Bu Shen Huo Xue Formula Provides Neuroprotection Against Spinal Cord Injury by Inhibiting Oxidative Stress by Activating the Nrf2 Signaling Pathway

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2024 Nov 4

PMID 39494153

Authors

Dan Luo

Yonghui Hou

Jiheng Zhan

Yu Hou

Zenglu Wang

Xing Li

Lili Sui

Shudong Chen

Dingkun Lin

Affiliations

Soon will be listed here.

Abstract

Purpose: Spinal cord injury (SCI) is an irreversible neurological disease that can result in severe neurological dysfunction. The Bu Shen Huo Xue Formula (BSHXF) has been clinically shown to assist in the recovery of limb function in patients with SCI. However, the underlying mechanisms of BSHXF's therapeutic effects remain unclear. This study aimed to evaluate the effects of BSHXF in a mouse model of SCI and to identify potential therapeutic targets.

Methods: The composition of BSHXF was analyzed using high-performance liquid chromatography (HPLC). In vivo, SCI was induced in mice following established protocols, followed by administration of BSHXF. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB) and footprint tests. Levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were quantified with specific assay kits. Protein expression analysis was performed using Western blot and immunofluorescence. Additionally, reactive oxygen species (ROS) levels and apoptosis rates were evaluated with dedicated staining kits. In vitro, neurons were exposed to lipopolysaccharide (LPS) to investigate the effects of BSHXF on neuronal oxidative stress. The protective effects of BSHXF against LPS-induced neuronal injury were examined through RT-PCR, Western blot, and immunofluorescence.

Results: The eight primary bioactive constituents of BSHXF were identified using HPLC. BSHXF significantly reduced tissue damage and enhanced functional recovery following SCI. Meanwhile, BSHXF treatment led to significant reductions in oxidative stress and apoptosis rates. It also reversed neuronal loss and reduced glial scarring after SCI. LPS exposure induced neuronal apoptosis and axonal degeneration; however, after intervention with BSHXF, neuronal damage was reduced, and the protective effects of BSHXF were mediated by the activation of the Nrf2 pathway.

Conclusion: BSHXF decreased tissue damage and enhanced functional recovery after SCI by protecting neurons against oxidative stress and apoptosis. The effects of BSHXF on SCI may be related to the activation of the Nrf2 pathway.

References

Palumbo M, Moroni A, Quiroga S, Castro M, Burgueno A, Genaro A . Immunomodulation induced by central nervous system-related peptides as a therapeutic strategy for neurodegenerative disorders. Pharmacol Res Perspect. 2021; 9(5):e00795. PMC: 8491457. DOI: 10.1002/prp2.795. View

Ma D, Zhang N, Zhang Y, Chen H . Salvianolic Acids for Injection alleviates cerebral ischemia/reperfusion injury by switching M1/M2 phenotypes and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia in vivo and in vitro. J Ethnopharmacol. 2021; 270:113776. DOI: 10.1016/j.jep.2021.113776. View

Li J, Luo W, Xiao C, Zhao J, Xiang C, Liu W . Recent advances in endogenous neural stem/progenitor cell manipulation for spinal cord injury repair. Theranostics. 2023; 13(12):3966-3987. PMC: 10405838. DOI: 10.7150/thno.84133. View

Liu X, Zhang Y, Wang Y, Qian T . Inflammatory Response to Spinal Cord Injury and Its Treatment. World Neurosurg. 2021; 155:19-31. DOI: 10.1016/j.wneu.2021.07.148. View

Rodrigues L, Moura-Neto V, Spohr T . Biomarkers in Spinal Cord Injury: from Prognosis to Treatment. Mol Neurobiol. 2018; 55(8):6436-6448. DOI: 10.1007/s12035-017-0858-y. View

