abnormalities.” JAMA Internal Medicine, vol. 184, no. 7, American Medical Association, June 2024, pp. 727–27, https://doi.org/10.1001/jamainternmed.2024.1190.

[11] Wu, Gaosong, et al. “Shexiang Baoxin Pill Enriches Lactobacillus to Regulate Purine Metabolism in Patients with Stable Coronary Artery Disease.” Phytomedicine, vol. 130, Elsevier BV, May 2024, pp. 155727–27, https://doi.org/10.1016/j.phymed.2024.155727.