Recent Progress Bridges Gap between Traditional Medical Knowledge and Modern Scientific Methodologies

A research team led by Associate Professor Yiwen Wang from the School of Pharmaceutical Science and Technology, Tianjin University, developed a novel screening strategy using a Drosophila (fruit fly) model to identify anti-nephrolithiasis compounds from herbal medicines. A pathological model of kidney stone formation was successfully established by inducing crystal deposits in the Malpighian tubules of fruit flies —organs functionally analogous to the human renal tubules— with sodium oxalate.

Their study titled "Streamlined strategy for discovering active compounds for nephrolithiasis treatment from herbal medicines using the fruit fly model" was recently published in the internationally renowned journal Journal of Ethnopharmacology. 

Kidney stones are a globally prevalent urinary system disorder with a rising incidence in recent years. Traditional Chinese Medicine (TCM) has shown unique advantages in the prevention and treatment of kidney stones due to its efficacy and low side effects. However, the complexity of TCM formulations poses major challenges in identifying bioactive ingredients and elucidating their mechanisms of action. Establishing an efficient and reliable research model is crucial to addressing these obstacles.

The strategy developed by the research team led by Associate Professor Yiwen Wang integrates multiple steps, including screening of TCM water extracts, solid-phase extraction, LC-MS/NMR-based compound identification, and multi-level biological validation, thereby constructing a complete and efficient pipeline for active compound discovery. Through this strategy, the team screened 15 candidate TCMs and identified three with significant anti-urolithic activity: Honghua (HH), Danshen (DS), and Huangqi (HQ). Their respective major active compounds were identified as Hydroxysafflor yellow A (HYA), Salvianic acid A (SAA), and Calycosin-7-O-β-D-glucoside (CG). Mechanistic studies showed that both HYA and SAA inhibit crystal deposition and alleviate oxidative stress, while CG additionally enhances diuresis, which aids in stone excretion. These therapeutic effects were further validated in a glyoxylate-induced mouse model of nephrolithiasis, confirming the cross-species efficacy of the identified compounds. Notably, the strong consistency between the mechanisms of action of water extracts and their purified constituents offers experimental evidence supporting the rational basis of traditional decoctions.

This study establishes a comprehensive research paradigm — “Drosophila screening – chemical analysis – mammalian validation” — and identifies three novel candidate compounds for nephrolithiasis treatment. It lays a solid material foundation for future drug development. By integrating the Drosophila model with chemical separation and identification techniques, this efficient strategy demonstrates the model’s value in discovering bioactive compounds from complex herbal mixtures and contributes to the modernization of TCM research.

The study also highlights several unique advantages of the Drosophila model: its suitability for high-throughput screening significantly shortens the drug discovery timeline; its transparent tissues enable direct visualization of crystal formation; and its low maintenance cost supports large-scale screening efforts. This research system provides a reproducible methodological reference with important implications for the internationalization of TCM.

Associate Professor Yiwen Wang stated, “This work bridges the gap between traditional medical knowledge and modern scientific methodologies. In future studies, we plan to further optimize the screening platform, apply it to other disease models, and accelerate the clinical translation of active TCM ingredients.” The team has applied for multiple invention patents and is actively pursuing partnerships with pharmaceutical companies for further development.

This interdisciplinary research team is led by Associate Professor Yiwen Wang from the School of Pharmaceutical Science and Technology, Tianjin University. First author Yunuo Ren (Master student) and co-first author Wen Zhang (Master student) contributed equally to the study. Other key contributors include Associate Professor Youxin Li (School of Pharmaceutical Science and Technology, Tianjin University), Dr. Dekun Wang (School of Medicine, Nankai University), and Dr. Weiwei Tang (School of Chemical Engineering and Technology, Tianjin University). Corresponding authors include Associate Professor Yiwen Wang, Director Shaoshan Du (Tianjin Jinnan Hospital), Researcher Zhimou Guo (Dalian Institute of Chemical Physics, Chinese Academy of Sciences), Professor Xiaoyue Tan (School of Medicine, Nankai University), and Professor Zhiguang Yuchi (School of Pharmaceutical Science and Technology, Tianjin University). The study also received technical support from the Instrument Testing Center of the School of Pharmaceutical Science and Technology, Tianjin University.

Original Article Link: https://doi.org/10.1016/j.jep.2025.119846

By: School of Pharmaceutical Science and Technology

Editor: Sun Xiaofang