Integrative Multi-Omics and Network Pharmacology Analyses Reveal Potential Mechanisms of Codonopsis pilosula in Mountain Sickness
5 affiliations
- 1State Key Laboratory Incubation Base for Conservation and Utilization of Bio-Resource in Tarim Basin, College of Life Sciences and Technology, Tarim University, Alar 843300, China
- 2College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China
- 3College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
- 4College of Life Science and Technology, Xinjiang University, Urumqi 830000, China
- 5College of Biological Sciences, China Agricultural University, Beijing 100193, China
Abstract
Mountain sickness comprises a spectrum of high-altitude disorders associated with hypobaric hypoxia, including acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE). Although Codonopsis pilosula has been widely used in traditional medicine for conditions related to hypoxia, its molecular basis in mountain sickness remains poorly understood. Here, we integrated network pharmacology, transcriptomic analysis, machine-learning-based feature selection, single-cell RNA sequencing, and molecular docking to explore potential molecular associations between Codonopsis pilosula-related candidate targets and mountain sickness. We identified a set of Codonopsis pilosula-associated candidate targets enriched in biological processes related to hypoxia response, oxidative stress, inflammation, and vascular regulation. Integrated transcriptomic analyses across high-altitude exposure, AMS, and HAPE revealed convergent alterations in immune-related and oxygen transport-associated programs. Machine-learning analysis further provided internal computational prioritization of candidate genes associated with high-altitude exposure, with recurrent selection across complementary algorithms within the analyzed paired cohort. Single-cell transcriptomic analysis provided additional cellular context for these candidates, revealing distinct expression patterns across peripheral blood and lung cell populations. Molecular docking further identified potential interactions between selected Codonopsis pilosula compounds and candidate proteins, with MMP9, CA2, and BCL2 showing comparatively favorable predicted interactions. Together, these findings provide an exploratory framework for evaluating potential associations between Codonopsis pilosula-associated candidate targets and transcriptional and cellular responses to high-altitude hypoxia, and identify candidate molecular pathways and targets for further experimental investigation.
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BibTeX
@article{zhou2026integrative,
title = {{Integrative Multi-Omics and Network Pharmacology Analyses Reveal Potential Mechanisms of Codonopsis pilosula in Mountain Sickness}},
author = {Yaqi Zhou and Jiamin Wu and Zhiwei Tan and Wanxin He and Wen Tan and Mingxue Fu and Baowei Bai and Hao Li},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209256},
url = {https://www.mdpi.com/1422-0067/27/20/9256},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrative Multi-Omics and Network Pharmacology Analyses Reveal Potential Mechanisms of Codonopsis pilosula in Mountain Sickness
AU - Yaqi Zhou
AU - Jiamin Wu
AU - Zhiwei Tan
AU - Wanxin He
AU - Wen Tan
AU - Mingxue Fu
AU - Baowei Bai
AU - Hao Li
PY - 2026
DA - 2026/10/18
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209256
UR - https://www.mdpi.com/1422-0067/27/20/9256
AB - Mountain sickness comprises a spectrum of high-altitude disorders associated with hypobaric hypoxia, including acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE). Although Codonopsis pilosula has been widely used in traditional medicine for conditions related to hypoxia, its molecular basis in mountain sickness remains poorly understood. Here, we integrated network pharmacology, transcriptomic analysis, machine-learning-based feature selection, single-cell RNA sequencing, and molecular docking to explore potential molecular associations between Codonopsis pilosula-related candidate targets and mountain sickness. We identified a set of Codonopsis pilosula-associated candidate targets enriched in biological processes related to hypoxia response, oxidative stress, inflammation, and vascular regulation. Integrated transcriptomic analyses across high-altitude exposure, AMS, and HAPE revealed convergent alterations in immune-related and oxygen transport-associated programs. Machine-learning analysis further provided internal computational prioritization of candidate genes associated with high-altitude exposure, with recurrent selection across complementary algorithms within the analyzed paired cohort. Single-cell transcriptomic analysis provided additional cellular context for these candidates, revealing distinct expression patterns across peripheral blood and lung cell populations. Molecular docking further identified potential interactions between selected Codonopsis pilosula compounds and candidate proteins, with MMP9, CA2, and BCL2 showing comparatively favorable predicted interactions. Together, these findings provide an exploratory framework for evaluating potential associations between Codonopsis pilosula-associated candidate targets and transcriptional and cellular responses to high-altitude hypoxia, and identify candidate molecular pathways and targets for further experimental investigation.
SN - 1422-0067
ER -