Mass spectrometry-based urinary metabolomics for the investigation on the mechanism of action of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves against ischemic stroke in rats. (15th September 2019)

• Record Type: Journal Article
• Authors: Wang, Rongjin; Shi, Liqiang; Liu, Shu; Liu, Zhiqiang; Song, Fengrui; Sun, Zhiheng; Liu, Zhongying
• Is Part Of: Journal of ethnopharmacology. Volume 241(2019)
• Publication Date: 2019-09-15
• Subjects: Metabolomics -- Ischemic stroke -- Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves -- UPLC-Q-TOF/MS; 2-VO two-vessel occlusion -- COX-2 cyclooxygenase-2 -- E. senticosus Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. -- ESL Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves -- ELISA enzyme-linked immunosorbent assay -- H&E haematoxylin and eosin -- HPLC High-performance liquid chromatography -- LC-MS liquid chromatography-mass spectrometry -- MAO monoamine oxidase -- MS mass spectrometry -- NOS nitric oxide synthase -- OPLS-DA orthogonal projection to latent structures squares-discriminant analysis -- PCA principal component analysis -- PLS-DA partial least squares discriminant analysis -- PG prostaglandins -- QC quality control -- TCM Traditional Chinese medicines -- UPLC-Q-TOF/MS ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry -- VIP variable importance on projection; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2019.111969
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: As a traditional Chinese medicine, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) can treat ischemic, neurasthenia, and hypertension diseases. However, only few studies have been conducted on the mechanism of action of ESL for ischemic disease treatment. Aim of the study: This study aimed to discover the potential biomarkers in the rats caused by ischemic stroke and build a gene–enzyme–biomarker network to explore the mechanism of ESL treatment on ischemic stroke further. Materials and methods: The urinary metabolomics strategy was developed by combining UPLC-Q-TOF/MS with multivariate data analysis. The gene-enzyme-biomarker network was built by Cytoscape 3.6.0 on the basis of the potential biomarkers filtered out via urinary metabolomic analysis. Then, the potential target enzymes of ESL in the treatment of ischemic stroke were selected for further validation analysis via the ELISA kits. Results: A total of 42 biomarkers associated with ischemic stroke have been identified, among which 38 species can be adjusted by ESL, including 5′-methylthioadenosine, prostaglandin A2, l-methionine, aldosterone, 11b-hydroxyprogesterone, prostaglandin E3, dehydroepiandrosterone, taurine, 5-methoxyindoleacetate, and p-cresol glucuronide. These biomarkers were involved in several metabolic pathways, including taurine and hypotaurine, arachidonic acid, cysteine and methionine, steroid hormone biosynthesis, tryptophan, and tyrosine metabolism pathways. The gene–enzyme–biomarker network was built, and three predicted target proteins, including cyclooxygenase-2 (COX-2), monoamine oxidase (MAO), and nitric oxide synthase (NOS), were selected as the potential target enzymes for ESL in ischemic stroke treatment. Conclusions: All results showed that ESL can play a therapeutic role in treating ischemic stroke through different pathways. This study will provide an overall view of the mechanism underlying the action of ESL against ischemic stroke. Graphical abstract: Image 1