京尼平苷酸的药理活性和药代动力学研究进展

李子威1,2, 戚胜兰2, 张庆光2, 陈陵3, 胡静3∗, 葛广波2∗, 黄丰1∗

(1. 云南中医药大学 中药学院, 云南 昆明 650500;2. 上海中医药大学 交叉科学研究院, 上海 201203;3. 上海中医药大学附属第七人民医院 肾病科, 上海 200137)

[摘要]　京尼平苷酸(geniposidic acid,GA)是一种天然环烯醚萜类化合物,广泛分布在茜草科、杜仲科、车前科等药用植物的根、茎、叶、花、树皮、果实和种子中。现代药理学研究表明,GA 具有脏器保护、抗炎、抗氧化、抗骨质疏松、抗神经退行性疾病、缓解心血管疾病等多种药理活性。GA 可通过上调抗炎、抗氧化关键因子提升细胞/ 机体的防御能力,同时能下调AhR、TLR4/MyD88 等促炎信号通路的关键节点蛋白进而发挥脏器保护等药理作用。药代动力学研究显示GA 口服后可在多个脏器分布(肾、肝、心、脾、肺等);且在疾病状态下该化合物的药代动力学行为会发生显著改变,主要表现为口服后的系统暴露显著增加。该文全面综述了GA 已报道的多种药理活性及其药理机制,同时系统总结了GA 的药代动力学行为和参数,以期为GA 相关中成药的临床精准应用和基于GA 的创新药物研发等提供理论依据和科学参考。

[关键词]　京尼平苷酸; 药理活性; 脏器保护; 抗炎抗氧化; 药代动力学

[Abstract]　Geniposidic acid (GA), a natural iridoid, exists in the roots, stems, leaves, flowers, bark, fruits, and seeds of medicinal plants of Rubiaceae, Eucommiaceae, and Plantaginaceae. Modern pharmacological studies have revealed that GA has multiple pharmacological activities, including organ-protective, anti-inflammatory, antioxidative, anti-osteoporosis, antineurodegenerative, and anti-cardiovascular effects. GA can enhance cell/ organism defenses by upregulating key anti-inflammatory and antioxidant cytokines, while downregulating key node proteins in pro-inflammatory signaling pathways such as AhR and TLR4/ MyD88, thereby exerting pharmacological effects such as organ protection. Pharmacokinetic investigations have suggested that after oral administration, GA can be distributed in multiple organs (kidney, liver, heart, spleen, lung, etc. ). In addition, the pharmacokinetic behavior of GA could be significantly altered under disease conditions, as demonstrated by a marked increase in systematic exposure. This article comprehensively summarizes the reported pharmacological activities and mechanisms and systematically analyzes the pharmacokinetic characteristics and key parameters of GA, with the aim of providing a theoretical basis and scientific reference for the precise clinical application of GA-related Chinese patent medicines, as well as for the investigation and development of innovative drugs based on GA.

[Key words]　geniposidic acid; pharmacological activity; organ protection; anti-inflammatory and antioxidative effects; pharmacokinetics