The exploration of the effect and mechanism of Shengxian decoction inhibiting acute high-altitude myocardial injury.

BACKGROUND

The heart is the most vulnerable organ to acute hypobaric hypoxia exposure, acute high-altitude myocardial injury (AHMI) typically occurs in individuals who rapidly ascend from lowland areas to high-altitude regions. Effective intervention strategies for AHMI have garnered significant attention, with Shengxian decoction (SXD) emerging as a potential therapeutic agent; however, the underlying mechanism remains unclear.

PURPOSE: The objective of this study was to explore the effective components, potential targets and regulatory mechanisms of SXD in improving AHMI.

STUDY

DESIGN

This study innovatively employed the combined strategy including network pharmacology, transcriptomics, proteomics, molecular docking, and molecular biology to analyze the targets and mechanism pathways of SXD for improving AHMI. Ultra-high-performance liquid chromatography/Q Exactive HFX mass spectrometry (UHPLC-QE-MS) and network pharmacology were adopted to identify active ingredients and analyze their functions. On this basis, transcriptomics and proteomics technologies were integrated to further investigate and validate the mechanisms at both gene and protein levels. Additionally, a herbs-components-targets-pathways (HCTP) network was generated for exploration and analysis. Molecular docking was utilized for an in-depth examination of the binding activity between screened components and targets. Finally, molecular biology techniques were applied to re-confirm the targets and mechanisms involved.

RESULTS

SXD effectively reduced heart's abnormal electrical activity, inhibited the release of various myocardial enzymes, troponins and inflammatory factors into the blood. Network pharmacology, transcriptomics, proteomics revealed that inflammatory response was important for the effects of SXD in AHMI. The combined analysis of network pharmacology, transcriptomics, proteomics constructed the HCTP network encompassing 5 herbs, 13 active ingredients, 146 targets and 20 signaling pathways to elucidate the mechanism by which SXD exerts its effects on AHMI, further analysis suggested that SXD regulated IL-17, MAPK/ERK, and Ras signaling pathways to alleviate AHMI.

CONCLUSION

The positive effect of SXD on AHMI was achieved through the regulation of inflammation-related pathways (IL-17, MAPK/ERK, and Ras signaling pathways), the inhibition of inflammatory factors releases and the modulation of the inflammatory response.