葛根芩连汤出自东汉张仲景《伤寒论》，由葛根、黄芩、黄连、甘草4味中药组成，具有解肌清热、止泻止痢之功，是治疗表邪内陷、里热炽盛所致热利证的经典名方。近年来，复方化学表征、体内暴露、肠道菌群-代谢物轴、糖脂代谢、动脉粥样硬化及炎症性肠病等研究不断深入，另有研究提示共煎体系中的天然纳米颗粒和成分间自组装结构可能影响活性成分的释放、结肠吸收、组织分布及药效。在保持“化学成分-药理作用-临床应用-质量标志物预测”主线的基础上，系统整合近年复方指纹与多成分定量、药动学、天然纳米颗粒、巨噬细胞极化、焦亡/铁死亡、肠道微生态及循证临床研究，并依据质量传递与溯源、成分特有性、成分有效性、复方配伍环境和成分可测性“五原则”，提出葛根素、3′-羟基葛根素、3′-甲氧基葛根素、大豆苷、大豆苷元、黄芩苷、黄芩素、汉黄芩苷、汉黄芩素、千层纸素A、小檗碱、黄连碱、表小檗碱、巴马汀、药根碱、甘草苷、异甘草苷、甘草素、甘草酸及甘草次酸20个潜在质量标志物，并构建核心指标与扩展指标相结合的分层评价思路，以期为葛根芩连汤全过程质量控制和临床精准应用提供依据。

Gegen Qinlian Decoction (葛根芩连汤, GQD), originated from Treatise on Febrile Diseases, consists of Gegen (Puerariae Lobatae Radix), Huangqi (Scutellariae Radix), Huanglian (Coptidis Rhizoma) and Gancao (Glycyrrhizae Radix et Rhizoma), has the functions of relieving muscle, clearing heat, stopping diarrhea and dysentery, which is a classic prescription for treating heat-induced syndrome caused by internal invasion of exterior pathogenic factors and intense internal heat. In recent years, research on compound chemical characterization, in vivo exposure, the gut microbiota-metabolite axis, glycolipid metabolism, atherosclerosis and inflammatory bowel disease has been continuously deepened. Recent evidence also suggests that natural nanoparticles and self-assembled structures formed during co-decoction may influence the release, colonic absorption, tissue distribution, and pharmacological effects of active constituents. On the basis of maintaining the main line of “chemical constituents-pharmacological actions-clinical applications-quality marker (Q-Marker) prediction”, this review integrates recent evidence from compound fingerprint and multi-component quantification, pharmacokinetics, natural nanoparticles, macrophage polarization, pyroptosis/ferroptosis, intestinal microecology, and evidence-based clinical studies. Based on the “five principles” of quality transfer and traceability, ingredient specificity, ingredient effectiveness, compound compatibility environment and ingredient testability, 20 candidate Q-Markers are proposed, including puerarin, 3′-hydroxypuerarin, 3′-methoxypuerarin, daidzin, daidzein, baicalin, baicalein, wogonoside, wogonin, oroxylin A, berberine, coptisine, epiberberine, palmatine, jatrorrhizine, liquiritin, isoliquiritin, liquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid. A hierarchical evaluation strategy combining core and extended indicators is proposed to provide a basis for the full-process quality control and precise clinical application of GQD.

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国家自然科学基金青年项目（82505220）；辽宁省科技计划联合计划自然科学基金面上项目（2025-MSLH-483）；辽宁省教育厅自主选题项目（LJ212410162016）