Gallic Acid Showed Neuroprotection Against Endoplasmic Reticulum Stress in Rats

Overview

Journal Acta Cir Bras

Date 2025 Jan 15

PMID 39813535

Authors

Abdulmutalip Karaaslanli

Mehmet Cudi Tuncer

Firat Asir

Tugcan Korak

Affiliations

Soon will be listed here.

Abstract

Purpose: We aimed to investigate the role of gallic acid treatment on spinal cord tissues after spinal cord injury (SCI) and its relationship with endoplasmic reticulum (ER) stress by histochemical, immunohistochemical, and in-silico techniques.

Methods: Thirty female Wistar albino rats were divided into three groups: sham, SCI, and SCI+gallic acid. SCI was induced by dropping a 15-g weight onto the exposed T10-T11 spinal cord segment. The SCI+gallic acid group received 25 mg/kg of gallic acid intraperitoneally daily for one week. Histopathological, immunohistochemical, and silico analyses were performed.

Results: Histological analysis revealed improved neural cell survival and tissue integrity in the SCI+gallic acid group compared to the SCI group. Caspase-12 expression was significantly increased in the SCI group, indicating elevated ER stress and apoptosis. Gallic acid treatment resulted in a marked reduction in caspase-12 expression in neurons, neuroglia, and endothelial cells, suggesting decreased ER stress.

Conclusion: Gallic acid exhibits significant neuroprotective effects against ER stress and cellular damage in a rat model of SCI. The in-silico analysis revealed apoptotic and immune-related pathways in which gallic acid showed neuroprotective effects by regulating caspase-12. These results suggest that gallic acid may be a promising therapeutic agent for mitigating secondary damage post-SCI.

References

Cao S, Kaufman R . Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease. Antioxid Redox Signal. 2014; 21(3):396-413. PMC: 4076992. DOI: 10.1089/ars.2014.5851. View

Nabavi S, Habtemariam S, Di Lorenzo A, Sureda A, Khanjani S, Nabavi S . Post-Stroke Depression Modulation and in Vivo Antioxidant Activity of Gallic Acid and Its Synthetic Derivatives in a Murine Model System. Nutrients. 2016; 8(5). PMC: 4882661. DOI: 10.3390/nu8050248. View

Xu B, Wang J, Liu S, Liu H, Zhang X, Shi J . HSP70 alleviates spinal cord injury by activating the NF-kB pathway. J Musculoskelet Neuronal Interact. 2021; 21(4):542-549. PMC: 8672413. View

Li Y, Han W, Wu Y, Zhou K, Zheng Z, Wang H . Stabilization of Hypoxia Inducible Factor-1α by Dimethyloxalylglycine Promotes Recovery from Acute Spinal Cord Injury by Inhibiting Neural Apoptosis and Enhancing Axon Regeneration. J Neurotrauma. 2019; 36(24):3394-3409. DOI: 10.1089/neu.2018.6364. View

DeGracia D, Kumar R, Owen C, Krause G, White B . Molecular pathways of protein synthesis inhibition during brain reperfusion: implications for neuronal survival or death. J Cereb Blood Flow Metab. 2002; 22(2):127-41. DOI: 10.1097/00004647-200202000-00001. View

Donovan W . Donald Munro Lecture. Spinal cord injury--past, present, and future. J Spinal Cord Med. 2007; 30(2):85-100. PMC: 2031949. DOI: 10.1080/10790268.2007.11753918. View

Chen X, Shi C, He M, Xiong S, Xia X . Endoplasmic reticulum stress: molecular mechanism and therapeutic targets. Signal Transduct Target Ther. 2023; 8(1):352. PMC: 10502142. DOI: 10.1038/s41392-023-01570-w. View

Springer J, Azbill R, Knapp P . Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury. Nat Med. 1999; 5(8):943-6. DOI: 10.1038/11387. View

Li H, Zhang X, Qi X, Zhu X, Cheng L . Icariin Inhibits Endoplasmic Reticulum Stress-induced Neuronal Apoptosis after Spinal Cord Injury through Modulating the PI3K/AKT Signaling Pathway. Int J Biol Sci. 2019; 15(2):277-286. PMC: 6367543. DOI: 10.7150/ijbs.30348. View

10.

Kahkeshani N, Farzaei F, Fotouhi M, Alavi S, Bahramsoltani R, Naseri R . Pharmacological effects of gallic acid in health and diseases: A mechanistic review. Iran J Basic Med Sci. 2019; 22(3):225-237. PMC: 6528712. DOI: 10.22038/ijbms.2019.32806.7897. View

11.

Kesim D, Asir F, Ayaz H, Korak T . The Effects of Ellagic Acid on Experimental Corrosive Esophageal Burn Injury. Curr Issues Mol Biol. 2024; 46(2):1579-1592. PMC: 10888482. DOI: 10.3390/cimb46020102. View

12.

Perner C, Kruger E . Endoplasmic Reticulum Stress and Its Role in Homeostasis and Immunity of Central and Peripheral Neurons. Front Immunol. 2022; 13:859703. PMC: 9092946. DOI: 10.3389/fimmu.2022.859703. View

13.

Hayashi T, Saito A, Okuno S, Ferrand-Drake M, Dodd R, Chan P . Damage to the endoplasmic reticulum and activation of apoptotic machinery by oxidative stress in ischemic neurons. J Cereb Blood Flow Metab. 2005; 25(1):41-53. DOI: 10.1038/sj.jcbfm.9600005. View

14.

Ayaz H, Asir F, Korak T . Skimmianine Showed Neuroprotection against Cerebral Ischemia/Reperfusion Injury. Curr Issues Mol Biol. 2024; 46(7):7373-7385. PMC: 11276333. DOI: 10.3390/cimb46070437. View

15.

Yin Z, Wan B, Gong G, Yin J . ROS: Executioner of regulating cell death in spinal cord injury. Front Immunol. 2024; 15:1330678. PMC: 10844444. DOI: 10.3389/fimmu.2024.1330678. View

16.

Wilson J, Cadotte D, Fehlings M . Clinical predictors of neurological outcome, functional status, and survival after traumatic spinal cord injury: a systematic review. J Neurosurg Spine. 2012; 17(1 Suppl):11-26. DOI: 10.3171/2012.4.AOSPINE1245. View

17.

Reddy S, La Marca F, Park P . The role of heat shock proteins in spinal cord injury. Neurosurg Focus. 2008; 25(5):E4. DOI: 10.3171/FOC.2008.25.11.E4. View

18.

Lifshutz J, Colohan A . A brief history of therapy for traumatic spinal cord injury. Neurosurg Focus. 2004; 16(1):E5. View

19.

Beere H, Wolf B, Cain K, Mosser D, Mahboubi A, Kuwana T . Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol. 2000; 2(8):469-75. DOI: 10.1038/35019501. View

20.

Obafemi T, Jaiyesimi K, Olomola A, Olasehinde O, Olaoye O, Adewumi F . Combined effect of metformin and gallic acid on inflammation, antioxidant status, endoplasmic reticulum (ER) stress and glucose metabolism in fructose-fed streptozotocin-induced diabetic rats. Toxicol Rep. 2021; 8:1419-1427. PMC: 8319514. DOI: 10.1016/j.toxrep.2021.07.011. View