# Integrated Network Pharmacology, Single‐Cell Transcriptomics Unveil the Mechanistic Role of Morusin in Aortic Dissection

## TL;DR

This study explores how morusin, a natural compound, may help treat aortic dissection by targeting multiple pathways and cell types.

## Contribution

The study integrates network pharmacology and single-cell transcriptomics to reveal morusin's multi-target mechanisms in aortic dissection.

## Key findings

- Morusin targets 84 overlapping genes linked to aortic dissection and affects IL-17, HIF-1, and MAPK pathways.
- Single-cell analysis shows cell-type-specific dysregulation, including MAPK8 upregulation in fibroblasts and immune cells.
- Morusin reduces aortic dilation and improves survival in a mouse model of aortic dissection.

## Abstract

Aortic dissection is a life‐threatening cardiovascular emergency with limited pharmacological options. This study focuses on elucidating the multi‐target and multi‐pathway mechanisms through which morusin mitigates aortic dissection progression, integrating network pharmacology, single‐cell transcriptomics and experimental validation. Multi‐database analysis identified 281 morusin targets and 1741 ad‐related genes, with 84 overlaps. Enrichment analyses highlighted IL‐17, HIF‐1 and MAPK signalling pathways as potential regulatory hubs. Protein–protein interaction network analysis identified seven key targets, all showing high binding affinity to morusin in molecular docking. Single‐cell transcriptomics revealed cell‐type‐specific dysregulation, notably MAPK8 upregulation in fibroblasts and immune cells. In vitro, morusin dose‐dependently inhibited AngII‐induced vascular smooth muscle cell proliferation and modulated IL‐17 pathway gene expression. In vivo, morusin attenuated aortic dilation and reduced morbidity and mortality in a BAPN‐induced AD mouse model. These findings suggest that morusin mitigates AD progression by targeting key inflammatory and apoptotic pathways, supporting its potential as a multi‐target therapeutic candidate.