Buyang Huanwu Decoction inhibits neuronal ferroptosis induced by ischemic stroke in rats
DOI:
https://doi.org/10.66238/fsrma119Keywords:
Ischemic stroke, Ferroptosis, Iron metabolism, TFR1/DMT1, Buyang Huanwu DecoctionAbstract
Objective: To investigate the regulatory mechanism of the ferroptosis signaling pathway in ischemic cerebral neurons and evaluate the intervention effect of Buyang Huanwu Decoction (BYHWD).
Methods: Sixty male Sprague-Dawley rats were randomly assigned to four groups: sham, ischemic stroke (IS), IS+DFP (deferiprone), and IS+BYHWD group. After a 5-day acclimatization period, drug administration commenced. The middle cerebral artery occlusion (MCAO) model was established via the intraluminal suture method. Neurological deficits were assessed using the Longa score at 2 h post-operation. Protein expression levels of TFR1 and DMT1 were semi-quantitatively detected by Western blot. Ferroptosis-related indicators in the ischemic brain were evaluated: brain iron deposition, malondialdehyde (MDA), and glutathione (GSH) levels were measured using assay kits, and reactive oxygen species (ROS) levels were determined by luminol-based chemiluminescence.
Results: Compared with the sham group, the IS group exhibited significantly increased neurological deficit scores (P< 0.01) and up-regulated TFR1 and DMT1 protein expression (P< 0.01). Brain iron deposition, MDA, and ROS levels were elevated, while GSH content was decreased (P< 0.05). Compared with the IS group, the IS+BYHWD group showed significantly alleviated neurological deficits (P< 0.01), down-regulated TFR1 and DMT1 expression (P< 0.01), reduced brain iron deposition, MDA, and ROS levels, and increased GSH content (P< 0.05).
Conclusion: BYHWD confers an anti-ferroptotic effect on acute cerebral ischemic neurons via regulation of the TFR1/DMT1 signaling pathway, resulting in decreased iron deposition, lipid peroxidation, and ROS accumulation in the ischemic brain, and ultimately improving neurological outcomes in IS rats.
References
Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic
analysis for the Global Burden of Disease Study 2019. Lancet Neurol, 2021. 20(10): p. 795–820.
Xie, Y., et al., Ferroptosis: process and function. Cell death and differentiation, 2016. 23(3): p.
369–379.
Dixon, S.J., et al., Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell, 2012.
149(5): p. 1060–72.
Wang, R., et al., Efficacy evaluation of Buyang Huanwu Decoction in the treatment of ischemic
stroke in the recovery period: A systematic review of randomized controlled trials. Front
Pharmacol, 2022. 13: p. 975816.
Huang, H., et al., Buyang Huanwu Decoction Alleviates Ischemic Stroke Injury by Inhibiting
Ferroptosis via the Nrf2/GPX4 Pathway. Drug Des Devel Ther, 2025. 19: p. 2285–2305.
Longa, E.Z., et al., Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 1989. 20(1): p. 84–91.
Li, H., et al., The pharmacokinetics effects of the MCAO model on senkyunolide I in pseudo
germ-free rats after oral co-administration of Chuanxiong and warfarin. Front Pharmacol,
2025. 16: p. 1577757.
Fish, W.W., Rapid colorimetric micromethod for the quantitation of complexed iron in biological
samples. Methods Enzymol, 1988. 158: p. 357–64.
Li H , Li F , Zhou Y ,et al.The pharmacokinetics effects of the MCAO model on senkyunolide I in
pseudo germ-free rats after oral co-administration of Chuanxiong and warfarin[J].Frontiers in Pharmacology, 2025.
Chen, L., et al., Homeostasis and metabolism of iron and other metal ions in neurodegenerative
diseases. Signal Transduct Target Ther, 2025. 10(1): p. 31.
Zhong, D.Y., et al., Systematic evaluation and re-evaluation of buyang huanwu decoction in
treating ischemic stroke. Complement Ther Med, 2022. 70: p. 102860.
Zhu, T., et al., Therapeutic targets of neuroprotection and neurorestoration in ischemic stroke:
Applications for natural compounds from medicinal herbs. Biomed Pharmacother, 2022.
148: p. 112719.
Yin, Y.Y., F.F. Zhu, and G.C. Wu, [Protective effect of astragalosides on anoxia/reoxygenation
injury of hippocampal neuron]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2010. 30(11): p.
1173–7.
Tian, X.R., et al., Astragaloside IV Pretreatment Alleviates Pulmonary Ischemia-Reperfusion
Injury via the TLR4/MyD88/NF-κB p65 Pathway in Rats. Phytother Res, 2025. 39(10): p.
4744–4765.
Feng, X.F., et al., Tetramethylpyrazine promotes stroke recovery by inducing the restoration of
neurovascular unit and transformation of A1/A2 reactive astrocytes. Front Cell Neurosci,
2023. 17: p. 1125412.
Wang, Y.H., et al., Lumbrokinase regulates endoplasmic reticulum stress to improve neurological
deficits in ischemic stroke. Neuropharmacology, 2022. 221: p. 109277
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