Does Combined Therapy of Curcumin and Epigallocatechin Gallate Have a Synergistic Neuroprotective Effect Against Spinal Cord Injury?

Overview

Journal Neural Regen Res

Date 2018 Feb 17

PMID 29451216

Citations 16

Authors

Jiri Ruzicka

Lucia Machova Urdzikova

Barbora Svobodova

Anubhav G Amin

Kristyna Karova

Jana Dubisova

Kristyna Zaviskova

Sarka Kubinova

Meic Schmidt

Meena Jhanwar-Uniyal

Pavla Jendelova

Affiliations

Soon will be listed here.

Abstract

Systematic inflammatory response after spinal cord injury (SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test, flat beam test). Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining) and immunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43). Cytokine levels (interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf) related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.

Citing Articles

Therapeutic potential of flavonoids in neuroprotection: brain and spinal cord injury focus.

Faysal M, Al Amin M, Zehravi M, Sweilam S, Arjun U, Gupta J Naunyn Schmiedebergs Arch Pharmacol. 2025; .

PMID: 40014123 DOI: 10.1007/s00210-025-03888-4.

Mechanistic insight of curcumin: a potential pharmacological candidate for epilepsy.

Khatoon S, Kalam N Front Pharmacol. 2025; 15():1531288.

PMID: 39845785 PMC: 11752882. DOI: 10.3389/fphar.2024.1531288.

Epigallocatechin 3-gallate-induced neuroprotection in neurodegenerative diseases: molecular mechanisms and clinical insights.

Islam M, Rauf A, Akter S, Akter H, Al-Imran M, Islam S Mol Cell Biochem. 2025; .

PMID: 39832108 DOI: 10.1007/s11010-025-05211-4.

Curcumin/pEGCG-encapsulated nanoparticles enhance spinal cord injury recovery by regulating CD74 to alleviate oxidative stress and inflammation.

Chen T, Wan L, Xiao Y, Wang K, Wu P, Li C J Nanobiotechnology. 2024; 22(1):653.

PMID: 39443923 PMC: 11515499. DOI: 10.1186/s12951-024-02916-4.

Combinatorial therapies for spinal cord injury repair.

Sousa C, Monteiro A, Salgado A, Silva N Neural Regen Res. 2024; 20(5):1293-1308.

PMID: 38845223 PMC: 11624878. DOI: 10.4103/NRR.NRR-D-24-00061.

References

Renno W, Al-Maghrebi M, Rao M, Khraishah H . (-)-Epigallocatechin-3-gallate modulates spinal cord neuronal degeneration by enhancing growth-associated protein 43, B-cell lymphoma 2, and decreasing B-cell lymphoma 2-associated x protein expression after sciatic nerve crush injury. J Neurotrauma. 2014; 32(3):170-84. PMC: 4298756. DOI: 10.1089/neu.2014.3491. View

Hoppe J, Coradini K, Frozza R, Oliveira C, Meneghetti A, Bernardi A . Free and nanoencapsulated curcumin suppress β-amyloid-induced cognitive impairments in rats: involvement of BDNF and Akt/GSK-3β signaling pathway. Neurobiol Learn Mem. 2013; 106:134-44. DOI: 10.1016/j.nlm.2013.08.001. View

Metin Sanli A, Turkoglu E, Serbes G, Sargon M, Besalti O, Kilinc K . Effect of curcumin on lipid peroxidation, early ultrastructural findings and neurological recovery after experimental spinal cord contusion injury in rats. Turk Neurosurg. 2012; 22(2):189-95. DOI: 10.5137/1019-5149.JTN.5193-11.1. View

Gokce E, Kahveci R, Gokce A, Sargon M, Kisa U, Aksoy N . Curcumin Attenuates Inflammation, Oxidative Stress, and Ultrastructural Damage Induced by Spinal Cord Ischemia-Reperfusion Injury in Rats. J Stroke Cerebrovasc Dis. 2016; 25(5):1196-1207. DOI: 10.1016/j.jstrokecerebrovasdis.2016.01.008. View

Khalatbary A, Ahmadvand H . Anti-inflammatory effect of the epigallocatechin gallate following spinal cord trauma in rat. Iran Biomed J. 2011; 15(1-2):31-7. PMC: 3639740. View

Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D . Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci. 2005; 25(38):8807-14. PMC: 6725500. DOI: 10.1523/JNEUROSCI.1521-05.2005. View

Son S, Kim K, Cho D, Kim H, Sung J, Bae J . Curcumin Stimulates Proliferation of Spinal Cord Neural Progenitor Cells via a Mitogen-Activated Protein Kinase Signaling Pathway. J Korean Neurosurg Soc. 2014; 56(1):1-4. PMC: 4185312. DOI: 10.3340/jkns.2014.56.1.1. View

Liu W, Xu Z, Li H, Guo M, Yang T, Feng S . Protective effects of curcumin against mercury-induced hepatic injuries in rats, involvement of oxidative stress antagonism, and Nrf2-ARE pathway activation. Hum Exp Toxicol. 2016; 36(9):949-966. DOI: 10.1177/0960327116677355. View

Alvarez-Perez B, Homs J, Bosch-Mola M, Puig T, Reina F, Verdu E . Epigallocatechin-3-gallate treatment reduces thermal hyperalgesia after spinal cord injury by down-regulating RhoA expression in mice. Eur J Pain. 2015; 20(3):341-52. DOI: 10.1002/ejp.722. View

10.

Heid C, Stevens J, Livak K, Williams P . Real time quantitative PCR. Genome Res. 1996; 6(10):986-94. DOI: 10.1101/gr.6.10.986. View

11.

Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott A . T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. Leukemia. 2005; 19(4):652-8. DOI: 10.1038/sj.leu.2403644. View

12.

Machova Urdzikova L, Karova K, Ruzicka J, Kloudova A, Shannon C, Dubisova J . The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation. Int J Mol Sci. 2016; 17(1). PMC: 4730294. DOI: 10.3390/ijms17010049. View

13.

Zhu H, Bian C, Yuan J, Chu W, Xiang X, Chen F . Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury. J Neuroinflammation. 2014; 11:59. PMC: 3986937. DOI: 10.1186/1742-2094-11-59. View

14.

Bibikova M, Yeakley J, Chudin E, Chen J, Wickham E, Wang-Rodriguez J . Gene expression profiles in formalin-fixed, paraffin-embedded tissues obtained with a novel assay for microarray analysis. Clin Chem. 2004; 50(12):2384-6. DOI: 10.1373/clinchem.2004.037432. View

15.

Urdzikova L, Jendelova P, Glogarova K, Burian M, Hajek M, Sykova E . Transplantation of bone marrow stem cells as well as mobilization by granulocyte-colony stimulating factor promotes recovery after spinal cord injury in rats. J Neurotrauma. 2006; 23(9):1379-91. DOI: 10.1089/neu.2006.23.1379. View

16.

Machova Urdzikova L, Ruzicka J, Karova K, Kloudova A, Svobodova B, Amin A . A green tea polyphenol epigallocatechin-3-gallate enhances neuroregeneration after spinal cord injury by altering levels of inflammatory cytokines. Neuropharmacology. 2017; 126:213-223. DOI: 10.1016/j.neuropharm.2017.09.006. View

17.

Renno W, Al-Khaledi G, Mousa A, Karam S, Abul H, Asfar S . (-)-Epigallocatechin-3-gallate (EGCG) modulates neurological function when intravenously infused in acute and, chronically injured spinal cord of adult rats. Neuropharmacology. 2013; 77:100-19. DOI: 10.1016/j.neuropharm.2013.09.013. View

18.

Yang J, Wang C, Zhang Z, Chen X, Jia Y, Wang B . Curcumin inhibits the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway. APMIS. 2017; 125(2):134-140. DOI: 10.1111/apm.12650. View

19.

Yunos N, Beale P, Yu J, Huq F . Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells. Anticancer Res. 2011; 31(4):1131-40. View

20.

Carstens E, Ansley D . Hindlimb flexion withdrawal evoked by noxious heat in conscious rats: magnitude measurement of stimulus-response function, suppression by morphine and habituation. J Neurophysiol. 1993; 70(2):621-9. DOI: 10.1152/jn.1993.70.2.621. View