Integrative network pharmacology and transcriptomics suggest the mechanism of Buyang Huanwu Decoction in attenuating vascular aging via AMPK signaling pathway

Objective

Vascular aging is a critical factor in cardiovascular diseases. Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine, shows potential in delaying vascular aging, yet its mechanisms remain unclear. This study aims to explore BYHWD's pharmacological mechanisms through integrative network pharmacology and transcriptomics.

Methods

Network pharmacology identified BYHWD targets related to aging, followed by pathway enrichment analysis. Vascular histopathology was evaluated using HE, Masson, and EVG staining. Senescence biomarkers SA-β-gal, advanced glycation end products (AGEs), p16, p21, and p53 were determined. Oxidative-inflammatory markers were quantified via ELISA and RT-qPCR. Transcriptomic profiling used Illumina NovaSeq. AMP-activated protein kinase (AMPK) signaling pathway analysis employed immunohistochemistry.

Results

Network pharmacology identified 103 key targets, including SIRT1 and AMPK, related to oxidative stress and inflammation. In the D-galactose-induced aging model rats, BYHWD treatment significantly reduced vascular media thickness by 28% in the medium-dose group, collagen deposition, and markers of senescence, such as SA-β-gal, AGEs, p16, p21, and p53. Transcriptomics revealed AMPK signaling pathway enrichment, and further experiments revealed that BYHWD mediates its effects involving activation of the AMPK/Sirt1/Foxo3a axis, a key regulator of vascular homeostasis.

Conclusion

BYHWD may attenuate vascular aging by AMPK-mediated regulation of oxidative stress and inflammation, providing a novel multi-target strategy against age-related cardiovascular diseases. The underlying molecular mechanism still needs to be further clarified.