Rosmarinic Acid

Last Updated: September 28 2022

Rosmarinic Acid is a polyphenol similar to caffeic acid (found in coffee) and is in high levels in Perilla Oil and Rosemary, from which it draws its name. It is a general anti-oxidant and health compound, and seen as 'healthy'.

Rosmarinic Acid is most often used for.

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    Sources and structure



    Rosmarinic acid is found the following food products and spices:

    • Perilla frutescens,[1] the seeds from which Perilla Oil is derived from at 1.716.9μg/g in the seeds (49% of total phenolics[2]) with a glucoside of rosmarinic acid (rosmarinic acid-3-O-glucoside) at 1752.7μg/g (48% total phenolics[2]); reaching 0.34% perilla seed oil by weight[2]
    • Rosemary[3] from where it derives its name
    • The spice herbs Sage,[4] Savory,[5] Mint,[6] and Thyme[7]
    • Basil[8] and the Ayurvetic medicine Holy Basil[9]

    The following dietary supplements:

    And a variety of uncommon plants including:

    • Clerodendranthus spicatus (Thunberg)[11]
    • Verbascum xanthophoeniceum (Scrophulariaceae)[12]
    • Heliotropium foertherianum (Boraginaceae)[13]

    Rosmarinic acid is a fairly widespread component of plants that is not limited to one particular plant family, but is found in higher than normal levels in some dietary supplements where it mediates many benefits associated with the supplement



    It is structurally a dimer of caffeic acid and 3,4-dihydroxyphenyllactic acid, bound by an ester linkage[14] and known as a phenylpropanoid.[12]






    Ingested rosmarinic acid is found systemically in its intact form, and also as various metabolites such as m-coumaric acid, m-phenylhydroxypropionic acid, and sulfated forms of caffeic, coumaric and ferulic acids.[15][16] These same metabolites are found in human blood/urine after ingestion.[17][18]

    Rosmarinic acid is methylated into methyl-rosmarininc acid via the catechol-o-methyltransferase (COMT) enzyme.[18]

    Ingestion of Perilla Extract (a common source of rosmarinic acid) containing 200mg Rosmarininc Acid while fasted results in approximately a peak concentration of 1.15+/-0.28umol/L in the plasma after 30 minutes, and the methylated metabolite (methyl-rosmarinic acid) may rise to a peak of 0.65+/-0.07umol/L at the 2 hour mark.[18] Up to 75% of Rosmarinic acid and its metabolites are excreted in the first 6 hours after ingestion. There are differences between rats and humans in this regard, with rats excreting more as a glucuronide conjugate and humans as a sulfate conjugation.[18]

    In rats, it has been reported that Rosmarinic acid can be absorbed through the skin, and the build-up of rosmarinic acid favors skin, muscle, and bone deposition rather than organ deposition percutaneously.[19] The absolute bioavailability in this study was 60%, enhanced by ethanol solvent, and a dose of 3mg over 20cm2 was used.


    Enzymatic Interactions

    Rosmarinic Acid appears to inhibit human organic anion transporter 1 (SLC22A6) and 3 (SLC22A8) with inhibitory constants (Ki values) of 0.35+/-0.06uM and 0.55+/-0.25uM respectively via competitive inhibition.[20]


    Cardiovascular Health



    Rosmarinic acid contributes to endothelial (blood vessel) and blood cell health. The former is typically indirect via systemic anti-oxidation and anti-inflammation (as discussed previously). In regards to the latter, rosmarinic acid can ease hemolysis, the breaking of red blood cells, via C3-convertase inhibition.[21]


    Inflammation and Immunology



    Rosmarinic Acid seems to be able to suppress 5-lipoxygenase and 5-HETE synthesis (a pro-inflammatory compound in the omega-6 metabolic chain). Unlike caffeic acid (a related compound), rosmarinic acid does not affect prostaglandin synthesis per se.[25]


    Interventions on Inflammation

    When tested in rats via an edema test, Rosmarinic acid is able to suppress the inflammatory response from administered TPA (pro-inflammatory agent), and a reduction in the oxidative increases by TPA were also observed.[26]


    Interventions on Allergies

    Oral supplementation of Perilla oil (in mice) has been demonstrated to suppress the allergic response by 43% at an oral dose of 500mg/kg, as assessed by an ear-passive cutaneous anaphylaxis test.[27] Later, a human study consisting of 30 persons aged 21-53 with mild cedar allergies (who get stuffy noses during allergy season) were given either 50mg Rosmarinic acid, 200mg, or placebo to be taken with breakfast for 21 days.[28] Rosmarinic acid appeared to be effective in suppressing allergies in a dose-dependent manner, with 30% of the placebo group reporting symptom relief compared to 55.6% of the 50mg group and 70% of the 200mg group.[28]

    In the human study, there was a significant reduction in immune cells in the nasal mucus by the third day with 200mg (PMNLs down to 84% of baseline, Eosinophils down to 86% of baseline, Neutrophils down to 72% of baseline) but it appeared to normalize, with no significant difference at day 21.[28]

    Preliminary evidence suggests that a once-daily dose of Rosmarinic acid may help allergy sufferers


    Interactions with Oxidation

    Rosmarinic Acid has been shown to exert anti-oxidant effects in vitro against superoxide radicals and hydroxyl radicals.[29]

    It can also prevent the oxidation of LDL molecules, and works synergistically in this regard with lycopene.[30]


