Hyperoside Alleviates Macrophage-mediated Neuroinflammation And Oxidative Stress Through Activating PI3K/AKT And Nrf2/HO-1 Signaling Pathway Post Spinal Cord Injury

Abstract

Abstract Background Spinal cord injury (SCI) is a troublesome and destructive disease in the central nervous system (CNS) that leads to severe sensory and locomotor damage. Neuro-inflammation and oxidative stress are secondary injuries after SCI, and treating SCI to with the anti-inflammatory and antioxidant drug is an effective treatment method. Hyperoside (HYP), a Chinese medicinal herb, has been demonstrated to have anti-inflammmation and anti-oxidative pharmacological effects. Objective In order to explore whether HYP can alleviate the secondary injury and promote the recovery of motor function after SCI. Methods Neuro-inflammation and oxidative stress were detected by western blotting (WB), immunofluorescence (IF) staining, and Real-time quantitative reverse-transcription PCR (qRT-PCR) both in vitro and in vivo. HYP (10 mg/kg, 50 mg/kg) were intraperitoneally injected into SCI mice in vivo. Basso mouse scale scores and swimming test were performed to evaluate locomotor function recovery of SCI mice. Morphology were assessed by Hematoxylin-eosin, Nissl, and Luxol Fast Blue staining following SCI. Results HYP decreased the level of pro-inflammatory mediators (IL-1β, IL-6, TNF-α, iNOS and COX-2) and oxidative stress-related indicators (NOX1, NOX2 and NOX4). Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) expression were increased by treating with HYP. Additionally, HYP upregulated transcription factor nuclear factor E2-related factor 2 (Nrf2) and Heme oxygenase 1 (HO-1). HYP administration decreased tissue deficiency, alleviated demyelination, protected neural structure and function, and promoted locomotor recovery post SCI. Conclusion HYP mitigated macrophage-mediated neuroinflammation and oxidative stress by activating the PI3K/AKT and Nrf2/HO-1 signaling pathway post SCI. This research revealed that HYP contributed a neuroprotective effect to reduce nervous tissue damage and promoting locomotor recovery after SCI.