Salidroside ameliorates experimental autoimmune neuritis by dually modulating neuroinflammation and immune homeostasis via PI3K/AKT signaling
- Neurotherapeutics. 2025 Nov 7:e00769. doi: 10.1016/j.neurot.2025.e00769.
- 1. First Clinical Medical College, Ningxia Medical University, Yinchuan, 750004, China.
- 2. Department of Neurology, Tangdu Hospital, Air Force Military Medical University, Xi'an, 710038, China.
- 3. NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing, 400016, China; The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: [email protected].
- 4. Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, 750004, China; Diagnosis and Treatment Engineering Technology Research Center of Nervous System Diseases of Ningxia Hui Autonomous Region, Yinchuan, 750004, China; Neurology Center, General Hospital of Ningxia Medical University, Yinchuan, 750004, China. Electronic address: [email protected].
Guillain-Barré syndrome (GBS), an acute autoimmune peripheral neuritis, remains a clinical challenge due to limited therapeutic efficacy and heterogeneous patient responses. The present study investigated salidroside (SAL), a bioactive phenylethanoid glycoside derived from Rhodiola rosea, for its dual anti-inflammatory and neuroprotective properties using experimental autoimmune neuritis (EAN), a validated GBS model. Integrated network pharmacology and molecular docking analyses identified PI3K/Akt signaling as the principal mechanistic target of SAL. In vivo administration of SAL (100 mg/kg/day, intragastric) significantly reduced neurological deficits, alleviated histopathological damage in sciatic nerves, and restored Th1/Th17-Treg immune balance in EAN rats. Mechanistic analysis demonstrated that SAL inhibited NF-κB activation through inhibition of IκBα degradation and p65 nuclear translocation, leading to downregulation of pro-inflammatory cytokines (TNF-α). Concurrently, SAL promoted macrophage polarization from the pro-inflammatory M1 (CD86+) to anti-inflammatory M2 (CD206+) phenotypes. The findings indicate that SAL mitigates EAN through a dual mechanism involving suppression of NF-κB-mediated neuroinflammation and immunomodulation via macrophage phenotype remodeling. The results further establish the PI3K/Akt pathway as a pharmacologically tractable target in autoimmune neuropathies and provide mechanistic evidence supporting SAL as a multi-target immunomodulatory candidate for GBS therapy.