Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans.
BACKGROUND
Rosmarinic acid (RA) is a natural polyphenolic substance contained in many Lamiaceae herbs such as Perilla frutescens. Previous studies have shown RA has antioxidative and anti-inflammatory activity. However, little is known on the absorption, metabolism, degradation and excretion of RA.


OBJECTIVE
The aim of this study in healthy humans was to determine the absorption, metabolism, and urinary excretion of RA after a single intake of perilla extract (PE).


METHODS
Six healthy men (mean age 37.2 +/- 6.2 y and mean body mass index 22.0 +/- 1.9 kg/m(2)) were enrolled in the study that was a crossover design involving single intakes of PE containing 200 mg RA and placebo with a 10 day interval between treatments. Blood samples were collected before intake and at designated time intervals, while urine samples were collected over the periods 0-6 h, 6-24 h and 24-48 h after intake. RA and its related metabolites in plasma and urine were measured by LC-MS.


RESULTS
RA, methylated RA (methyl-RA), caffeic acid (CAA), ferulic acid (FA) and a trace of m-coumaric acid (COA) were detected in the urine after intake of PE. In plasma, RA, methyl-RA and FA were detected, with maximum levels obtained 0.5, 2 and 0.5 h after intake of PE, respectively. The majority of these components in both plasma and urine were present as conjugated forms (glucuronide and/or sulfated). The proportion of RA and its related metabolites excreted in the urine was 6.3 +/- 2.2% of the total dose, with approximately 75% of these components being excreted within 6 h after intake of PE.


CONCLUSIONS
RA contained in PE was absorbed, conjugated and methylated following intake, with a small proportion of RA being degraded into various components, such as conjugated forms of CAA, FA and COA. These metabolites were then rapidly excreted in the urine.
Nutritional Science Center, Health and Bioscience Laboratories, Meiji Seika Kaisha, Ltd., Sakado-shi, Saitama 350-0289, Japan. seigo_baba@meiji.co.jp
Seigo
S
Baba
Naomi
N
Osakabe
Midori
M
Natsume
Akiko
A
Yasuda
Yuko
Y
Muto
Kyoko
K
Hiyoshi
Hirohisa
H
Takano
Toshikazu
T
Yoshikawa
Junji
J
Terao
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002109:Caffeic Acids / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000187:drug effects / Q000378:metabolism; D002934:Cinnamates / Q000378:metabolism* / Q000652:urine; D003373:Coumaric Acids / Q000378:metabolism; D018592:Cross-Over Studies; D053630:Depsides; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008745:Methylation / Q000187:drug effects; D008875:Middle Aged; D031344:Perilla frutescens / Q000378:metabolism; D010936:Plant Extracts; D018514:Plant Structures; D012016:Reference Values; D015842:Serine Proteinase Inhibitors / Q000378:metabolism* / Q000652:urine; D000097123:Rosmarinic Acid
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015415:Biomarkers; D002109:Caffeic Acids; D002394:Catechol O-Methyltransferase; D002934:Cinnamates; D003373:Coumaric Acids; D053630:Depsides; D010936:Plant Extracts; D015842:Serine Proteinase Inhibitors; D000097123:Rosmarinic Acid; C004999:ferulic acid; C040048:caffeic acid