Optimization of an Extraction Solvent for Angiotensin-Converting Enzyme Inhibitors from Hibiscus sabdariffa L. Based on Its UPLC-MS/MS Metabolic Profiling

Molecules. 2020 May 14;25(10):2307. doi: 10.3390/molecules25102307.

Abstract

Hibiscus species (Malvaceae) have been long used as an antihypertensive folk remedy. The aim of our study was to specify the optimum solvent for extraction of the angiotensin-converting enzyme inhibiting (ACEI) constituents from Hibiscus sabdariffa L. The 80% methanol extract (H2) showed the highest ACEI activity, which exceeds that of the standard captopril (IC50 0.01255 ± 0.00343 and 0.210 ± 0.005 µg/mL, respectively). Additionally, in a comprehensive metabolomics approach, an ultra-performance liquid chromatography (UPLC) coupled to the high resolution tandem mass spectrometry (HRMS) method was used to trace the metabolites from each extraction method. Interestingly, our comprehensive analysis showed that the 80% methanol extract was predominated with secondary metabolites from all classes including flavonoids, anthocyanins, phenolic and organic acids. Among the detected metabolites, phenolic acids such as ferulic and chlorogenic acids, organic acids such as citrate derivatives and flavonoids such as kaempferol have been positively correlated to the antihypertensive potential. These results indicates that these compounds may significantly contribute synergistically to the ACE inhibitory activity of the 80% methanol extract.

Keywords: ACE inhibition; Hibiscus; LC/MS; chemometry; extraction; metabolomics.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / chemistry*
  • Angiotensin-Converting Enzyme Inhibitors / isolation & purification
  • Antihypertensive Agents / chemistry*
  • Antihypertensive Agents / isolation & purification
  • Chlorogenic Acid / chemistry
  • Chlorogenic Acid / isolation & purification
  • Chromatography, High Pressure Liquid
  • Citric Acid / chemistry
  • Citric Acid / isolation & purification
  • Coumaric Acids / chemistry
  • Coumaric Acids / isolation & purification
  • Enzyme Assays
  • Hibiscus / chemistry*
  • Humans
  • Kaempferols / chemistry
  • Kaempferols / isolation & purification
  • Liquid-Liquid Extraction / methods*
  • Metabolome
  • Methanol / chemistry*
  • Peptidyl-Dipeptidase A / chemistry*
  • Peptidyl-Dipeptidase A / metabolism
  • Plant Extracts / chemistry
  • Quinic Acid / analogs & derivatives
  • Quinic Acid / chemistry
  • Quinic Acid / isolation & purification
  • Secondary Metabolism / physiology
  • Solutions
  • Solvents / chemistry*
  • Structure-Activity Relationship
  • Tandem Mass Spectrometry

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Coumaric Acids
  • Kaempferols
  • Plant Extracts
  • Solutions
  • Solvents
  • caffeoylquinic acid
  • Quinic Acid
  • Citric Acid
  • Chlorogenic Acid
  • kaempferol
  • ferulic acid
  • ACE protein, human
  • Peptidyl-Dipeptidase A
  • Methanol