Evaluation of Biological Mechanisms of Eucommiae Folium in Hypertensive Kidney Injury by Integration of Untargeted Metabolomics and Network Pharmacology

Abstract

Hypertensive kidney injury (Hki) is one of the most common complications of hypertension. Early prevention and treatment of renal injury in patients with hypertension is great significance. The study, which used an integrated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS) analysis, network pharmacology approach, and plasma metabolomics, aimed to discover the active ingredients and therapeutic mechanisms of Eucommiae folium (Ef) in treating Hki. The chemical components of Ef were analyzed by UPLC-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS), and the "compound-target-disease" network was constructed by screening the closely related drug targets from the drug-target database, then the signaling pathways related to Hki were analyzed. Finally, the enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse-transcription polymerase chain reaction were used to test and verify the key targets in the common pathways of metabolomics and network pharmacology. The results indicated that Eucommiae folium might play an excellent role in treating Hki, likely through regulating the vascular endothelial growth factor signaling pathway, hypoxia inducible factor 1 (HIF-1) signaling pathway, and glycerophospholipid metabolism pathway, which were validated by increasing levels of nitric oxide, endothelial nitric oxide synthase and reducing levels of endothelin 1, angiotensin II, renin, cyclic guanosine monophosphate, blood urea nitrogen, and serum creatinine, as well as the reduced gene expression of Ache, Ddah2, Egfr, Lcat, Pla2g2a, Stat3 and Vegfa. The study systematically explored the protective mechanisms of Ef against Hki and also provided the practical treatment strategies of Hki from the Chinese herb.

UPLC‐MS analysis and network pharmacology‐based investigation into the active ingredients and molecular mechanisms of anti‐fatigue of male flowers with Eucommia ulmoides Oliv.

“…The maps of 24 MFEU active components were drawn by ChemBioDraw Ultra 12.0 software. In this paper, the targets of ingredients with MFEU were found on the SwissTargetPrediction website (http://www.swisstargetprediction.ch/) [13]. All targets were deleted duplicate and false positive by SwissTargetPrediction website; 24 active ingredients and 255 targets were obtained after integration; 988 targets of fatigue, anti‐fatigue were retrieved and integrated from GeneCard, OMIM database.…”

Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification

“…Mangiferin, isomangiferin and neomangiferin as anti-inflammatory components could inhibit AA metabolism. An integrated UPLC/MS metabolomics was used to discover bioactive ingredients of Eucommiae folium (Ef) in treating kidney injury [144]. The results indicated that Ef could regulate the vascular endothelial growth factor, hypoxia-inducible factor 1, and glycerophospholipid pathways.…”

Do wearing masks and preservatives have a combined effect on skin health?

“…Network toxicology can clarify the relationships between chemicals and the human body by considering the broader context of a biological network, which can elucidate the mechanism underlying adverse reactions of chemicals and highlight the complex regulation of signal pathways across multiple channels [ 20 ]. The metabolomics and network toxicology method could improve the accuracy and effectiveness [ 21 , 22 ].…”