Understanding the molecular basis of herbal medicines for cough variant asthma under the guidance of traditional herbal theories

Rui Liu¹Jiaqi Yao¹Yihang Sui¹Yinnan Zhang¹Seng Kho¹Yingli Zhu²Ninghua Tan¹Yinyin Wang^1*

• ¹China Pharmaceutical University, Nanjing, China
• ²Beijing University of Chinese Medicine, Beijing, Beijing Municipality, China

Despite of the obvious clinical efficacy of herbal formula Suhuang for cough variant asthma (CVA), the underlying mechanisms of action (MOAs) are not fully understood. As TCM is a unique system under the guide of traditional herbal theories for disease treatment, we here aimed to decipher the how herbal medicine play therapeutic effects on CVA disease under the guidance of TCM theories based on their transcriptional perturbation. To achieve this goal, we offer a new paradigm for understanding the molecular basis of herbal medicines by integrating gene perturbation data, GNN models, and network proximity methods within the framework of herbal medicine theories. We found that traditional herbal theories are closely related to their efficacy: 1) Meridian classifications of one herb are closely related to its gene perturbation distribution in different organs; 2) Herbal combination and their therapeutic effects are closely related to their target network proximity. Especially, network proximity analysis between molecular targets and disease-specific genes revealed the essence of "JUN-CHEN-ZUO-SHI" theory and lung-large intestine theories; 3) Using traditional herbal theories as features, we also developed two graph neural network models for herb-disease association and herb-herb combination prediction to identify potential active ingredients and combinations for CVA disease. In summary, our study offers a paradigm for understand the molecular basis of herbal medicines as well as their combinations for CVA disease with computational methods from the review of herbal theories.