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Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury？

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Neural Regeneration Research 2018年第1期13卷 119-127页

作者： 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 Institute of Experimental Medicine Academy of Sciences of the Czech Republic Videfiska Prague Czech Republic Department of Neuroscience Charles University Second Faculty of Medicine Prague Czech Republic New York Medical College Valhalla NY USA

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 mmunohistochemistry （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.

关键词： spinal cord injury epigallocatechin gallate curcumin inflammatory response neural regeneration

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