Dynamics of the Cellular Metabolism of Leptosperin Found in Manuka Honey

J Agric Food Chem. 2019 Oct 2;67(39):10853-10862. doi: 10.1021/acs.jafc.9b03894. Epub 2019 Sep 20.


Leptosperin (methyl syringate β-d-gentiobioside) is abundantly found in manuka honey, which is widely used because of its antibacterial and possible anti-inflammatory activities. The aim of this study was to examine the molecular mechanism underlying the metabolism of leptosperin. Five phytochemicals (leptosperin, methyl syringate (MSYR), glucuronate conjugate of MSYR (MSYR-GA), sulfonate conjugate of MSYR (MSYR-S), and syringic acid (SYR)) were separately incubated with HepG2 and Caco-2 cells. After incubation, we found that the concentration of MSYR decreased, whereas the concentrations of SYR, MSYR-GA, and MSYR-S increased. By profiling with inhibitors and carboxylesterases (CES1, 2), we found that the conversion from MSYR to SYR was mediated by CES1. Lipopolysaccharide-stimulated RAW264.7 cells restored MSYR-GA to MSYR possibly by the secreted β-glucuronidase. All of the mice administered with leptosperin, MSYR, or manuka honey showed higher MSYR (13.84 ± 11.51, 14.29 ± 9.19, or 6.66 ± 2.30 nM) and SYR (1.85 ± 0.66, 6.01 ± 1.20, or 8.16 ± 3.10 nM) levels in the plasma compared with that of the vehicle controls (3.33 ± 1.45 (MSYR) and 1.85 ± 0.66 (SYR) nM). The findings of our study indicate that the unique metabolic pathways of these compounds may account for possible functionalities of manuka honey.

Keywords: carboxylesterase; leptosperin; metabolism; methyl syringate; syringic acid.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Female
  • Flowers / chemistry
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / analysis
  • Gallic Acid / metabolism
  • Glycosides / analysis
  • Glycosides / metabolism*
  • Hep G2 Cells
  • Honey / analysis*
  • Humans
  • Leptospermum / chemistry
  • Mice
  • Mice, Inbred ICR


  • Glycosides
  • leptosperin
  • methyl syringate
  • Gallic Acid
  • syringic acid