73: Ginsenoside Rd Attenuates Spinal Cord Surgery Injury via the ROS/TXNIP/NLRP3 Inflammasome Axis

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic postsurgical pain, , , , , , , , Neuroimmunology, Pharmacological interventions, Omics (Proteomics/Metabolomics/Transcriptomics/Genomics),

Background and Aims: Surgical decompression for degenerative cervical myelopathy can induce spinal cord ischemia-reperfusion injury, contributing to postoperative neuroinflammation, neuronal injury, and chronic pain-like functional impairment. This process is driven by oxidative/ER stress and subsequent NLRP3 inflammasome activation via the ROS/TXNIP axis, a pathway strongly associated with central sensitization and neuropathic pain. Ginsenoside Rd (Rd), a natural compound with anti-inflammatory potential, was investigated for its capacity to attenuate surgery-induced neuroinflammation, reduce behavioral hypersensitivity, and enhance functional recovery by targeting the ROS/TXNIP/NLRP3 signaling in a rat model of cervical spinal cord decompression.

Methods: Anti-inflammatory effects of Ginsenoside Rd (Rd) were assessed in vitro using LPS-stimulated BV2 microglia and RAW264.7 macrophages. Transcriptomic analysis (RNA-seq) identified affected pathways. A rat model of cervical spinal cord compression at C5–C6 followed by decompression surgery was established. Postoperatively, rats were treated daily with Rd (5, 10, or 20 mg/kg, i.p.) or vehicle for four weeks. Motor recovery was evaluated using BBB locomotor scores, open field, and rotarod tests. Spinal cord tissues were analyzed for oxidative stress (DHE staining, MDA/SOD assays), protein expression of NLRP3, TXNIP, IL-1β, and IL-18 via Western blot, and neuronal apoptosis by TUNEL staining.

Results: In vitro, Rd dose-dependently suppressed LPS-induced expression of IL-1β, IL-6, TNF-α and M1 markers in microglia/macrophages. Transcriptomics and biochemical assays demonstrated that Rd attenuated oxidative/ER stress, reduced TXNIP expression and cytosolic translocation, and inhibited NLRP3 inflammasome assembly and caspase-1 activation. In the rat decompression model, Rd treatment (20 mg/kg) significantly improved motor recovery (BBB scores, rotarod, open field), reduced neuronal apoptosis (TUNEL, cleaved caspase-3), and suppressed microglial activation along with IL-1β/IL-18 levels in spinal cord tissue. Rd also lowered MDA and enhanced SOD activity, confirming its antioxidative role.

Conclusions: Ginsenoside Rd effectively mitigates post‑decompression neuroinflammation and promotes functional recovery by targeting the ROS/TXNIP/NLRP3 axis, a key pathway in neuropathic pain development. Its dual modulation of oxidative/ER stress and inflammasome activation attenuates neuronal apoptosis and microglial‑driven inflammation, underscoring Rd as a promising multi‑target agent for preventing chronic postsurgical pain and improving neurological outcomes after spinal surgery.

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Presenting Author: Jia-xuan Zhang
Submitting Author: 张 嘉轩

Senior Author: Min Yao

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Yi-xuan Wang: Ph.D. - Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
• Jia-xuan Zhang: M.Med. - Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
• Zhuo-yao Li: M.Med. - Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China