Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Spinal cord injury (SCI) is a severe condition causing sensory, motor, and autonomic dysfunctions, with over 759,000 patients and 66,374 new cases yearly in China. Secondary injury, driven by inflammation and apoptosis, hinders neurorestoration, making treatment challenging. Schisantherin B (SCHB), an active component of the traditional Chinese medicine Schisandra chinensis, has anti-inflammatory and anti-apoptotic effects in cerebrovascular and neurodegenerative diseases but its role in SCI remains unstudied. Objectives: This study aimed to investigate SCHB’s therapeutic effects on SCI and clarify its underlying molecular mechanism, focusing on the PI3K/AKT signaling pathway. Methods: In vitro, H2O2-induced PC12 cell apoptosis models were treated with different SCHB concentrations; cell viability (microplate reader), apoptosis (flow cytometry, immunofluorescence for cleaved caspase-3), and PI3K/AKT activation (immunofluorescence) were detected. In vivo, mouse SCI models (12.5g weight-drop contusion) received 15mg/kg SCHB intravenously; motor function (Basso Mouse Scale, footprint analysis), tissue damage (HE/Nissl staining), apoptosis (TUNEL staining), inflammation (ELISA for TNF-?/IL-1?/IL-6/IL-10), and PI3K/AKT activation (Western blot, immunofluorescence) were assessed. Results: SCHB (25?M in vitro) increased PC12 cell viability (66.15% vs. 40.86% in H2O2 group), reduced apoptosis (5.84% vs. 10.81%), and upregulated PI3K/AKT proteins. In mice, SCHB improved BMS scores (21/28 days post-injury), increased stride length/width, reduced spinal cord cavity size, preserved motor neurons, lowered pro-inflammatory cytokines (TNF-?/IL-1?/IL-6), elevated IL-10, and activated the PI3K/AKT pathway. Conclusion: SCHB exerts therapeutic effects on SCI by inhibiting inflammation and apoptosis via activating the PI3K/AKT signaling pathway, supporting its potential as a candidate for SCI treatment.