通过代谢组学和网络药理学解析补骨脂素 - 补骨脂果实中的质量控制标志物 - 潜在的抗骨质疏松机制。

Dissection of potential anti-osteoporosis mechanism of isopsoralen - a quality control marker in Psoraleae Fructus - by metabolite profiling and network pharmacology.

机构信息

Beihai Hospital of Chinese Medicine, Beihai, Guangxi, China.

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, China.

出版信息

Rapid Commun Mass Spectrom. 2024 Oct 15;38(19):e9880. doi: 10.1002/rcm.9880.

DOI:10.1002/rcm.9880

PMID:39159996

Abstract

RATIONALE

Isopsoralen (ISO), a quality control marker (Q-marker) in Psoraleae Fructus, is proven to present an obvious anti-osteoporosis effect. Until now, the metabolism and anti-osteoporosis mechanisms of ISO have not been fully elucidated, greatly restricting its drug development.

METHODS

The metabolites of ISO in rats were profiled by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-osteoporosis mechanism of ISO in vivo was predicted by using network pharmacology.

RESULTS

A total of 15 metabolites were characterized in rats after ingestion of ISO (20 mg/kg/day, by gavage), including 2 in plasma, 12 in urine, 6 in feces, 1 in heart, 3 in liver, 1 in spleen, 1 in lung, 3 in kidney, and 2 in brain. The pharmacology network results showed that ISO and its metabolites could regulate AKT1, SRC, NFKB1, EGFR, MAPK3, etc., involved in the prolactin signaling pathway, ErbB signaling pathway, thyroid hormone pathway, and PI3K-Akt signaling pathway.

CONCLUSIONS

This is the first time for revealing the in vivo metabolism features and potential anti-osteoporosis mechanism of ISO by metabolite profiling and network pharmacology, providing data for further verification of pharmacological mechanism.

摘要

原理

补骨脂素（ISO）是补骨脂属果实中的一种质量控制标志物（Q 标志物），已被证明具有明显的抗骨质疏松作用。到目前为止，ISO 的代谢和抗骨质疏松机制尚未完全阐明，这极大地限制了其药物开发。

方法

采用超高效液相色谱-飞行时间质谱联用技术对 ISO 在大鼠体内的代谢产物进行了分析。通过网络药理学预测了 ISO 在体内的潜在抗骨质疏松机制。

结果

灌胃给予 ISO（20mg/kg/天）后，在大鼠体内共鉴定出 15 种代谢产物，包括 2 种在血浆中，12 种在尿液中，6 种在粪便中，1 种在心，3 种在肝，1 种在脾，1 种在肺，3 种在肾，2 种在脑。药理学网络结果表明，ISO 及其代谢产物可调节 AKT1、SRC、NFKB1、EGFR、MAPK3 等参与催乳素信号通路、ErbB 信号通路、甲状腺激素通路和 PI3K-Akt 信号通路的物质。