Machova Urdzikova Lucia, Cimermanova Veronika, Karova Kristyna, Dominguez Jose, Stepankova Katerina, Petrovicova Michaela, Havelikova Katerina, D Gandhi Chirag, Jhanwar-Uniyal Meena, Jendelova Pavla
Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská, 1083 Prague, Czech Republic.
Departments of Neurosurgery, New York Medical College, Valhalla, NY 10595, USA.
Antioxidants (Basel). 2023 Feb 3;12(2):363. doi: 10.3390/antiox12020363.
Spinal cord injury (SCI) is a devastating condition that has physical and psychological consequences for patients. SCI is accompanied by scar formation and systemic inflammatory response leading to an intense degree of functional loss. The catechin, epigallocatechin gallate (EGCG), an active compound found in green tea, holds neuroprotective features and is known for its anti-inflammatory potential. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two functionally distinct complexes termed mTOR complex 1 and 2 (mTORC1; mTORC2). Inhibition of mTORC1 by rapamycin causes neuroprotection, leading to partial recovery from SCI. In this study the effects of EGCG, PP242 (an inhibitor of both complexes of mTOR), and a combination of EGCG and PP242 in SCI have been examined. It has been found that both EGCG and PP242 significantly improved sensory/motor functions following SCI. However, EGCG appeared to be more effective (BBB motor test, from 2 to 8 weeks after SCI, = 0.019, = 0.007, = 0.006, = 0.006, = 0.05, = 0.006, and = 0.003, respectively). The only exception was the Von Frey test, where EGCG was ineffective, while mTOR inhibition by PP242, as well as PP242 in combination with EGCG, significantly reduced withdrawal latency starting from week three (combinatorial therapy (EGCG + PP242) vs. control at 3, 5, and 7 weeks, = 0.011, = 0.007, and = 0.05, respectively). It has been found that EGCG was as effective as PP242 in suppressing mTOR signaling pathways, as evidenced by a reduction in phosphorylated S6 expression (PP242 (-test, < 0.0001) or EGCG (-test, = 0.0002)). These results demonstrate that EGCG and PP242 effectively suppress mTOR pathways, resulting in recovery from SCI in rats, and that EGCG acts via suppressing mTOR pathways.
脊髓损伤（SCI）是一种严重的疾病，会给患者带来生理和心理上的后果。SCI伴随着瘢痕形成和全身炎症反应，导致严重的功能丧失。儿茶素，表没食子儿茶素没食子酸酯（EGCG），一种存在于绿茶中的活性化合物，具有神经保护特性，并以其抗炎潜力而闻名。雷帕霉素的哺乳动物靶点（mTOR）是一种丝氨酸/苏氨酸激酶，存在于两种功能不同的复合物中，称为mTOR复合物1和2（mTORC1；mTORC2）。雷帕霉素抑制mTORC1可导致神经保护，使SCI部分恢复。在本研究中，研究了EGCG、PP242（mTOR两种复合物的抑制剂）以及EGCG和PP242联合使用对SCI的影响。研究发现，EGCG和PP242均能显著改善SCI后的感觉/运动功能。然而，EGCG似乎更有效（BBB运动测试，SCI后2至8周，分别为 = 0.019、 = 0.007、 = 0.006、 = 0.006、 = 0.05、 = 0.006和 = 0.003）。唯一的例外是Von Frey测试，其中EGCG无效，而PP242抑制mTOR以及PP242与EGCG联合使用，从第3周开始显著缩短撤药潜伏期（联合治疗（EGCG + PP242）与对照组在3、5和7周时，分别为 = 0.011、 = 0.oo7和 = 0.05）。研究发现，EGCG在抑制mTOR信号通路方面与PP242一样有效，磷酸化S6表达的降低证明了这一点（PP242（-测试， < 0.0001）或EGCG（-测试， = 0.0002））。这些结果表明，EGCG和PP242有效抑制mTOR通路，导致大鼠SCI恢复，并且EGCG通过抑制mTOR通路发挥作用。
