Metabolomics integrated with network pharmacology of blood-entry constituents reveals the bioactive component of Xuefu Zhuyu decoction and its angiogenic effects in treating traumatic brain injury

作者：Teng Li, Lianglin Zhang, Menghan Cheng, En Hu, Qiuju Yan, Yao Wu, Weikang Luo, Hong Su, Zhe Yu, Xin Guo, Quan Chen, Fei Zheng, Haigang Li, Wei Zhang, Tao Tang, Jiekun Luo, Yang Wang · 发表于：Chinese Medicine · 年份：2024 · DOI：10.1186/s13020-024-01001-0 · 被引用次数：52 · 研究领域：Traumatic Brain Injury and Neurovascular Disturbances、Metabolomics and Mass Spectrometry Studies、Traumatic Brain Injury Research

BACKGROUND: Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. OBJECTIVES: This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. METHODS: The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. RESULTS: Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, a...