Symptom-Driven Drug Development: Bridging Traditional Chinese Medicine and Western Pharmacology Editorial: Traditional Clinical Symptoms and Signs: How Can They Be Used to Investigate Medications in the Context of Pharmacology?

Kuo Gao ¹ Michael Heinrich ² Hui Hui Zhao ^1* Xuezhong Zhou ^3* Shao Li ^4*

• ¹ School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
• ² School of Pharmacy, Faculty of Life Sciences, University College London, London, England, United Kingdom
• ³ School of Computer and Information Technology, Beijing Jiaotong University, Beijing, China
• ⁴ Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, Beijing Municipality, China

Modern drug development has traditionally focused on disease pathology, often neglecting the critical role of symptom management. However, symptoms are not merely indicators of disease; they are integral to the patient's experience and can provide unique insights into therapeutic interventions. In Traditional Chinese Medicine (TCM) , symptoms often serve as both diagnostic markers and disease names, bridging the gap between traditional and biomedical systems (Su et al., 2012). This connection suggests that if symptoms are associated with a disease and specific medicines exist for that condition, there may be a latent relationship between the symptoms and the medicines (Bhattacharjee et al., 2024). This relationship is particularly crucial for diseases that are difficult to diagnose or lack effective treatments, even when a diagnosis is clear. Symptom-based treatment aims not only to address the disease but also to improve the patient's quality of life (Jurgens et al., 2022). However, integrating traditional and biomedical approaches presents significant challenges, as local and traditional disease concepts must be understood within their cultural contexts, and direct correlations with biomedical models are often lacking.Contemporary pharmacology faces significant challenges in research and development, including high costs, lengthy development cycles, and high failure rates. However, medicines are ultimately meant for human, and their efficacy and effectiveness must be evaluated based on patient responses. Drug development targeting symptoms and signs arises from observations in the real clinical world, which often leads to higher success rates (Liu et al., 2023). Some specific treatments used in TCM, for example, have unique advantages in symptom treatment, with many potential natural medicines waiting to be developed. In particular, TCM practitioners currently prescribe medications based on clinical symptoms and signs rather than solely on diseases (Li et al., 2006). This results in different symptoms and treatments for the same disease due to individual constitution and condition (Sun et al., 2020). This truly embodies a patient-centered approach rather than a disease-centered one. It can be said that symptoms are the targets of TCM treatment. Other medical traditional offer similar opportunities, as exemplified in many studies (Geck et al., 2020).With advancements in information processing technology, pharmacological research based on symptoms and signs is once more gaining attention. The collection and processing of multi-source big data, including images, are gradually becoming possible, leading to the establishment of relevant databases (Wu et al., 2019). Drug development has brought new opportunities and is expected to open new research fields (Xu et al., 2016). This Research Topic explores how symptoms and signs facilitate the integration of TCM and biomedicine, featuring contributions from esteemed scholars and garnering positive attention from the academic community. A total of 58 manuscripts from 8 countries and regions were received, and after careful review by editors, reviewers and the Editor-in-Chief including a full assessment using Frontiers' AIRA (Artificial Intelligence Research Assistant), eleven papers, including ten original articles and one review, authored by 106 scholars were published.Personalization is a hallmark of many traditional medical systems including TCM or Korean medicine. Even when patients are prescribed the same herbal medicine, their responses can vary significantly due to individual symptom profiles, such as blood stasis, qi deficiency, qi stagnation, phlegm-dampness, yin deficiency, yang deficiency, and cold congealing. The mechanisms of action of these medicines can differ for the same disease depending on the specific symptoms presentation (Yang et al., 2022).Therefore,, both clinical practice and research should emphasize the integration of diseases and symptoms profiles, categorizing symptoms according to their associated diseases (Hansen et al., 2022).The pharmacology of TCM-based preparations is confronted with challenges and requirements as is the case in many other traditional medical systems. Many studies on the pharmacology of Chinese medicinal plants overlook specific symptoms, resulting in unstable outcomes. Randomized controlled trials (RCT) have important limitations; without appropriate classification under diseases, RCT may be futile (Zhu et al., 2024).TCM emphasizes personalized treatment, tailoring therapies to individual symptom profiles rather than adopting a one-size-fits-all approach. Pharmacological research must clearly define TCM disease classifications, as this is essential for ensuring stable efficacy in treatment (Gao et al., 2017) and a plausible link to a clinical outcome measures of pharmacological models is essential (see the journal's Four Pillars of Best Practice Section 1b -www.frontiersin.org/files/pdf/4_pillars_FULL_TEXT.pdf). Therefore, whether a specific disease can achieve therapeutic effects depends not only on chemical components but also on the individual's TCM classification, which is a key insight from this issue's theme. Of note, there are parallels with some newer and emerging biomedical approaches, where specific efficacy levels are linked to the characteristics of a study population (Snapinn and Jiang, 2007). Network analysis is an emerging field that utilizes systems biology and bioinformatics to study the complex interactions between medicines and biological systems (Lai et al., 2020) (Kong et al., 2024) (Liu et al., 2023) (Han et al., 2023) (Zhang et al., 2023).There are several direct associations among the components including TCM symptom-herb, TCM symptom-modern medicine (MM) symptom, MM symptom-disease, herbingredient, ingredient-target and target-disease (also referred to as gene-disease) associations, and other indirect associations for TCM symptom-ingredient, herb-target, ingredient-disease, and MM symptom-target relationships (Wu et al., 2019).Transcriptomics, the study of all RNA molecules in a biological system at a specific time and under certain conditions (Robinson et al., 2022), offers new perspectives in TCM research by uncovering the mechanisms of herbal treatments (Yang et al., 2022).Metabolomics, a systems biology approach, reveals the metabolic state of a biological system by analysing metabolites in biological samples (Ajoolabady et al., 2024) (Liu et al., 2025). In TCM research, animal and cell models are extensively used to evaluate the pharmacological effects and safety of Chinese medicines. These models allow researchers to explore the mechanisms of action of herbal treatments, providing scientific evidence for drug development (Yan et al., 2025).Zhachong Shisanwei Pills (ZSP), a highly esteemed Mongolian medicinal formulation, comprises thirteen traditional herbal ingredients and is used to ease tension in the tendons, enhance blood circulation, and impart a calming and tranquilizing effect on This Research Topic highlights the significance of symptom-oriented drug development, demonstrating how the integration of traditional and modern pharmacological approaches can lead to more effective and personalized treatments. By incorporating animal and cellular experiments, researchers can further explore the biological foundations of symptom-targeted therapies in traditional medical systems such as Kampo or TCM. Several studies demonstrated the potential of methodologies focused on understanding symptoms, while others have adopted a more traditional approach