# The traditional Chinese medicine formula Zhihan Anshen Tang (ZHAST) against obstructive sleep apnea hypopnea syndrome: network pharmacology and molecular docking approach

**Authors:** Cai-Li Li, Yu-Xiang Zhang, Xing-Jie Zheng, Shuo Li, Jing Feng

PMC · DOI: 10.3389/fchem.2025.1524087 · Frontiers in Chemistry · 2025-03-10

## TL;DR

This study explores how a traditional Chinese medicine, Zhihan Anshen Tang, may treat sleep apnea by identifying its key ingredients and mechanisms using modern research methods.

## Contribution

This is the first network pharmacology and molecular docking study on a Chinese medicine for obstructive sleep apnea.

## Key findings

- Key targets like TNF, IL6, and STAT3 are involved in ZHAST's mechanism against OSAHS.
- ZHAST affects inflammatory and hypoxia-related pathways, including MAPK and AGE-RAGE signaling.
- Enoxolone in ZHAST shows high affinity with relevant targets through molecular docking.

## Abstract

The current treaments for Obstructive Sleep Apnea Hypopnea (OSAHS) are Continuous Positive Airway Pressure (CPAP) and lifestyle modifications, which is not suitable for all patients. Traditional Chinese medicine (TCM) has increasingly demonstrated its efficacy and benefits in treating OSAHS. Zhihan Anshen Tang (ZHAST), has been demonstrated its efficacy and clinical metrics for treating OSAHS patients. However, its key ingredients and mechanisms of action are still unknown.

Using network pharmacology, we investigated the potential mechanisms of ZHAST through which OSAHS.

In addition, the key targets, including TNF, IL6, GAPDH, STAT3, HIF1A, and JUN, are revealed by the topological analysis. According to the findings of the GO enrichment analysis, genes were enriched in inflammatory responses, hypoxia responses, positive regulation of angiogenesis, protein phosphorylation, and regulation of cell proliferation. KEGG pathway enrichment analysis suggests that the signaling pathway of ZHAST in OSAHS are MAPK and AGE-RAGE signaling pathway, especially in diabetic complications. In addition, it is demonstrated that the enoxolone in ZHASTs have high affinity with the relevant targets by molecular docking and molecular dynamics simulations.

To my knowledge, this is the first network pharmacological molecular docking study about a Chinese medicine effective against OSA. This investigation integrates molecular docking and network pharmacology to identify the effective compounds, related targets, and potential mechanism of ZHASTs in the treatment of OSAHS, providing the prospect of traditional Chinese medicines with modern medical research.

## Linked entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124], IL6 (interleukin 6) [NCBI Gene 3569], GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774], HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091], JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725]
- **Chemicals:** enoxolone (PubChem CID 10114)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, RENBP (renin binding protein) [NCBI Gene 5973] {aka RBP, RNBP}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MOK (MOK protein kinase) [NCBI Gene 5891] {aka RAGE, RAGE-1, RAGE1, STK30}
- **Diseases:** diabetic complications (MESH:D048909), OSAHS (MESH:D020181), OSA (MESH:C535586), inflammatory (MESH:D007249), hypoxia (MESH:D000860)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

14 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11931058/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC11931058/full.md

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Source: https://tomesphere.com/paper/PMC11931058