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Published on: February 28, 2025
Paeonia lactiflora-derived extracellular vesicles ameliorate diabetic peripheral neuropathy by modulating
Lihong Wang1, Shiyun Xia1, Shuqi Lin2
1Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Aims:
This study investigated the therapeutic potential of Paeonia lactiflora-derived extracellular vesicles (PRA-EVs) for diabetic peripheral neuropathy (DPN), with a particular focus on their immunomodulatory effects on the CC motif chemokine ligand 21 (CCL21) / CC chemokine receptor type 7 (CCR7) axis.
Methods:
PRA-EVs were isolated and characterized. In vitro, their effects on high glucose (HG)-induced Schwann cell apoptosis, CCL21 expression, and CD8⁺ T-cell migration were assessed. In vivo, therapeutic efficacy was evaluated in an STZ-induced DPN mouse model using behavioral testing, histological analysis, and molecular assays.
Results:
PRA-EVs significantly attenuated HG-induced Schwann cell apoptosis and reduced CCL21 expression. In DPN mice, PRA-EVs improved behavioral and structural abnormalities, including neuropathic pain and myelin injury, with efficacy comparable to mecobalamin. Mechanistically, PRA-EVs were associated with downregulation of CCL21/CCR7 signaling and reduced CCR7⁺CD8⁺ T-cell infiltration in sciatic nerves. In addition, PRA-EVs suppressed CD8⁺ T-cell migration to a degree comparable to the CCR7 pathway inhibitor Cosalane. To our knowledge, this is the first study to link PRA-EVs with the amelioration of DPN in association with modulation of the CCL21/CCR7 axis.
Conclusion:
PRA-EVs ameliorate DPN, at least in part, through modulation of the CCL21/CCR7 axis, thereby attenuating Schwann cell injury and neuroinflammation. These findings support PRA-EVs as a promising multi-target therapeutic strategy for DPN.
