Dai Yubei, Zhang Kailian, Wang Long, Xiong Ling, Huang Feihong, Huang Qianqian, Wu Jianming, Zeng Jing
School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
School of Basic Medical Science, Southwest Medical University, Luzhou 646000, China.
Metabolites. 2022 Nov 5;12(11):1074. doi: 10.3390/metabo12111074.
L. (), a well-known herbal medicine, has been proven to show effect against thrombocytopenia. However, metabolites of in vivo are still unclear, and the underlying mechanism of against thrombocytopenia from the aspect of metabolites have not been well elucidated. In this study, an improved analytical method combined with UHPLC-QTOF MS and a molecular network was developed for the rapid characterization of metabolites in vivo based on fragmentation patterns. Then, network pharmacology (NP) was used to elucidate the potential mechanism of against thrombocytopenia. As a result, a total of 1678 exogenous metabolites were detected in urine, feces, plasma, and bone marrow, in which 104 metabolites were tentatively characterized. These characterized metabolites that originated from plasma, urine, and feces were then imported to the NP analysis. The results showed that the metabolites from plasma, urine, and feces could be responsible for the pharmacological activity against thrombocytopenia by regulating the PI3K-Akt, MAPK, JAK-STAT, VEGF, chemokine, actin cytoskeleton, HIF-1, and pluripotency of stem cells. This study provides a rapid method for metabolite characterization and a new perspective of underlying mechanism study from the aspect of active metabolites in vivo.
L.（一种知名草药）已被证明对血小板减少症有疗效。然而，其体内代谢产物仍不清楚，且从代谢产物方面针对血小板减少症的潜在机制尚未得到充分阐明。在本研究中，开发了一种结合超高效液相色谱-四极杆飞行时间质谱（UHPLC-QTOF MS）和分子网络的改进分析方法，用于基于碎片模式快速表征体内代谢产物。然后，利用网络药理学（NP）阐明L.抗血小板减少症的潜在机制。结果，在尿液、粪便、血浆和骨髓中总共检测到1678种外源性代谢产物，其中104种代谢产物被初步表征。这些源自血浆、尿液和粪便的已表征代谢产物随后被导入NP分析。结果表明，血浆、尿液和粪便中的代谢产物可能通过调节PI3K-Akt、MAPK、JAK-STAT、VEGF、趋化因子、肌动蛋白细胞骨架、HIF-1和干细胞多能性来发挥抗血小板减少症的药理活性。本研究提供了一种代谢产物表征的快速方法，并从体内活性代谢产物方面为潜在机制研究提供了新的视角。
