title: Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial.
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.
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Moeko
authors.initials: M
authors.lastname: Noguchi-Shinohara
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hamaguchi
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Iwasa
authors.affiliation: Department of Food and Life-Science, Takasaki University of Health and Welfare, Gunma, Japan.
authors.forename: Toshitada
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Environmental and Preventive Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D002934:Cinnamates / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D053630:Depsides / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D031334:Melissa / Q000009:adverse effects; D010936:Plant Extracts / Q000009:adverse effects / Q000493:pharmacokinetics*; D018515:Plant Leaves; D055815:Young Adult; D000097123:Rosmarinic Acid
chemical_list: D002934:Cinnamates; D053630:Depsides; D010936:Plant Extracts; D000097123:Rosmarinic Acid