Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial

PLoS One. 2015 May 15;10(5):e0126422. doi: 10.1371/journal.pone.0126422. eCollection 2015.

Abstract

The aim of this study was to evaluate the safety, tolerability and pharmacokinetics of single dose of Melissa officinalis extract which contained rosmarinic acid, including food-effects in healthy individuals. A total of eleven healthy individuals were randomly assigned to treatment arms in the two studies [Study 1 (fasted state) and Study 2 (fed state)]. Rosmarinic acid in serum was measured by a coulometric detection method using High-Performance Liquid Chromatography electrochemical detector. The serum concentration of total rosmarinic acid peaked at 1 hour after administration of Melissa officinalis extract containing 500mg rosmarinic acid in fasted state, with a maximum serum concentration 162.20 nmol/ L. The area under the curve for intact rosmarinic acid was calculated from the serum concentration-time profile to be 832.13 nmol • hour/ L. Food intake increases area under the curve and delayed time at which the maximum serum concentration. Rosmarinic acid supplementation did not affect liver, kidney, or blood cell function parameters. No adverse event was reported by any of the participants due to the study treatment. Single dose of Melissa officinalis extract containing 500 mg rosmarinic acid appears to be safe and tolerable in healthy individuals. Food intake increased the exposure of rosmarinic acid and delayed absorption of rosmarinic acid in healthy individuals.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromatography, High Pressure Liquid
  • Cinnamates / adverse effects
  • Cinnamates / blood
  • Cinnamates / pharmacokinetics
  • Depsides / adverse effects
  • Depsides / blood
  • Depsides / pharmacokinetics
  • Female
  • Humans
  • Kidney / drug effects
  • Liver / drug effects
  • Male
  • Melissa* / adverse effects
  • Plant Extracts / adverse effects
  • Plant Extracts / pharmacokinetics*
  • Plant Leaves
  • Rosmarinic Acid
  • Young Adult

Substances

  • Cinnamates
  • Depsides
  • Plant Extracts

Grants and funding

This work was supported in part by a Grant-in-Aid Scientific Research from the Science of the Ministry of Education, Culture, Sports, Science and Technology of Japan (MY, MN-S), a grant to the Amyloidosis Research Committee from the Ministry of Health, Labour, and Welfare, Japan (MY), and Research Project on Development of Agricultural Products and Foods with Health-promoting benefits (NARO) (SK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.