IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.
CNS Neurol Disord Drug Targets. 2011 Nov;10(7):849-62. doi: 10.2174/187152711798072310.
Neurodegenerative diseases are a group of chronic, progressive disorders characterized by the gradual loss of neurons in several areas of the central nervous system (CNS). Substantial evidence has documented a common inflammatory mechanism in neurodegeneration. It is known that classical anti-inflammatory agents, steroids and nonsteroidal anti-inflammatory drugs, have not played a major role in the management of CNS inflammatory conditions. This may be partly due to the natural compartmentation of the brain by the blood-brain barrier. Thus, there is much interest in developing novel anti-inflammatory drugs that may help to prevent or ameliorate CNS inflammation. Resveratrol (RSV) has received considerable attention over the last several decades. Experimental studies have revealed its benefits in several human disease models, including cardio- and neuro-protection, immune regulation and cancer chemoprevention. The broad action spectrum of RSV is explained by the involvement of numerous signaling networks and cellular effector mechanisms. Among them, apoptotic and antioxidant targets have been implicated. Recently, also anti-neuroinflammatory activity has been observed. A number of studies demonstrated that RSV mediates the downregulation of various inflammatory biomarkers such as tumor necrosis factor, cyclooxygenase 2, inducible nitric oxide synthase and interleukins. This activity seems to depend on some structural features of RSV such as the number and the position of hydroxyl groups. In this review, a comprehensive account of multiple intracellular RSV targets involved in neuroinflammation and its analogues design will be treated, pointing to structure/activity relationships.
神经退行性疾病是一组慢性、进行性疾病，其特征是中枢神经系统 (CNS) 多个区域的神经元逐渐丧失。大量证据记录了神经退行性变中的共同炎症机制。众所周知，经典的抗炎药、类固醇和非甾体抗炎药在 CNS 炎症疾病的治疗中并没有发挥主要作用。这可能部分归因于血脑屏障对大脑的天然分隔。因此，人们对开发新型抗炎药物很感兴趣，这些药物可能有助于预防或改善 CNS 炎症。白藜芦醇 (RSV) 在过去几十年中受到了相当多的关注。实验研究表明，它在几种人类疾病模型中都有好处，包括心脏和神经保护、免疫调节和癌症化学预防。RSV 的广泛作用谱是由涉及众多信号网络和细胞效应机制来解释的。其中，凋亡和抗氧化靶点已被牵涉其中。最近，也观察到了抗神经炎症活性。许多研究表明，RSV 介导了多种炎症生物标志物（如肿瘤坏死因子、环氧化酶 2、诱导型一氧化氮合酶和白细胞介素）的下调。这种活性似乎取决于 RSV 的一些结构特征，如羟基的数量和位置。在这篇综述中，将对涉及神经炎症的 RSV 多种细胞内靶标及其类似物的设计进行全面论述，指出结构/活性关系。
