# Tanshinone IIA accelerates zebrafish venous vascular repair via macrophage recruitment through the CXCR4A–CXCL12B signaling axis

**Authors:** Li Zhang, Lijuan An, Yanchi Zhao, Zheng Lu, Jiangtao Huang, Lingling Tang, Mengzhu Lv, Dashuang Mo, Liping Shu

PMC · DOI: 10.3389/fimmu.2026.1792022 · 2026-03-19

## TL;DR

Tanshinone IIA from Salvia miltiorrhiza helps repair blood vessels in zebrafish by boosting macrophage activity through a specific signaling pathway.

## Contribution

Identifies Tanshinone IIA as a novel compound that accelerates vascular repair via the CXCR4A–CXCL12B signaling axis in zebrafish.

## Key findings

- Tanshinone IIA promotes macrophage migration to vascular injury sites via the CXCR4A–CXCL12B axis.
- The compound enhances vascular repair by increasing cytokine release (IL-10 and TGFB1A) from macrophages.
- Salvia miltiorrhiza compounds show pro-angiogenic properties in zebrafish models.

## Abstract

Vascular injury is a major contributor to the development of cardiovascular diseases. Following vascular damage, macrophages migrate to the injury site and, during the later stages of vascular repair, secrete cytokines such as interleukin-10 (IL-10) and transforming growth factor-β1a (TGFB1A), thereby promoting vascular regeneration. Previous studies have demonstrated that macrophage recruitment to sites of tissue injury is mediated by the CXCR4A-CXCL12B signaling axis. In a screening of traditional Chinese medicinal herbs for cardiovascular therapeutic potential, Salvia miltiorrhiza root was identified as a promising source of bioactive compounds capable of enhancing vascular repair through modulation of the CXCR4A-CXCL12B axis.

Establishing a vascular injury model in transgenic zebrafish lines Tg (flk1:eGFP; gata1:dsRed) using a two-photon microscopy laser system. Dynamic monitoring of vascular repair via two-photon microscopy. Evaluate macrophage migration capacity in a Tg (mpeg1:eGFP) zebrafish vascular injury model using confocal microscopy. Detection of il-10 and tgfb1a expression released by macrophages via qPCR experiments. Detect CXCR4A-CXCL12B expression at the site of zebrafish vascular injury via fluorescence in situ hybridization coupled with antibody staining.

We confirm that compounds from the selected extract promote macrophage migration to vascular injury sites by upregulating the CXCR4A-CXCR12B signaling axis. This process accelerates repair of damaged blood vessels in zebrafish by inducing the release of cytokines such as il-10 and tgfb1a.

This study confirms that Salvia miltiorrhiza, a traditional Chinese medicinal plant, is a valuable source of bioactive compounds with pro-angiogenic properties. Our findings provide scientific support for the traditional use of Salvia miltiorrhiza active components in treating vascular injuries.

## Linked entities

- **Genes:** cxcr4a (chemokine (C-X-C motif) receptor 4a) [NCBI Gene 140747], cxcl12b (chemokine (C-X-C motif) ligand 12b (stromal cell-derived factor 1)) [NCBI Gene 799354], IL10 (interleukin 10) [NCBI Gene 3586], tgfb1a (transforming growth factor, beta 1a) [NCBI Gene 359834], MPEG1 (macrophage expressed 1) [NCBI Gene 219972], KDR (kinase insert domain receptor) [NCBI Gene 3791], GATA1 (GATA binding protein 1) [NCBI Gene 2623]
- **Chemicals:** Tanshinone IIA (PubChem CID 164676)
- **Species:** Danio rerio (taxon 7955)

## Full-text entities

- **Genes:** gata1a (GATA binding protein 1a) [NCBI Gene 30481] {aka gata1, gta1, sb:eu551, vlt, zg1}, mpeg1.1 (macrophage expressed 1, tandem duplicate 1) [NCBI Gene 335407] {aka fj09e08, mpeg1, wu:fb14d06, wu:fj09e08, zgc:66409}, cxcl12b (chemokine (C-X-C motif) ligand 12b (stromal cell-derived factor 1)) [NCBI Gene 799354] {aka SDF1b, cxc112b, sdf-1b, zgc:136720}, cxcr4a (chemokine (C-X-C motif) receptor 4a) [NCBI Gene 140747] {aka cb824}, il10 (interleukin 10) [NCBI Gene 553957] {aka zgc:194510, zgc:194518}, tgfb1a (transforming growth factor, beta 1a) [NCBI Gene 359834] {aka ai39657, tgfb1, wu:fb13a07, xx:ai39657}, kdr (kinase insert domain receptor (a type III receptor tyrosine kinase)) [NCBI Gene 554230] {aka flk1, flk1b, kdrb, si:busm1-205d10.1, si:ch211-254j6.1, si:ch211-278f21.4}
- **Diseases:** cardiovascular diseases (MESH:D002318), Vascular injury (MESH:D057772), tissue injury (MESH:D017695)
- **Chemicals:** eGFP (-), Tanshinone IIA (MESH:C021751)
- **Species:** Danio rerio (leopard danio, species) [taxon 7955], Salvia miltiorrhiza (Chinese salvia, species) [taxon 226208]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13043380/full.md

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Source: https://tomesphere.com/paper/PMC13043380