Buyang Huanwu Decoction Multi-target Synergistic Inhibition of Ferroptosis After Spinal Cord Injury via the Nrf2/HO-1 Signaling Pathway:Mechanism of Action
GUO Xiaohui
BU Baoxian
QIAN Yuhao
LI Yanxia
BU Xianzhong
LI Hanxi
HAO Yupeng
Abstract：Objective To investigate the mechanism of action by which Buyang Huanwu Decoction mediates multi-target inhibition of ferroptosis in rats after spinal cord injury(SCI)based on the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods Forty-eight Sprague-Dawley rats were randomly divided into a sham group,a model group,a control group,and an observation group.After successful model establishment,rats in the control group received intraperitoneal injection of sulforaphane,while rats in the observation group were administered Buyang Huanwu Decoction via intragastric gavage.At 3 days(3 d)and 7 days(7 d)post-modeling,Basso-Beattie-Bresnahan(BBB)locomotor scoring was performed on all groups,followed by tissue collection.Hematoxylin and eosin(HE)staining was used to observe morphological changes in spinal cord neuronal tissue.Total iron ion content and glutathione peroxidase 4(GPX4)expression were detected by enzyme-linked immunosorbent assay(ELISA).Western blotting was employed to measure the protein expression levels of Nrf2 and HO-1 in the injured spinal cord region.Results In BBB locomotor scoring at 3 d and 7 d post-modeling,the control and observation groups showed higher hindlimb BBB scores compared to the model group(P＜0.001).At both 3 d and 7 d,the iron ion content in the control and observation groups was lower than in the model group(P＜0.001),while GPX4 content in the injured spinal cord region was higher(P＜0.001).At 7 d post-modeling,the protein expression levels of Nrf2 and HO-1 in the control and observation groups were upregulated compared to the model group(P＜0.001).Conclusion Buyang Huanwu Decoction likely inhibits ferroptosis post-SCI through multi-target synergistic regulation,with the core mechanism involving activation of the Nrf2/HO-1 pathway:(1)Reducing iron ion concentration in the injured area to inhibit the Fenton reaction and reactive oxygen species generation;(2)Upregulating GPX4 expression to suppress lipid peroxidation;(3)Promoting Nrf2 nuclear translocation and synergistically inducing HO-1 and other factors to establish an antioxidant defense network.This"iron metabolism-antioxidant-cytoprotection"cascade regulation forms the molecular basis for its improvement of neurological function(BBB score).
Keywords：spinal cord injuryBuyang Huanwu Decoctionferroptosisiron ions
Publication Date：2026-03-28
Online Publishing Date：2026-09-12(First online date of this platform, not the publication date of the document)
Pages：6( 976-981 )