Herb-CMap: a multimodal fusion framework for deciphering the mechanisms of action in traditional Chinese medicine using Suhuang antitussive capsule as a case study.

Publisher: Oxford University Press Country of Publication: England NLM ID: 100912837 Publication Model: Print Cited Medium: Internet ISSN: 1477-4054 (Electronic) Linking ISSN: 14675463 NLM ISO Abbreviation: Brief Bioinform Subsets: MEDLINE

Publication: Oxford : Oxford University Press
Original Publication: London ; Birmingham, AL : H. Stewart Publications, [2000-

Drugs, Chinese Herbal*/pharmacology ; Drugs, Chinese Herbal*/therapeutic use ; Medicine, Chinese Traditional*/methods ; Antitussive Agents*/pharmacology ; Antitussive Agents*/therapeutic use; Animals ; Rats ; Protein Interaction Maps/drug effects ; Asthma/drug therapy ; Asthma/metabolism ; Asthma/genetics ; Signal Transduction/drug effects ; Cough/drug therapy ; Transcriptome ; Humans

Herbal medicines, particularly traditional Chinese medicines (TCMs), are a rich source of natural products with significant therapeutic potential. However, understanding their mechanisms of action is challenging due to the complexity of their multi-ingredient compositions. We introduced Herb-CMap, a multimodal fusion framework leveraging protein-protein interactions and herb-perturbed gene expression signatures. Utilizing a network-based heat diffusion algorithm, Herb-CMap creates a connectivity map linking herb perturbations to their therapeutic targets, thereby facilitating the prioritization of active ingredients. As a case study, we applied Herb-CMap to Suhuang antitussive capsule (Suhuang), a TCM formula used for treating cough variant asthma (CVA). Using in vivo rat models, our analysis established the transcriptomic signatures of Suhuang and identified its key compounds, such as quercetin and luteolin, and their target genes, including IL17A, PIK3CB, PIK3CD, AKT1, and TNF. These drug-target interactions inhibit the IL-17 signaling pathway and deactivate PI3K, AKT, and NF-κB, effectively reducing lung inflammation and alleviating CVA. The study demonstrates the efficacy of Herb-CMap in elucidating the molecular mechanisms of herbal medicines, offering valuable insights for advancing drug discovery in TCM.
(© The Author(s) 2024. Published by Oxford University Press.)

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317680 Academy of Finland; BK20231024 Jiangsu Province Science Foundation for Youths; CPU2018GF05 China Pharmaceutical University

Keywords: cough variant asthma (CVA); gene perturbation network; herbal medicine; mechanisms of action (MOAs); multimodal data fusion; network-based heat diffusion algorithm; traditional Chinese medicine (TCM)

0 (Drugs, Chinese Herbal)
0 (Antitussive Agents)

Date Created: 20240729 Date Completed: 20240729 Latest Revision: 20240731

20240731

PMC11285169

10.1093/bib/bbae362

39073832