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Broussonin A Attenuates Type 2 Diabetic Osteoporosis by Reactivating JAK2/STAT3 Signaling to Inhibit Ferroptosis in

Yangfan Guo1,2, Yixun Huang1,2, Lijiang Han1,2

  • 1Department of Orthopedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Phytotherapy Research : PTR
|July 4, 2026
PubMed

Insights

Broussonin A (BRA) combats type 2 diabetic osteoporosis by inhibiting ferroptosis and restoring bone health. It targets the JAK2/STAT3 pathway, offering a potential therapeutic strategy for this debilitating condition.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Type 2 diabetic osteoporosis (T2DOP) impairs bone health, partly via ferroptosis induced by glucolipotoxicity.
  • Therapeutic interventions targeting ferroptosis in T2DOP are underdeveloped.
  • Broussonin A (BRA), a natural antioxidant, has potential for bone metabolic disorders, but its role in T2DOP is unexamined.

Purpose of the Study:

  • To investigate whether BRA inhibits ferroptosis and improves bone quality in type 2 diabetic conditions.
  • To elucidate the molecular mechanisms underlying BRA's effects on T2DOP.

Main Methods:

  • Established in vivo (STZ/high-fat diet rats) and in vitro (high-glucose/high-lipid BMSCs) T2DOP models.
  • Assessed ferroptosis markers (Fe2+, lipid peroxidation), mitochondrial function, and osteogenic differentiation.
  • Utilized Western blotting, immunofluorescence, network pharmacology, and cellular thermal shift assays to identify molecular targets.

Main Results:

  • BRA reduced high-glucose/high-lipid-induced cytotoxicity, ferroptosis, and mitochondrial dysfunction in BMSCs.
  • BRA treatment improved osteogenic differentiation in vitro and preserved bone microarchitecture in vivo without toxicity.
  • BRA reactivated the JAK2/STAT3 pathway, increasing GPX4 expression, which was crucial for its protective effects.

Conclusions:

  • BRA effectively mitigates T2DOP by suppressing ferroptosis through the JAK2/STAT3 signaling pathway.
  • BRA demonstrates therapeutic potential for treating type 2 diabetic osteoporosis.
Keywords:
Broussonin AJAK2/STAT3 signaling pathwaybone marrow mesenchymal stem cellsferroptosismitochondrial dysfunctiontype 2 diabetic osteoporosis

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