Guan Huanyu, Li Pengfei, Wang Qian, Zeng Fanli, Wu Jiashuo, Zhang Fangqing, Liao Shanggao, Shi Yue
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, P. R. China.
State Key Laboratory of Functions and Applications of Medicinal Plants & School of Pharmacy, Guizhou Medical University, Guizhou, 550025, P. R. China.
J Sep Sci. 2022 Sep;45(18):3459-3479. doi: 10.1002/jssc.202200370. Epub 2022 Jul 28.
Shengjiang Xiexin decoction, a traditional Chinese medical formula, has been utilized to alleviate the delayed-onset diarrhea induced by irino tecan. However, the chemical constituents of this formula and the activities of its constituents remain unclear. In this study, ultrahigh-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry was employed to comprehensively analyze the chemical constituents of Shengjiang Xiexin decoction. A total of 270 components, including flavonoids, coumarins, triterpenoids, alkaloids, diarylheptanoids and others, were identified or characterized. Multidrug resistance-associated protein 2 is an efflux transporter responsible for regulating drug absorption. A total of 20 characteristic components from the formula were selected to evaluate their effects on the function of multidrug resistance-associated protein 2 using the vesicular transport assay. Glycyrrhizic acid and glycyrrhetinic acid were identified as potential multidrug resistance-associated protein 2 inhibitors, while 9 flavonoid aglycones increased the uptake of the substrate [ H]-estradiol 17-β-glucuronide in the vesicles. This was the first systematic investigation of the chemical constituents from Shengjiang Xiexin decoction and the effect of its characteristic components on the transporter. The results offered a basis for further exploring the detoxification mechanisms of this formula and its interactions with other drugs.
生姜泻心汤是一种中药方剂,已被用于缓解伊立替康引起的迟发性腹泻。然而,该方剂的化学成分及其成分的活性仍不清楚。在本研究中,采用超高效液相色谱-四极杆/轨道阱高分辨质谱法对生姜泻心汤的化学成分进行了全面分析。共鉴定或表征了270种成分,包括黄酮类、香豆素类、三萜类、生物碱类、二芳基庚烷类等。多药耐药相关蛋白2是一种负责调节药物吸收的外排转运蛋白。从该方剂中选取了20种特征成分,采用囊泡转运试验评估它们对多药耐药相关蛋白2功能的影响。甘草酸和甘草次酸被鉴定为潜在的多药耐药相关蛋白2抑制剂,而9种黄酮苷元增加了囊泡中底物[H]-雌二醇17-β-葡萄糖醛酸苷的摄取。这是首次对生姜泻心汤的化学成分及其特征成分对转运蛋白的影响进行系统研究。研究结果为进一步探索该方剂的解毒机制及其与其他药物的相互作用提供了依据。