Meotti Flavia Carla, Lemos de Andrade Edinéia, Calixto João B
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-000, São Paulo, SP, Brazil.
Handb Exp Pharmacol. 2014;223:1177-238. doi: 10.1007/978-3-319-05161-1_19.
The use of medicinal plants or other naturally derived products to relieve illness can be traced back over several millennia, and these natural products are still extensively used nowadays. Studies on natural products have, over the years, enormously contributed to the development of therapeutic drugs used in modern medicine. By means of the use of these substances as selective agonists, antagonists, enzyme inhibitors or activators, it has been possible to understand the complex function of many relevant targets. For instance, in an attempt to understand how pepper species evoke hot and painful actions, the pungent and active constituent capsaicin (from Capsicum sp.) was isolated in 1846 and the receptor for the biological actions of capsaicin was cloned in 1997, which is now known as TRPV1 (transient receptor potential vanilloid 1). Thus, TRPV1 agonists and antagonists have currently been tested in order to find new drug classes to treat different disorders. Indeed, the transient receptor potential (TRP) proteins are targets for several natural compounds, and antagonists of TRPs have been synthesised based on the knowledge of naturally derived products. In this context, this chapter focuses on naturally derived compounds (from plants and animals) that are reported to be able to modulate TRP channels. To clarify and make the understanding of the modulatory effects of natural compounds on TRPs easier, this chapter is divided into groups according to TRP subfamilies: TRPV (TRP vanilloid), TRPA (TRP ankyrin), TRPM (TRP melastatin), TRPC (TRP canonical) and TRPP (TRP polycystin). A general overview on the naturally derived compounds that modulate TRPs is depicted in Table 1.
使用药用植物或其他天然衍生产品来缓解疾病的做法可以追溯到几千年前，而且这些天然产品如今仍被广泛使用。多年来，对天然产品的研究极大地推动了现代医学中治疗药物的发展。通过将这些物质用作选择性激动剂、拮抗剂、酶抑制剂或激活剂，得以了解许多相关靶点的复杂功能。例如，为了弄清楚辣椒品种如何引发热感和痛感，1846年分离出了辛辣且具有活性的成分辣椒素（来自辣椒属），并于1997年克隆出了辣椒素生物作用的受体，如今该受体被称为TRPV1（瞬时受体电位香草酸亚型1）。因此，目前已对TRPV1激动剂和拮抗剂进行了测试，以寻找用于治疗不同疾病的新型药物类别。事实上，瞬时受体电位（TRP）蛋白是几种天然化合物的靶点，并且基于对天然衍生产品的了解合成了TRP的拮抗剂。在此背景下，本章重点关注据报道能够调节TRP通道的天然衍生化合物（来自植物和动物）。为了更清晰并便于理解天然化合物对TRP的调节作用，本章根据TRP亚家族分为几个组：TRPV（TRP香草酸亚型）、TRPA（TRP锚蛋白）、TRPM（TRP褪黑素）、TRPC（TRP典型）和TRPP（TRP多囊蛋白）。表1展示了调节TRP的天然衍生化合物的总体概述。
