Department of Pharmaceutical Sciences, University of Calabria, I-87036 Rende (CS), Italy.
Curr Med Chem. 2011;18(8):1137-45. doi: 10.2174/092986711795029690.
Nitric oxide (NO) is a diatomic free radical produced from L-arginine by constitutive and inducible nitric oxide synthase (cNOS and iNOS) in numerous mammalian cells and tissues. Nitric oxide (NO), superoxide (O2-) and their reaction product peroxynitrite (ONOO-) may be generated in excess during the host response against viral and antibacterial infections and contribute to some pathogenesis by promoting oxidative stress, tissue injury and, even, cancer. Oxidative damage, caused by action of free radicals, may initiate and promote the progression of a number of chronic diseases, including cancer, cardiovascular diseases, Alzheimer's disease, diabetes and inflammation. The mechanism of inflammation injury is attributed, in part, to release of reactive oxygen species from activated neutrophils and macrophages. ROS propagate inflammation by stimulating release of mediators such as NO and cytokines. The interest of the research is motivated by the current need to find new substances of natural origin which have demonstrated effectiveness in the described fields of application and low degree of toxicity for humans. Natural products provide a vast pool of NO inhibitors that can possibly be developed into clinical products. This article reviews some plenolic secondary metabolites from plants with NO inhibitory properties and their structure-activity relationship studies that can be focused for drug development programs.
一氧化氮(NO)是一种双原子自由基,由组成型和诱导型一氧化氮合酶(cNOS 和 iNOS)在许多哺乳动物细胞和组织中从 L-精氨酸产生。在宿主对抗病毒和细菌感染的反应中,一氧化氮(NO)、超氧化物(O2-)及其反应产物过氧亚硝酸盐(ONOO-)可能会过量产生,并通过促进氧化应激、组织损伤甚至癌症而导致一些发病机制。自由基作用引起的氧化损伤可能引发和促进许多慢性疾病的进展,包括癌症、心血管疾病、阿尔茨海默病、糖尿病和炎症。炎症损伤的机制部分归因于激活的中性粒细胞和巨噬细胞中活性氧物质的释放。ROS 通过刺激如 NO 和细胞因子等介质的释放来引发炎症。研究的兴趣源于目前寻找具有以下特性的天然来源新物质的需要:在所述应用领域证明有效,且对人体的毒性低。天然产物提供了大量具有 NO 抑制特性的多酚类次生代谢物,这些代谢物可能被开发成临床产品。本文综述了一些具有 NO 抑制特性的植物来源的多酚类次生代谢物及其结构-活性关系研究,这些研究可能成为药物开发计划的重点。