Synergistic Effect of L-Carnosine and EGCG in the Prevention of Physiological Brain Aging

Synergistic Effect of L-Carnosine and EGCG in the Prevention of Physiological Brain Aging
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DOI:
10.2174/1381612811319150007
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发表时间:
2013-05-01
影响因子:
3.1
通讯作者:
Scapagnini, Giovanni
Scapagnini, Giovanni
中科院分区:
医学4区
文献类型:
--
作者:
Davinelli, Sergio;Di Marco, Roberto;Scapagnini, Giovanni

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多靶点作用的益处在各种病理模型中得到了很好的证实。许多膳食补充剂和营养保健品可能有助于减缓与年龄相关的认知能力下降和发展神经退行性疾病的风险。l -肌肽和EGCG是受到特别关注的天然化合物,因为它们在调节与衰老和慢性疾病相关的氧化应激方面具有潜在作用。这些天然物质的生物活性经常被用来预防或减少衰老特征;然而,它们从未被评估为联合治疗。在本研究中,我们研究了l -肌肽和EGCG对HO-1和Hsp72 (Hsp70的诱导形式)两种应激反应通路激活的联合作用,这两种通路在氧化应激诱导的细胞损伤中起重要的细胞保护作用。我们证明EGCG和l -肌肽的神经保护作用是通过调节HO-1/Hsp72系统实现的。此外,这两种化合物的联合作用导致HO-1表达的协同增加,这表明HO-1与hsp72介导的途径之间存在串扰。我们的研究结果表明,EGCG和l -肌肽联合给药可以通过减少氧化应激引起的神经元损伤而有利于神经退行性疾病的治疗和预防。
The benefits of multi-target action are well established in a variety of pathological models. Many dietary supplements and nutraceuticals may be useful to slow age-related cognitive declines and the risk of developing neurodegenerative disease. L-Carnosine and EGCG are natural compounds that have received particular attention because of their potential role in modulating oxidative stress associated with aging and chronic conditions. The biological activities of these naturally occurring substances have frequently been used to prevent or reduce senile features; however they have never been evaluated as a combined treatment. In the present study we investigated the combined effect of L-Carnosine and EGCG on the activation of two stress-responsive pathways: HO-1 and Hsp72 (the inducible form of Hsp70), which play an important role in cytoprotection against oxidative stress-induced cell damage. We demonstrated that the neuroprotective effects of EGCG and L-Carnosine are achieved through the modulation of HO-1/Hsp72 systems. Furthermore, the combined action of both compounds resulted in a synergistic increase of HO-1 expression which suggests a crosstalk between the HO-1 and the Hsp72-mediated pathways. Our results indicate that the combined administration of EGCG and L-Carnosine would benefit the treatment and prevention of neurodegenerative diseases by reducing the neuronal damage caused by oxidative stress.