Plant extracts have played a significant role in traditional medicine for centuries, contributing to improved health and the treatment of various human illnesses. G protein-coupled receptors (GPCRs) are crucial in numerous physiological functions, and there is growing evidence suggesting their involvement in the therapeutic effects of many plant extracts. In recent years, scientists have identified an expanding number of isolated molecules responsible for the biological activity of these extracts, with many believed to act on GPCRs. This article critically reviews the evidence supporting the modulation of GPCR function by these plant-derived molecules through direct binding. Structural information is now available for some of these molecules, allowing for a comparison of their binding mode with that of endogenous GPCR ligands. The final section explores future trends and challenges, focusing on the identification of new plant-derived molecules with both orthosteric and allosteric binding modes, as well as innovative strategies for designing GPCR ligands inspired by these plant-derived compounds. In conclusion, plant-derived molecules are anticipated to play an increasingly vital role as therapeutic drugs and serve as templates for drug design.

Significance Statement This minireview summarizes the most pertinent publications on isolated plant-derived molecules interacting with GPCRs and comments on available structural information on GPCR- plant-derived ligand pairs. Future challenges and trends for the isolation and characterization of plant-derived molecules and drug design are discussed.

几个世纪以来，植物提取物在传统医学中发挥着重要作用，有助于改善健康和治疗各种人类疾病。G 蛋白偶联受体 (GPCR) 在许多生理功能中至关重要，并且越来越多的证据表明它们参与许多植物提取物的治疗效果。近年来，科学家们发现了越来越多的分离分子，这些分子与这些提取物的生物活性有关，其中许多分子被认为作用于 GPCR。本文批判性地回顾了支持这些植物源性分子通过直接结合调节 GPCR 功能的证据。现在可以获取其中一些分子的结构信息，从而可以将它们的结合模式与内源 GPCR 配体的结合模式进行比较。最后一部分探讨了未来的趋势和挑战，重点是鉴定具有正构和变构结合模式的新植物衍生分子，以及受这些植物衍生化合物启发设计 GPCR 配体的创新策略。总之，植物源分子预计将作为治疗药物发挥越来越重要的作用，并作为药物设计的模板。

重要性声明这篇小型评论总结了有关分离的植物源分子与 GPCR 相互作用的最相关出版物，以及对 GPCR 植物源配体对的可用结构信息的评论。讨论了植物源分子的分离和表征以及药物设计的未来挑战和趋势。