Jacob Claus
Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, Campus B 2.1, D-66123 Saarbruecken, Germany.
Molecules. 2014 Nov 26;19(12):19588-93. doi: 10.3390/molecules191219588.
During the last decade, research into natural products has experienced a certain renaissance. The urgent need for more and more effective antibiotics in medicine, the demand for ecologically friendly plant protectants in agriculture, "natural" cosmetics and the issue of a sustainable and healthy nutrition in an ageing society have fuelled research into Nature's treasure chest of "green gold". Here, redox active secondary metabolites from plants, fungi, bacteria and other (micro-)organisms often have been at the forefront of the most interesting developments. These agents provide powerful means to interfere with many, probably most cellular signaling pathways in humans, animals and lower organisms, and therefore can be used to protect, i.e., in form of antioxidants, and to frighten off or even kill, i.e., in form of repellants, antibiotics, fungicides and selective, often catalytic "sensor/effector" anticancer agents. Interestingly, whilst natural product research dates back many decades, in some cases even centuries, and compounds such as allicin and various flavonoids have been investigated thoroughly in the past, it has only recently become possible to investigate their precise interactions and mode(s) of action inside living cells. Here, fluorescent staining and labelling on the one side, and appropriate detection, either qualitatively under the microscope or quantitatively in flow cytometers and plate readers, on the other, enable researchers to obtain the various pieces of information necessary to construct a fairly complete puzzle of how such compounds act and interact in living cells. Complemented by the more traditional activity assays and Western Blots, and increasingly joined by techniques such as proteomics, chemogenetic screening and mRNA profiling, these cell based bioanalytical techniques form a powerful platform for "intracellular diagnostics". In the case of redox active compounds, especially of Reactive Sulfur Species (RSS), such techniques have recently unraveled concepts such as the "cellular thiolstat", yet considerably more research is required in order to gain a full understanding of why and how such compounds act-often selectively-in different organisms.
在过去十年中，对天然产物的研究经历了一定程度的复兴。医学上对越来越有效的抗生素的迫切需求、农业中对生态友好型植物保护剂的需求、“天然”化妆品以及老龄化社会中可持续健康营养的问题，推动了对大自然“绿色黄金”宝库的研究。在这里，来自植物、真菌、细菌和其他（微）生物的氧化还原活性次生代谢产物常常处于最有趣进展的前沿。这些物质提供了强大的手段来干扰人类、动物和低等生物中许多（可能是大多数）细胞信号通路，因此可用于保护，即以抗氧化剂的形式，以及驱赶甚至杀死，即以驱虫剂、抗生素、杀菌剂和选择性的、通常是催化性的“传感器/效应器”抗癌剂的形式。有趣的是，虽然天然产物研究可以追溯到几十年前，在某些情况下甚至几个世纪前，并且像大蒜素和各种黄酮类化合物等化合物过去已经得到了充分研究，但直到最近才有可能研究它们在活细胞内的确切相互作用和作用方式。一方面，荧光染色和标记，另一方面，在显微镜下进行定性检测或在流式细胞仪和平板读数器中进行定量检测，使研究人员能够获得构建一个关于此类化合物在活细胞中如何起作用和相互作用的相当完整拼图所需的各种信息。这些基于细胞的生物分析技术辅以更传统的活性测定和蛋白质印迹法，并且越来越多地与蛋白质组学、化学遗传学筛选和mRNA分析等技术相结合，形成了一个用于“细胞内诊断”的强大平台。就氧化还原活性化合物而言，特别是活性硫物种（RSS），这些技术最近揭示了诸如“细胞硫醇稳态”等概念，但为了全面理解此类化合物为何以及如何（通常是选择性地）在不同生物体中起作用，还需要进行更多的研究。
