2. Academic Validation
  3. Cannabidiol Is a Potential Inhibitor of Ferroptosis in Human Articular Chondrocytes

Cannabidiol Is a Potential Inhibitor of Ferroptosis in Human Articular Chondrocytes

  • J Cell Mol Med. 2025 Jul;29(13):e70592. doi: 10.1111/jcmm.70592.
A Wipplinger 1 2,  D Bekric 1,  C Ablinger 3,  M Kittl 1 2,  C Mayr 1 4,  M Ritter 1 2 5,  M Winklmayr 1 2,  M Jakab 1 2
Affiliations

Affiliations

  • 1 Center of Physiology, Pathophysiology and Biophysics, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria.
  • 2 Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Salzburg, Austria.
  • 3 Institute of Pharmacy, Paracelsus Medical University, Salzburg, Austria.
  • 4 Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria.
  • 5 Gastein Research Institute, Paracelsus Medical University, Salzburg, Austria.
PMID: 40576283 DOI: 10.1111/jcmm.70592
Abstract

The present study investigates the effects of cannabidiol (CBD), the major non-psychoactive compound of Cannabis sativa L. extracts, on ferroptotic cell death in human articular chondrocytes. Exposure to known Ferroptosis inducers RSL3, erastin and its analogue IKE, FINO2 and FIN56 led to a varying extent of reduced cell viability in two chondrocyte cell lines (in C-28/I2, T/C-28/A2) and primary chondrocytes, suggesting different sensitivity and defence mechanisms towards the respective substances. The cytotoxic effects were aggravated by additional exposure to iron and inhibited by the specific Ferroptosis inhibitor ferrostatin-1 (Fer-1), proving the occurrence of Ferroptosis. Strikingly, co-treatment of Ferroptosis inducers with CBD clearly restored cell viability in a dose-dependent manner (10 nM to 1 μM CBD) in both cell lines and primary chondrocytes. Moreover, CBD restored the activity of GPX4, a major anti-oxidative enzyme, to varying degrees when combined with IKE or RSL3. Increasing evidence has emerged for an important role of iron dyshomeostasis and Ferroptosis in the onset and progression of various orthopaedic diseases, including osteoarthritis. Therefore, the here demonstrated and previously unreported cytoprotective and anti-oxidative effects of CBD in the context of Ferroptosis have highly promising therapeutic implications.

Keywords

CBD; OA; chondrocytes; ferroptosis; osteoarthritis; viability.

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