Systematic investigation of the pharmacological mechanism for renal protection by the leaves of Eucommia ulmoides Oliver using UPLC-Q-TOF/MS combined with network pharmacology analysis

Biomed Pharmacother. 2021 Aug:140:111735. doi: 10.1016/j.biopha.2021.111735. Epub 2021 May 19.

Abstract

Bark is the traditional medicinal component of Eucommia ulmoides Oliver (E. ulmoides). However, the demand for E. ulmoides medicinal materials seriously limits their sustainability. To alleviate resource constraints, the bioactivity of E. ulmoides leaves and its pharmacodynamic basis were investigated. In the present study, extracts of E. ulmoides leaves were found to display potential renal protective properties in rat glomerular mesangial (HBZY-1) cells treated with high levels of glucose, suggesting that they possess potential factors capable of treating diabetic nephropathy. Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to comprehensively characterize the chemical components of E. ulmoides leaves. A total of 83 possible chemical components, including 12 iridoids, 13 flavonoids, 14 lignans, 20 phenylpropanoids, 14 phenolic acids, and 10 additional components, were identified in E. ulmoides leaves. Network pharmacology was used for a preliminary exploration of the potential mechanism of action of renal protection afforded by E. ulmoides leaves towards diabetic nephropathy. The network pharmacology results were verified using a series of biological experiments. The present study provided the basis for the comprehensive development and utilization of E. ulmoides leaves and the discovery of potential drugs.

Keywords: E. ulmoides leaves; Network pharmacology; Pharmacological mechanism; Renal protective effects; UPLC-Q-TOF-MS.

MeSH terms

  • Aldehyde Reductase / metabolism
  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Chromatography, High Pressure Liquid
  • Diabetic Nephropathies / drug therapy*
  • Eucommiaceae*
  • Glucose / toxicity
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mesangial Cells / drug effects
  • Mesangial Cells / metabolism
  • Phytochemicals / analysis
  • Phytochemicals / pharmacology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Protective Agents / chemistry
  • Protective Agents / pharmacology*
  • Rats
  • Receptor, Insulin / metabolism
  • Tandem Mass Spectrometry

Substances

  • Insr protein, rat
  • Phytochemicals
  • Plant Extracts
  • Protective Agents
  • Akr1b1 protein, rat
  • Aldehyde Reductase
  • Receptor, Insulin
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat
  • Glucose