    Interactions with Organ Systems



    10, 25, or 50mg/kg Rosmarinic acid was given orally once daily for two days, each time 6 hours after injection of the hepatoxin CCl4. Rosmarinic acid itself did not alter liver weight (absolute or relative to the body) nor ALT levels, but 50mg/kg after CCl4 normalized 56% of the increase in absolute liver weight (only 26% relative weight changes) while reducing the spike in ALT by 23%.[31] There was a reported reduction in liver necrosis and fibrosis associated with Rosmarinic acid.[31]


    Interactions with Cancer Metabolism



    Rosmarininc acid (typically via Perilla Oil) is used topically to combat skin carcinogenesis. This has been shown in rat models[32][33] alongside general topical anti-inflammatory benefits, and appears to also be absorbed via the skin in humans in the form of 'perillyl alcohol'.[34][35]

    3.^al-Sereiti MR, Abu-Amer KM, Sen PPharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentialsIndian J Exp Biol.(1999 Feb)
    5.^Kemertelidze E, Sagareishvili T, Syrov V, Khushbaktova Z, Tsutskiridze L, Kurashvili RSaturin - effective vegetative remedy in treatment of type 2 diabetes mellitusGeorgian Med News.(2012 Feb)
    7.^Dapkevicius A, van Beek TA, Lelyveld GP, van Veldhuizen A, de Groot A, Linssen JP, Venskutonis RIsolation and structure elucidation of radical scavengers from Thymus vulgaris leavesJ Nat Prod.(2002 Jun)
    11.^Zheng Q, Sun Z, Zhang X, Yuan J, Wu H, Yang J, Xu XClerodendranoic Acid, a New Phenolic Acid from Clerodendranthus spicatusMolecules.(2012 Nov 19)
    12.^Georgiev M, Pastore S, Lulli D, Alipieva K, Kostyuk V, Potapovich A, Panetta M, Korkina LVerbascum xanthophoeniceum-derived phenylethanoid glycosides are potent inhibitors of inflammatory chemokines in dormant and interferon-gamma-stimulated human keratinocytesJ Ethnopharmacol.(2012 Dec 18)
    13.^Braidy N, Matin A, Rossi F, Chinain M, Laurent D, Guillemin GJNeuroprotective Effects of Rosmarinic Acid on Ciguatoxin in Primary Human NeuronsNeurotox Res.(2013 Oct 5)
    14.^Petersen M, Simmonds MSRosmarinic acidPhytochemistry.(2003 Jan)
    15.^Nakazawa T, Ohsawa KMetabolism of rosmarinic acid in ratsJ Nat Prod.(1998 Aug)
    18.^Baba S, Osakabe N, Natsume M, Yasuda A, Muto Y, Hiyoshi K, Takano H, Yoshikawa T, Terao JAbsorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humansEur J Nutr.(2005 Feb)
    19.^Ritschel WA, Starzacher A, Sabouni A, Hussain AS, Koch HPPercutaneous absorption of rosmarinic acid in the ratMethods Find Exp Clin Pharmacol.(1989 May)
    24.^Tohda Y, Haraguchi R, Kubo H, Muraki M, Fukuoka M, Nakajima SEffects of saiboku-to on dual-phase bronchoconstriction in asthmatic guinea pigsMethods Find Exp Clin Pharmacol.(1999 Jul-Aug)
    26.^Osakabe N, Takano H, Sanbongi C, Yasuda A, Yanagisawa R, Inoue K, Yoshikawa TAnti-inflammatory and anti-allergic effect of rosmarinic acid (RA); inhibition of seasonal allergic rhinoconjunctivitis (SAR) and its mechanismBiofactors.(2004)
    27.^Makino T, Furuta A, Fujii H, Nakagawa T, Wakushima H, Saito K, Kano YEffect of oral treatment of Perilla frutescens and its constituents on type-I allergy in miceBiol Pharm Bull.(2001 Oct)
    28.^Takano H, Osakabe N, Sanbongi C, Yanagisawa R, Inoue K, Yasuda A, Natsume M, Baba S, Ichiishi E, Yoshikawa TExtract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humansExp Biol Med (Maywood).(2004 Mar)
    31.^Domitrović R, Skoda M, Vasiljev Marchesi V, Cvijanović O, Pernjak Pugel E, Stefan MBRosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated miceFood Chem Toxicol.(2013 Jan)
    32.^Ueda H, Yamazaki C, Yamazaki MInhibitory effect of Perilla leaf extract and luteolin on mouse skin tumor promotionBiol Pharm Bull.(2003 Apr)
    34.^Stratton SP, Saboda KL, Myrdal PB, Gupta A, McKenzie NE, Brooks C, Salasche SJ, Warneke JA, Ranger-Moore J, Bozzo PD, Blanchard J, Einspahr JG, Dorr RT, Levine N, Alberts DSPhase 1 study of topical perillyl alcohol cream for chemoprevention of skin cancerNutr Cancer.(2008)
    35.^Stratton SP, Alberts DS, Einspahr JG, Sagerman PM, Warneke JA, Curiel-Lewandrowski C, Myrdal PB, Karlage KL, Nickoloff BJ, Brooks C, Saboda K, Yozwiak ML, Krutzsch MF, Hu C, Lluria-Prevatt M, Dong Z, Bowden GT, Bartels PHA phase 2a study of topical perillyl alcohol cream for chemoprevention of skin cancerCancer Prev Res (Phila).(2010 Feb)