中药质量控制长期依赖少数化学成分定量，难以充分揭示成分含量与功效的内在关联。中药质量标志物（quality marker，Q-Marker）理论虽为“效-物结合”的质量评价提供了系统框架，但如何精准识别真正介导核心药效的关键成分仍是该领域的最大挑战。G蛋白偶联受体（G protein-coupled receptor，GPCR）是细胞感知微环境变化的关键门户，也是最具成药性的靶标家族之一，广泛参与神经、免疫、代谢及心血管等重要生理病理过程，已成为阐释中药多成分、多靶点调节机制的重要切入点。提出“以GPCR等靶标为核心的中药Q-Marker发现策略”，梳理了Q-Marker理论从化学指纹到生物活性指纹演进的趋势，系统综述了靶向GPCR的前沿技术（受体亲和色谱技术、高通量功能筛选平台、人工智能驱动的反向药物发现及多组学整合策略等），进而阐述了以GPCR为作用靶标的Q-Marker从候选成分确认到质量标准构建的完整流程。在机制解析层面，从GPCR-炎症轴、GPCR-代谢轴、GPCR-肠道菌群轴和GPCR-神经心血管轴4个维度阐释中药活性成分作为天然配体介导的药理网络。为建立“成分-靶点-功能”关联的Q-Marker评价体系提供从分子识别到功能验证的证据链，有助于弥补传统网络预测“重关联、轻验证”的不足。将GPCR受体药理学与中药质量控制相结合，可为确立兼具有效性与安全性指示意义的Q-Marker提供实验依据，对推动中药质量标准从化学含量测定走向整合评价、保障临床用药安全有效具有重要参考价值。

Traditional Chinese medicine (TCM) quality control has long relied on the quantitative determination of a limited number of chemical constituents, which fails to adequately reveal the intrinsic relationship between component content and pharmacological efficacy. Although the quality marker (Q-Marker) theory provides a systematic framework for efficacy-material-integrated quality evaluation of TCM, precisely identifying the key constituents that genuinely mediate core pharmacological effects remains a major challenge in the field. G protein-coupled receptors (GPCRs) are major cell-surface signaling receptors that sense extracellular signals and transduce them into intracellular responses. They also represent one of the most druggable classes of therapeutic targets. They play pivotal roles in a wide range of physiological and pathological processes, particularly those involving the nervous, immune, metabolic, and cardiovascular systems, and have become an important entry point for elucidating the multi-component, multi-target regulatory mechanisms of TCM. This paper explores a “GPCR and other target-centered discovery strategy for TCM Q-Markers”, reviews the evolutionary trajectory of Q-Marker theory from chemical fingerprinting to bioactivity fingerprinting, and systematically summarizes cutting-edge technologies for GPCR-based target identification, including receptor affinity chromatography, high-throughput functional screening platforms, artificial intelligence-driven reverse drug discovery, and multi-omics integration strategies. Furthermore, it elaborates the complete workflow of Q-Markers acting GPCR targets, from candidate component confirmation to quality standard establishment. At the mechanistic level, the pharmacological networks mediated by bioactive TCM constituents through their interactions with GPCRs are interpreted from four dimensions: the GPCR-inflammation, GPCR-metabolism, GPCR-gut microbiota, and GPCR-neurocardiovascular axes. This framework provides an evidence chain linking molecular recognition, target engagement, and functional validation to support the development of a Q-Marker evaluation system based on “component-target-function” relationships, thereby helping to overcome the limitation of conventional network pharmacology approaches, which often emphasize predicted associations over experimental target validation. Integrating GPCR receptor pharmacology with TCM quality control can provide an experimental basis for identifying Q-Markers that reflect both efficacy and safety. It also offers a useful reference for advancing TCM quality standards from chemical content determination toward integrated evaluation, thereby supporting the safety and efficacy evaluation of TCM in clinical use.

R285

湖南省创新型省份建设专项中国工程科技发展战略湖南研究院战略研究与咨询项目（2025WK1009）；中国工程院科技战略咨询项目“中药产业发展战略研究”（2025-32-15）