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Network pharmacology prediction, molecular docking and in vitro experiment explored the potential mechanism of Gaoyuan’an capsule in improving hypoxia tolerance

The Pharmacogenomics Journal volume 24, Article number: 8 (2024) Cite this article

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Abstract

Background

Tibetan medicine Gaoyuan’an capsule (GYAC) is widely used to prevent pulmonary edema at high altitude, but the specific mechanism has not been explored. In this study, we analyzed the mechanism of GYAC in hypoxia tolerance, and provided a new idea for the prevention and treatment of altitude disease.

Methods

The effective components and corresponding targets of GYAC were screened out by the Chinese herbal medicine network database, and the key targets of hypoxia tolerance were retrieved by Genecards, OMIM and PubMed database. Cytoscape 3.7.2 was used to construct GYAC ingredient-target-hypoxia tolerance-related target network. GO function annotation and KEGG enrichment analysis were performed to predict the pathways in which target genes may be involved, and molecular docking was used to verify the binding ability of the compound to target genes. In vitro, the above results were further verified by molecular experiment.

Results

We found that GYAC can improve hypoxia tolerance by regulating various target genes, including IL6, IFNG, etc. The main regulatory pathways were HIF-1 signaling pathway. Molecular docking showed that the affinity between luteolin and target genes (IL6, IFNG) were better. In vitro, we observed that hypoxia can inhibit cell viability and promote apoptosis of H9C2 cell. And hypoxia can promote the expression of LDH. After the addition of luteolin, the decrease of cell viability, the increase of cell apoptosis, LDH release and the decrease of mitochondrial membrane potential were inhibited. Besides, inflammatory related factors (IL-6, IL-10, IL-2, IFNG and VEGFA) expression were also inhibited hypoxic cell models.

Conclusions

The results of network pharmacology and molecular docking showed that luteolin, a monomeric component of GYAC, played a role in hypoxia tolerance through a variety of target genes, such as IL6, IFNG. What’s more, we have discovered that luteolin can reduce the inflammatory response in cardiac myocytes, thereby alleviating mitochondrial damage, and ultimately enhancing the hypoxia tolerance of H9C2 cardiomyocytes.

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Fig. 1: Network pharmacology identified ingredients and targets of GYAC and hypoxia tolerance-related targets and Protein-protein interaction (PPI) network.
Fig. 2: Molecular docking experiments between luteolin and common targets.
Fig. 3: Construction of hypoxic tolerance model of H9C2 cardiomyocytes.
Fig. 4: Luteolin can improve hypoxia tolerance by reducing the inflammatory response and lowering mitochondrial damage of H9C2 cardiomyocytes.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

We thank all authors for their contributions and supports.

Funding

Natural Science Foundation of Tibet Autonomous Region (XZ202201ZR0048G),  Science and Technology Major Project of Tibetan Autonomous Region of China (XZ202201ZD0001G) and Key R&D Program of Xizang (Tibet) Autonomous Region (XZ202101ZY0018G).

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Authors and Affiliations

  1. School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi, 712082, China

    Tianbo Jin, Xiaoli Liu, Yijin Qi, Xuemei Li, Li Wang & Xue He

  2. Department of Clinical Laboratory, the Affiliated Hospital of Xizang Minzu University, Xianyang, Shaanxi, 712082, China

    Yuhe Wang

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  1. Tianbo Jin
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Contributions

Tianbo Jin wrote the manuscript; Xiaoli Liu and Yuhe Wang analyzed the data; Yijin Qi and Xuemei Li made tables and figures; Li Wang and Xue He provided research ideas.

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Correspondence to Xue He.

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The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by Research Ethics Committee of Xizang Minzu University. Written informed consent was obtained from individual or guardian participants.

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Jin, T., Liu, X., Wang, Y. et al. Network pharmacology prediction, molecular docking and in vitro experiment explored the potential mechanism of Gaoyuan’an capsule in improving hypoxia tolerance. Pharmacogenomics J 24, 8 (2024). https://doi.org/10.1038/s41397-024-00327-0

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