Chen S, Tian R, Luo D, Xiao Z, Li H, Lin D . Time-Course Changes and Role of Autophagy in Primary Spinal Motor Neurons Subjected to Oxygen-Glucose Deprivation: Insights Into Autophagy Changes in a Cellular Model of Spinal Cord Ischemia. Front Cell Neurosci. 2020; 14:38. PMC: 7098962. DOI: 10.3389/fncel.2020.00038. View

Wang S, Hong S, Tan J . Five Different Lives after Suffering from Spinal Cord Injury: The Experiences of Nurses Who Take Care of Spinal Cord Injury Patients. Int J Environ Res Public Health. 2022; 19(3). PMC: 8834452. DOI: 10.3390/ijerph19031058. View

Wang X, Feng S, Wang Y, Chen N, Wang Z, Zhang Y . Paeoniflorin: A neuroprotective monoterpenoid glycoside with promising anti-depressive properties. Phytomedicine. 2021; 90:153669. DOI: 10.1016/j.phymed.2021.153669. View

Hu X, Xu W, Ren Y, Wang Z, He X, Huang R . Spinal cord injury: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2023; 8(1):245. PMC: 10291001. DOI: 10.1038/s41392-023-01477-6. View

10.

Quadri S, Farooqui M, Ikram A, Zafar A, Khan M, Suriya S . Recent update on basic mechanisms of spinal cord injury. Neurosurg Rev. 2018; 43(2):425-441. DOI: 10.1007/s10143-018-1008-3. View

11.

. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019; 18(5):459-480. PMC: 6459001. DOI: 10.1016/S1474-4422(18)30499-X. View

12.

Tian T, Zhang S, Yang M . Recent progress and challenges in the treatment of spinal cord injury. Protein Cell. 2023; 14(9):635-652. PMC: 10501188. DOI: 10.1093/procel/pwad003. View

13.

Hosseini S, Borys B, Karimi-Abdolrezaee S . Neural stem cell therapies for spinal cord injury repair: an update on recent preclinical and clinical advances. Brain. 2023; 147(3):766-793. DOI: 10.1093/brain/awad392. View

14.

Xiao Z, Liu W, Mu Y, Zhang H, Wang X, Zhao C . Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage. Front Pharmacol. 2020; 11:572373. PMC: 7741185. DOI: 10.3389/fphar.2020.572373. View

15.

Hou Y, Luo D, Hou Y, Luan J, Zhan J, Chen Z . Bu Shen Huo Xue decoction promotes functional recovery in spinal cord injury mice by improving the microenvironment to promote axonal regeneration. Chin Med. 2022; 17(1):85. PMC: 9277908. DOI: 10.1186/s13020-022-00639-y. View

16.

Heitman E, Ingram D . Cognitive and neuroprotective effects of chlorogenic acid. Nutr Neurosci. 2014; 20(1):32-39. DOI: 10.1179/1476830514Y.0000000146. View

17.

Zhang H, Wang J, Wang Y, Gao C, Gu Y, Huang J . Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the Akt/GSK-3/Nrf2 Signaling Pathway and Inhibiting the NF-B Signaling Pathway in 5/6 Nephrectomized Rats. Oxid Med Cell Longev. 2019; 2019:2853534. PMC: 6442489. DOI: 10.1155/2019/2853534. View

18.

Chen J, Shen Y, Shao X, Wu W . An emerging role of inflammasomes in spinal cord injury and spinal cord tumor. Front Immunol. 2023; 14:1119591. PMC: 10033975. DOI: 10.3389/fimmu.2023.1119591. View

19.

Sun Z, Yang L, Zhao L, Cui R, Yang W . Neuropharmacological Effects of Mesaconitine: Evidence from Molecular and Cellular Basis of Neural Circuit. Neural Plast. 2020; 2020:8814531. PMC: 7456483. DOI: 10.1155/2020/8814531. View

20.

Lv R, Du L, Zhang L, Zhang Z . Polydatin attenuates spinal cord injury in rats by inhibiting oxidative stress and microglia apoptosis via Nrf2/HO-1 pathway. Life Sci. 2018; 217:119-127. DOI: 10.1016/j.lfs.2018.11.053. View