Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, 19328, Amman, Jordan.
Chem Biol Interact. 2020 Oct 1;330:109178. doi: 10.1016/j.cbi.2020.109178. Epub 2020 Jul 29.
The capsaicin (vanilloid) receptor, TRPV1, is a heat-activated cation channel modulated by inflammatory mediators and contributes to acute and chronic pain. TRPV1 channel is one of the most researched and targeted mechanisms for the development of novel analgesics. Over the years, natural products have contributed enormously to the development of important therapeutic drugs used currently in modern medicine. A literature review was conducted using Medline, Google Scholar, and PubMed. Searching the literature resulted in listing 136 natural compounds that interacted with TRPV1 channel. These compounds were phytochemicals that belong to different chemical groups including vanilloids, flavonoids, alkaloids, terpenoids, terpenyl phenols, fatty acids, cannabinoids, sulfur_containing compounds, etc. Other natural TRPV1 modulators were of animal, fungal or bacterial origin. Some natural products were small agonists or antagonists of TRPV1. Others were protein venoms. Most in vitro studies utilized electrophysiological or calcium imaging techniques to study calcium flow through the channel using primary cultures of rat dorsal root and trigeminal ganglia. Other studies used hTRPV1 or rTRPV1 expressed in HEK239, CHO cells or Xenopus oocytes. In vivo studies concentrated on different pain models conducted mainly in mice and rats. In conclusion, natural products are highly diverse in their modulatory action on TRPV1. Many gaps in natural product research are present in distinguishing modality-specific from polymodal antagonists. Species' differences in TRPV1 functionality must be taken into account in any future study. Proceeding into clinical trials needs more efforts to discover potent TRPV1 antagonists devoid of hyperthermia, the main side effect.
辣椒素（香草醛）受体 TRPV1 是一种热激活阳离子通道，受炎症介质调节，与急性和慢性疼痛有关。TRPV1 通道是新型镇痛药开发中研究和靶向最多的机制之一。多年来，天然产物为开发目前现代医学中使用的重要治疗药物做出了巨大贡献。使用 Medline、Google Scholar 和 PubMed 进行了文献综述。文献搜索导致列出了 136 种与 TRPV1 通道相互作用的天然化合物。这些化合物是属于不同化学基团的植物化学物质，包括香草醛、类黄酮、生物碱、萜类、萜烯酚、脂肪酸、大麻素、含硫化合物等。其他天然 TRPV1 调节剂来自动物、真菌或细菌。一些天然产物是 TRPV1 的小分子激动剂或拮抗剂。其他是蛋白质毒液。大多数体外研究使用电生理学或钙成像技术，使用大鼠背根和三叉神经节的原代培养物研究钙通过通道的流动。其他研究使用在 HEK239、CHO 细胞或非洲爪蟾卵母细胞中表达的 hTRPV1 或 rTRPV1。体内研究主要集中在不同的疼痛模型上，这些模型主要在小鼠和大鼠中进行。总之，天然产物在调节 TRPV1 方面具有高度多样性。在区分特定模式和多模式拮抗剂方面，天然产物研究存在许多空白。在任何未来的研究中，都必须考虑 TRPV1 功能的物种差异。进入临床试验需要更多的努力来发现没有高热的有效 TRPV1 拮抗剂，高热是主要的副作用。
