Background: Oxidative stress promotes apoptosis and disrupts the osteogenic differentiation of mesenchymal stem cells, contributing to osteoporosis and increased bone fragility. Given its antioxidant activity, fucoxanthin was evaluated in this study for its ability to protect placenta-derived mesenchymal stem cells (PL-MSCs) from oxidative damage and to maintain their capacity to differentiate into bone-forming cells.

Methods: Placental tissues from healthy donors following normal delivery were used to isolate and characterize PL-MSCs. The cells were then treated with 750 µM H₂O₂ for 24 h, with or without 1–5 µM fucoxanthin. Viability was evaluated by MTT assay; antioxidant activity was assessed by measuring intracellular ROS and antioxidant enzyme activities. Apoptosis was determined using Annexin V/PI staining, and apoptosis-related genes and proteins were analyzed by qRT-PCR and Western blot. Gene expression changes and pathways underlying fucoxanthin’s cytoprotection were profiled using the NanoString nCounter platform. For osteogenic assessment, PL-MSCs were cultured in osteogenic medium containing 200 µM H₂O₂ and 1–3 µM fucoxanthin for 28 days, followed by assays of alkaline phosphatase (ALP) activity and Alizarin Red staining.

Results: Fucoxanthin increased viability and boosted antioxidant enzyme activity in PL-MSCs under oxidative stress, while decreasing intracellular ROS. It also diminished apoptosis in H₂O₂-treated cells and lowered the expression of apoptosis-associated markers. Transcriptomic profiling indicated upregulation of genes linked to cell survival, including cell cycle progression and DNA repair, alongside downregulation of pro-apoptotic pathways. Under osteogenic conditions, fucoxanthin enhanced ALP activity and mineralization compared with H₂O₂ alone.

Conclusions: Fucoxanthin protects PL-MSCs from oxidative damage by mitigating ROS, suppressing apoptosis, and promoting survival-related gene expression. It also preserves and improves osteogenic differentiation under oxidative stress. These findings support further investigation of fucoxanthin as a potential preventive or therapeutic option for osteoporosis.