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

Moeko Noguchi-Shinohara, Kenjiro Ono, Tsuyoshi Hamaguchi, Kazuo Iwasa, Toshitada Nagai, Shoko Kobayashi, Hiroyuki Nakamura, Masahito Yamada, Moeko Noguchi-Shinohara, Kenjiro Ono, Tsuyoshi Hamaguchi, Kazuo Iwasa, Toshitada Nagai, Shoko Kobayashi, Hiroyuki Nakamura, Masahito Yamada

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Experimental time course for each…
Fig 1. Experimental time course for each participant.
Each participant completed three studies with a different RA dosage or placebo as designated by treatment group in the Latin square design. Blood samples were collected at baseline and 0.25, 0.5, 1, 2, 3, 6, 24, 48 hours after intake of RA or placebo on each intervention day. *1 indicates a 7-day controlled diet period. During this period, the participants were requested to consume foods that contain minimal amounts of polyphenols, such as rice and fish. * 2 indicates a 10-day wash-out period.
Fig 2. Serum concentration-time profiles in the…
Fig 2. Serum concentration-time profiles in the serum concentration of rosmarinic acid (RA) before and 0.25, 0.5, 1, 2, 3, 6, 24 and 48 hours after intake of Melissa officinalis extract.
Data show of intact and conjugated forms of RA after administration of 500mg RA [fasted (2A)/ fed state (2B)] and 250mg RA (fasted state) (2C). Each point is expressed as the mean ± SEM, n = 6.

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