通过代谢组学和网络药理学剖析丹酚酸 B 防治糖尿病的潜在作用机制。

Dissection of the potential anti-diabetes mechanism of salvianolic acid B by metabolite profiling and network pharmacology.

机构信息

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin, China.

出版信息

Rapid Commun Mass Spectrom. 2022;36(1):e9205. doi: 10.1002/rcm.9205.

DOI:10.1002/rcm.9205

PMID:34636119

Abstract

RATIONALE

Salvianolic acid B (Sal B), the Q-marker in Salvia miltiorrhiza, was proved to present an obvious anti-diabetes effect when treated as a food intake. Until now, the metabolism feature, tissue distribution and anti-diabetes mechanism of Sal B have not been fully elucidated.

METHODS

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

RESULTS

A total of 31 metabolites were characterized in rats after ingestion of Sal B at a dosage of 40 mg/kg, including 1 in plasma, 19 in urine, 31 in feces, 0 in heart, 0 in liver, 0 in spleen, 1 in lung, 1 in kidney and 0 in brain. Among them, 18 metabolites were reported for the first time. Phase I reactions of hydrolysis, hydrogenation, dehydroxylation, hydroxylation, decarboxylation and isomerization, and phase II reactions of methylation were found in Sal B. Notably, decarboxylation and dehydroxylation were revealed in Sal B for the first time. The pharmacology network results showed that Sal B and its metabolites could regulate ALB, PLG, ACE, CASP3, MMP9, MMP2, MTOR, etc. The above targets were involved in insulin signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, etc. CONCLUSIONS: The metabolism feature of Sal B in vivo was systematically revealed, and its anti-diabetes mechanism for further pharmacological validations was predicted based on metabolite profiling and network pharmacology for the first time.

摘要

背景

丹参中的丹酚酸 B（Sal B）作为一种食品摄入已被证明具有明显的抗糖尿病作用。迄今为止，Sal B 的代谢特征、组织分布和抗糖尿病机制尚未完全阐明。

方法

采用超高效液相色谱-飞行时间质谱联用技术对大鼠灌胃 Sal B（剂量为 40mg/kg）后的代谢产物进行分析。通过网络药理学预测 Sal B 的潜在抗糖尿病机制。

结果

在大鼠体内摄入 Sal B 后，共鉴定出 31 种代谢产物，包括 1 种在血浆中，19 种在尿液中，31 种在粪便中，0 种在心脏中，0 种在肝脏中，0 种在脾脏中，1 种在肺中，1 种在肾脏中，0 种在大脑中。其中 18 种代谢产物为首次报道。Sal B 中存在水解、加氢、去羟化、羟化、脱羧和异构化等 I 相反应以及甲基化等 II 相反应。值得注意的是，Sal B 中首次发现了脱羧和去羟化反应。药理学网络结果表明，Sal B 及其代谢产物可以调节 ALB、PLG、ACE、CASP3、MMP9、MMP2、MTOR 等。上述靶点参与了胰岛素信号通路、PI3K-Akt 信号通路、HIF-1 信号通路、TNF 信号通路等。