2. Academic Validation
  3. Poliumoside protects against type 2 diabetes-related osteoporosis by suppressing ferroptosis via activation of the Nrf2/GPX4 pathway

Poliumoside protects against type 2 diabetes-related osteoporosis by suppressing ferroptosis via activation of the Nrf2/GPX4 pathway

  • Phytomedicine. 2024 Mar:125:155342. doi: 10.1016/j.phymed.2024.155342.
Chao-Yi Xu 1,  Chun Xu 2,  Yi-Ning Xu 3,  Shi-Qi Du 4,  Zi-Han Dai 4,  Shu-Qing Jin 4,  Gang Zheng 5,  Cheng-Long Xie 6,  Wen-Lai Fang 7
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 2 Department of Pathology, Cixi Maternity and Child Health Care Hospital, Cixi 315300, China.
  • 3 Department of Orthopedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, China.
  • 4 The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, China.
  • 5 Department of Orthopedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: [email protected].
  • 6 Department of Orthopedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: [email protected].
  • 7 Department of Orthopedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: [email protected].
PMID: 38295665 DOI: 10.1016/j.phymed.2024.155342
Abstract

Background: Type 2 diabetes is often linked with osteoporosis (T2DOP), a condition that accelerates bone degeneration and increases the risk of fractures. Unlike conventional menopausal osteoporosis, the diabetic milieu exacerbates the likelihood of fractures and osteonecrosis. In particular poliumoside (Pol), derived from Callicarpa kwangtungensis Chun, has shown promising anti-oxidant and anti-inflammatory effects. Yet, its influence on T2DOP remains to be elucidated.

Purpose: The focus of this study was to elucidate the influence of Pol in HGHF-associated Ferroptosis and its implications in T2DOP.

Study design: A murine model of T2DOP was established using a minimal dosage of streptozotocin (STZ) through intraperitoneal infusion combined with a diet high in fat and sugar. Concurrently, to mimic the diabetic condition in a lab environment, bone mesenchymal stem cells (BMSCs) were maintained in a high-glucose and high-fat (HGHF) setting.

Methods: The impact of Pol on BMSCs in an HGHF setting was determined using methods, such as BODIPY-C11, FerroOrange staining, mitochondrial functionality evaluations, and Western blot methodologies, coupled with immunoblotting and immunofluorescence techniques. To understand the role of Pol in a murine T2DOP model, techniques including micro-CT, hematoxylin and eosin (H&E) staining, dual-labeling with calcein-alizarin red, and immunohistochemistry were employed for detailed imaging and histological insights.

Results: Our findings suggest that Pol acts against HGHF-induced bone degradation and Ferroptosis, as evidenced by an elevation in glutathione (GSH) and a decline in malondialdehyde (MDA) levels, lipid peroxidation, and mitochondrial Reactive Oxygen Species (ROS). Furthermore, Pol treatment led to increased bone density, enhanced GPX4 markers, and reduced ROS in the distal femur region. On investigating the underlying mechanism of action, it was observed that Pol triggers the Nrf2/GPX4 pathway, and the introduction of lentivirus-Nrf2 negates the beneficial effects of Pol in HGHF-treated BMSCs.

Conclusion: Pol is effective in treating T2DOP by activating the Nrf2/GPX4 signaling pathway to inhibit Ferroptosis.

Keywords

Ferroptosis; Mitochondria function; Nrf2/GPX4 pathway; Poliumoside; Type 2 diabetic osteoporosis.

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