2. Academic Validation
  3. Crocin facilitates peripheral nerve regeneration through modulation of the STAT3/Bcl-2/Beclin-1 signaling axis-mediated autophagic pathway

Crocin facilitates peripheral nerve regeneration through modulation of the STAT3/Bcl-2/Beclin-1 signaling axis-mediated autophagic pathway

  • Int Immunopharmacol. 2025 Sep 5:165:115437. doi: 10.1016/j.intimp.2025.115437.
Dongbo Tian 1,  Yixin Bo 1,  Jiahao Ying 2,  Dun Deng 1,  Jialuo Zhang 1,  Shuchang Lu 3,  Jingfei Xie 3,  Zipu Hong 4
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, China.
  • 2 The Third Affiliated Hospital of Wenzhou Medical University, No. 108 Wansong Road, Ruian, Wenzhou, Zhejiang 325200, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou 325000, China.
  • 3 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou 325000, China.
  • 4 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, China. Electronic address: hzp120119@163.com.
PMID: 40913861 DOI: 10.1016/j.intimp.2025.115437
Abstract

Peripheral nerve injury (PNI) is notoriously difficult to repair due to impaired axonal regeneration and dysregulated inflammatory microenvironments. This study demonstrates that crocin facilitates peripheral nerve regeneration by modulating the STAT3/Bcl-2/Beclin-1 signaling axis, enhancing Autophagy while suppressing NLRP3 inflammasome-mediated Pyroptosis. In a rat model of sciatic nerve crush injury, crocin treatment improved axonal regrowth and ultrastructural remyelination, as evidenced by upregulated expression of β3-Tubulin, neurofilament-200 (NF200), and myelin basic protein (MBP), alongside significantly elevated sciatic functional index (SFI) scores, reduced muscle atrophy, and diminished Collagen deposition. Mechanistically, crocin attenuated mitochondrial dysfunction by reducing mitochondrial ROS (mtROS) and restoring membrane potential (ΔΨm), thereby inhibiting NLRP3/GSDMD-dependent Pyroptosis. Molecular docking identified STAT3 as a pivotal target, while Western blot and immunofluorescence confirmed marked downregulation of pyroptosis-related proteins (NLRP3, GSDMD, and IL-1β). To our knowledge, this is the first study to elucidate crocin's dual role in orchestrating autophagy-pyroptosis crosstalk to accelerate nerve repair, offering a multi-target natural compound-based strategy for PNI therapy.

Keywords

Autophagy; Crocin; NLRP3 inflammasome; Pyroptosis.

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