Evaluation of Anti-Inflammatory Effects of Celery Leaf and Stem Extracts in LPS-Induced RAW 264.7 Cells Using Nitric Oxide Assay and LC-MS Based Metabolomics

Curr Issues Mol Biol. 2021 Nov 5;43(3):1876-1888. doi: 10.3390/cimb43030131.


The present work demonstrated and compared the anti-inflammatory effects of celery leaf (CLE) and stem (CSE) extracts. LC-MS-based metabolomics were an effective approach to achieve the biomarker identification and pathway elucidation associated with the reduction in inflammatory responses. The celery extracts suppressed LPS-induced NO production in RAW 264.7 cells, and CLE was five times more effective than CSE. Distinct differences were revealed between the control and celery-treated samples among the 24 characteristic metabolites that were identified. In celery-treated LPS cells, reversals of intracellular (citrulline, proline, creatine) and extracellular (citrulline, lysine) metabolites revealed that the therapeutic outcomes were closely linked to arginine metabolism. Reversals of metabolites when treated with CLE (aspartate, proline) indicated targeted effects on the TCA and urea cycles, while, in the case of CSE (histidine, glucose), the glycolysis and the pentose phosphate pathways were implicated. Subsequently, apigenin and bergapten in CLE were identified as potential biomarkers mediating the anti-inflammatory response.

Keywords: LC-MS; RAW 264.7 cells; celery; inflammation; metabolomics; plant.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology*
  • Apium / chemistry*
  • Chromatography, Liquid
  • Lipopolysaccharides / immunology
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Metabolome
  • Metabolomics / methods
  • Mice
  • Nitric Oxide / metabolism
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Plant Stems / chemistry
  • RAW 264.7 Cells
  • Tandem Mass Spectrometry


  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • Plant Extracts
  • Nitric Oxide