Human pharmacokinetics of rosmarinic acid

Rosmarinic acid (RA) represents ester of caffeic acid and 3,4-dihydroxyphenyllactic acid. It was originally isolated from Rosmarinus officinalis, and it is commonly detected in plants from subfamily Nepetoideae, family Lamiaceae, as well as in other plant families 1. Biological activities recorded for RA include antioxidant, antibacterial, anti-inflamatory, antidepressant and many other effects 2; this compound is believed to be responsible for prominent antiviral effects of some Lamiceae plants (e.g. lemon balm use in herpes labialis), including antiretroviral activity 3. Pharmacokinetics of RA was first studied in animal models, mainly in rats2. Main data were discovered this way, after which human studies showed similarities and differences in absorption, distribution, metabolism and elimination. Phenolic compounds with complex structure, including RA, generally have limited absorption in digestive tract2. Current knowledge suggests that intestinal microbials are
significant in processes of RA metabolism coupled with absorption. Catabolic activity is mediated by enzymes specific for gut bacteria results in less complex compounds, further more easily available in human organism 2,4,5. Simultaneous intake of food slightly reduces Cmax and delays Tmax of RA, with high interindividual differences 4. Concerning topical application of RA, penetration through human skin in relatively poor, suggesting only local effects of applied RA pharmaceutical formulations 6. Data suggest that distribution of RA in mediated by human serum albumin, and that hydrophobic interactions are responsible for bonding 7.
RA undergoes several steps of metabolism. Initial step in metabolism includes process of conjugation, as it can be seen by reached peaks of free and conjugated forms of RA.This metabolism is fast, as these levels are achieved in 0.5 hour. Another process of metabolism is methylation, and methyl-RA reached peak after 2 hours5. With increase of ingested amount of RA, concentrations of free forms are elevated, suggesting saturation kinetics of conjugating process 4. Degradational product ferulic acid was also detected after 0.5 h 5. Studies mainly investigated urinary elimination of RA. The compound was mainly excreted as free and conjugated forms RA and methyl-RA, although some conjugates of degradational products such as caffeic acid, m-coumaric acid and ferulic acid were also detected. Again, as well as metabolism, process of renal elimination was fast, approximately within 6 h 5. In conclusion, human pharmacokinetics of RA remains to be fully investigated. Further researches will give more data on this compound’s kinetics and explain its beneficial
effects for human health.