Deciphering the metabolic profile and pharmacological mechanisms of Achyranthes bidentata blume saponins using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry coupled with network pharmacology-based investigation
Deciphering the metabolic profile and pharmacological mechanisms of Achyranthes bidentata blume saponins using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry coupled with network pharmacology-based investigation
复制标题
使用超高效液相色谱四极杆飞行时间质谱结合网络药理学研究破译牛膝皂苷的代谢特征和药理机制
DOI：
10.1016/j.jep.2021.114067
复制
发表时间：
2021-03-31
影响因子：
5.4
通讯作者：
Sun, Minghui
中科院分区：
文献类型：
--
作者：
Fu, Jun;Wu, Huan;Sun, Minghui
Ethnopharmacological relevance: Achyranthes bidentata Blume (AB) is a traditional Chinese medicine (TCM) widely used as a dietary supplement and anti-arthritis drug. Pharmacological studies have shown that Achyranthes bidentata Blume saponins (ABS) are the main bioactive ingredient. However, the metabolic profile and mechanisms of action of ABS against rheumatic arthritis (RA) remain to be established. Aim of the study: Our main objective was to investigate the metabolic profile and pharmacological activities of ABS against RA. Materials and methods: In this study, an analytical method based on ultra-performance liquid chromatographyquadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) coupled with a metabolism platform was developed for metabolic profiling of ABS in rat liver microsomes and plasma. Then, the in vivo metabolites of ABS and their targets associated with RA were used to construct the network pharmacological analysis. Gene ontology (GO) enrichment, KEGG signaling pathway analyses and pathway network analyses were performed. The therapeutic effect of ABS on RA was further evaluated using an adjuvant arthritis (AA) model and network pharmacology results validated via Western blot. Results: Overall, 26 and 21 metabolites of ABS were tentatively characterized in rat liver microsomes and plasma, respectively. The metabolic pathways of ABS mainly included M+O, M+O?H2, M+O2, and M+O2?H2. Data form network pharmacology analysis suggested that MAPK, apoptosis, PI3K-AKT and p53 signaling pathways contribute significantly to the therapeutic effects of ABS on RA. In pharmacodynamics experiments, ABS ameliorated the symptoms in AA rats in a dose-dependent manner and restored the homeostasis of pro/antiinflammatory factors. Western blot results further demonstrated a significant ABS-induced decrease in phosphorylation of ERK in the MAPK pathway (P < 0.01). Conclusion: Application of an analytical method based on UPLC-QTOF/MS, network pharmacology and validation experiments offers novel insights into the components and mechanisms of ABS that contribute to its therapeutic effects against RA, providing useful directions for further research.
