2. Academic Validation
  3. Asiatic acid induces ferroptosis of RA-FLS via the Nrf2/HMOX1 pathway to relieve inflammation in rheumatoid arthritis

Asiatic acid induces ferroptosis of RA-FLS via the Nrf2/HMOX1 pathway to relieve inflammation in rheumatoid arthritis

  • Int Immunopharmacol. 2024 Jun 8:137:112394. doi: 10.1016/j.intimp.2024.112394.
Miao Sun 1,  Qian Wang 1,  Jianhua Huang 2,  Qixuan Sun 1,  Qian Yu 3,  Xin Liu 4,  Zhining Liu 5
Affiliations

Affiliations

  • 1 Key Surgical Laboratory of Educational Administration of Liaoning Province, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121012, China; Post Graduate School of Jinzhou Medical University, Jinzhou 121001, China.
  • 2 Key Surgical Laboratory of Educational Administration of Liaoning Province, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121012, China. Electronic address: hjhuadr@163.com.
  • 3 Post Graduate School of Jinzhou Medical University, Jinzhou 121001, China; Huludao Central Hospital Teaching Base of Jinzhou Medical University, Jinzhou 125001, China.
  • 4 Key Surgical Laboratory of Educational Administration of Liaoning Province, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121012, China; Huludao Central Hospital Teaching Base of Jinzhou Medical University, Jinzhou 125001, China. Electronic address: LYY66112@163.com.
  • 5 Key Surgical Laboratory of Educational Administration of Liaoning Province, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121012, China; Ultrasound Department, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China. Electronic address: liuzhiningfuyi@163.com.
PMID: 38852517 DOI: 10.1016/j.intimp.2024.112394
Abstract

Background: Ferroptosis is a distinct iron-dependent non-apoptotic type of programmed cell death that is implicated in the pathophysiology of rheumatoid arthritis (RA). Although asiatic acid (AA) is documented to have significant anti-inflammatory effects in various diseases, it is not known whether it can regulate RA via Ferroptosis.

Methods: The effects of AA on rheumatoid arthritis fibroid-like synoviocytes (RA-FLS) were assessed in vitro, and a rat model of type II collagen-induced arthritis (CIA) was established to evaluate the effectiveness of AA treatment in vivo.

Results: AA significantly reduced both viability and colony formation in cultured RA-FLS, while increasing the levels of Reactive Oxygen Species (ROS), ferrous iron (Fe2+), malondialdehyde (MDA), and Lactate Dehydrogenase (LDH), as well as the expression of COX2. Furthermore, AA induced Ferroptosis in RA-FLS by promoting Fe2+ accumulation through downregulation of the expression of Keap1 and FTH1 and upregulation of Nrf2 and HMOX1. In vivo, AA treatment was found to reduce toe swelling and the arthritis score in CIA rats, as well as relieve inflammation and ankle damage and significantly upregulate the expression of Nrf2 and HMOX1 in the synovial fluid.

Conclusion: Treatment with AA significantly reduced the viability of RA-FLS and triggered Ferroptosis by promoting accumulation of Fe2+via the Nrf2-HMOX1 pathway, and was effective in relieving inflammation in CIA model rats. These findings suggest that the use of AA may be a promising strategy for the clinical treatment of RA.

Keywords

Asiatic acid; Collagen-induced arthritis rats; Ferroptosis; Rheumatoid arthritis.

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