# Nobiletin promotes fracture healing by modulating macrophage polarization: a review

**Authors:** Zhiqi Zhang, Shangyi Liu, Wenhao Li, Kangquan Shou

PMC · DOI: 10.3389/fphar.2025.1724568 · Frontiers in Pharmacology · 2026-01-06

## TL;DR

This review explores how nobiletin helps heal fractures by changing macrophage behavior.

## Contribution

The paper reviews nobiletin's novel role in modulating macrophage polarization to enhance fracture healing.

## Key findings

- Nobiletin promotes M2 macrophage polarization, which aids tissue repair.
- It reduces M1 macrophage activity, decreasing inflammation during healing.
- Nobiletin shows potential as a therapeutic agent for fracture recovery.

## Abstract

Fracture healing is a complex process in which various cells, including macrophages, are involved. M1 macrophages and the cytokines they secrete exacerbate local inflammation and inhibit fracture healing, whereas M2 macrophages inhibit inflammation and promote tissue repair. An imbalance in the ratio of M1 to M2 macrophages leads to delayed healing and nonunion of the fracture. Nobiletin has received increasing attention in promoting fracture healing. Thus, the aim of this review article was to investigate the effects of nobiletin on macrophages during fracture healing, with a major focus on the potential mechanisms and applications, and to provide a reference for further research on this compound.

## Linked entities

- **Chemicals:** nobiletin (PubChem CID 72344)

## Full-text entities

- **Diseases:** inflammation (MESH:D007249), Fracture (MESH:D050723), nonunion (MESH:C538144)
- **Chemicals:** Nobiletin (MESH:C008661)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12816298/full.md

## References

105 references — full list in the complete paper: https://tomesphere.com/paper/PMC12816298/full.md

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Source: https://tomesphere.com/paper/PMC12816298