Rosmarinic Acid

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 from. It is a general anti-oxidant and health compound, and seen as 'healthy'.

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Rosmarinic acid is a plant-based compound found in a wide variety of spices, but most well known for being the active ingredient in Rosemary and Perilla Oil.

It displays general anti-oxidant and anti-inflammatory effects, and may protect against various forms of cancers. Additionally, it can be absorbed through the skin when in an ethanol base (typically perillyl alcohol).

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Also Known As

Rosmarinus Officinalis Extract, Rosemary Extract, Perilla Frutescens extract. Perilla Extract


Do Not Confuse With

Rosemary (the plant), Rosa damascena, Roselle, Rhodiola Rosea, Perilla Oil (a major source)


Goes Well With

  • Lycopene (in regards to prevention of LDL oxidation)
  • Alcohol (for topical absorption)

Stacks Part Of increased usefulness


Caution Notice

Examine.com Medical Disclaimer

A standard dose is 200-300mg active Rosmarinic acid (check source for extract percentage) for oral ingestion.


The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Rosmarinic Acid has in your body, and how strong these effects are.
GradeLevel of Evidence
ARobust research conducted with repeated double blind clinical trials
BMultiple studies where at least two are double-blind and placebo controlled
CSingle double blind study or multiple cohort studies
DUncontrolled or observational studies only
Level of Evidence
EffectChange
Magnitude of Effect Size
Scientific ConsensusComments
CNasal Congestion

Minor

Nasal congestion is reduced secondary to reducing pollen allergies

CAllergies

Minor

Rosmarinic acid appears to be effective in suppressing the response to pollen allergies in persons with seasonal rhinitus

DSymptoms of Atopic dermatitis

Minor

Topical application of rosmarinic acid may aid symptoms of atopic dermatitis


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Table of Contents:


Edit1. Sources and structure

1.1. Sources

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

1.2. Structure

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]


Edit2. Pharmacology

2.1. Serum

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.

2.2. 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]


Edit3. Cardiovascular Health

3.1. Endothelium

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]


Edit4. Inflammation and Immunology

Rosmarinic acid is being investigated for its interactions with inflammation and immunology due to it being an ingredient of Perilla Oil, and the plant the oil is derived from (Perilla frutescens Britton) being a component of the Kampo (Traditional Japanese) medicine known as Saiboku-To which is demonstrated effective against allergies.[22][23][24]

4.1. Mechanisms

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]

4.2. 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]

4.3. 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


Edit5. 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]


Edit6. Interactions with Organ Systems

6.1. Liver

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]


Edit7. Interactions with Cancer Metabolism

7.1. Skin

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]

References

  1. Lee JH, et al. Identification, characterisation, and quantification of phenolic compounds in the antioxidant activity-containing fraction from the seeds of Korean perilla (Perilla frutescens) cultivars. Food Chem. (2013)
  2. Makino T, et al. Inhibitory effect of decoction of Perilla frutescens on cultured murine mesangial cell proliferation and quantitative analysis of its active constituents. Planta Med. (2001)
  3. al-Sereiti MR, Abu-Amer KM, Sen P. Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials. Indian J Exp Biol. (1999)
  4. Flavonoids and Phenolic Acids of Sage: Influence of Some Agricultural Factors
  5. Kemertelidze E, et al. Saturin - effective vegetative remedy in treatment of type 2 diabetes mellitus. Georgian Med News. (2012)
  6. Biogenesis of rosmarinic acid in Mentha
  7. Dapkevicius A, et al. Isolation and structure elucidation of radical scavengers from Thymus vulgaris leaves. J Nat Prod. (2002)
  8. Rosmarinic acid and related phenolics in hairy root cultures of Ocimum basilicum
  9. Hakkim FL, Shankar CG, Girija S. Chemical composition and antioxidant property of holy basil (Ocimum sanctum L.) leaves, stems, and inflorescence and their in vitro callus cultures. J Agric Food Chem. (2007)
  10. Malahubban M, et al. Phytochemical analysis of Andrographis paniculata and Orthosiphon stamineus leaf extracts for their antibacterial and antioxidant potential. Trop Biomed. (2013)
  11. Zheng Q, et al. Clerodendranoic Acid, a New Phenolic Acid from Clerodendranthus spicatus. Molecules. (2012)
  12. Georgiev M, et al. Verbascum xanthophoeniceum-derived phenylethanoid glycosides are potent inhibitors of inflammatory chemokines in dormant and interferon-gamma-stimulated human keratinocytes. J Ethnopharmacol. (2012)
  13. Braidy N, et al. Neuroprotective Effects of Rosmarinic Acid on Ciguatoxin in Primary Human Neurons. Neurotox Res. (2013)
  14. Petersen M, Simmonds MS. Rosmarinic acid. Phytochemistry. (2003)
  15. Nakazawa T, Ohsawa K. Metabolism of rosmarinic acid in rats. J Nat Prod. (1998)
  16. Baba S, et al. Orally administered rosmarinic acid is present as the conjugated and/or methylated forms in plasma, and is degraded and metabolized to conjugated forms of caffeic acid, ferulic acid and m-coumaric acid. Life Sci. (2004)
  17. Nakazawa T, Ohsawa K. Metabolites of orally administered Perilla frutescens extract in rats and humans. Biol Pharm Bull. (2000)
  18. Baba S, et al. Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans. Eur J Nutr. (2005)
  19. Ritschel WA, et al. Percutaneous absorption of rosmarinic acid in the rat. Methods Find Exp Clin Pharmacol. (1989)
  20. Wang L, Sweet DH. Competitive inhibition of human organic anion transporters 1 (SLC22A6), 3 (SLC22A8) and 4 (SLC22A11) by major components of the medicinal herb Salvia miltiorrhiza (Danshen). Drug Metab Pharmacokinet. (2012)
  21. Rosmarinic acid: A new inhibitor of complement C3-convertase with anti-inflammatory activity
  22. Egashira Y, Nagano H. A multicenter clinical trial of TJ-96 in patients with steroid-dependent bronchial asthma. A comparison of groups allocated by the envelope method. Ann N Y Acad Sci. (1993)
  23. Nakajima S, et al. Effect of saiboku-to (TJ-96) on bronchial asthma. Induction of glucocorticoid receptor, beta-adrenaline receptor, IgE-Fc epsilon receptor expression and its effect on experimental immediate and late asthmatic reaction. Ann N Y Acad Sci. (1993)
  24. Tohda Y, et al. Effects of saiboku-to on dual-phase bronchoconstriction in asthmatic guinea pigs. Methods Find Exp Clin Pharmacol. (1999)
  25. Kimura Y, et al. Studies on the activities of tannins and related compounds, X. Effects of caffeetannins and related compounds on arachidonate metabolism in human polymorphonuclear leukocytes. J Nat Prod. (1987)
  26. Osakabe N, et al. Anti-inflammatory and anti-allergic effect of rosmarinic acid (RA); inhibition of seasonal allergic rhinoconjunctivitis (SAR) and its mechanism. Biofactors. (2004)
  27. Makino T, et al. Effect of oral treatment of Perilla frutescens and its constituents on type-I allergy in mice. Biol Pharm Bull. (2001)
  28. Takano H, et al. Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. Exp Biol Med (Maywood). (2004)
  29. Superoxide Scavenging Activity of Rosmarinic Acid from Perilla frutescens Britton Var. acuta f. viridis
  30. Fuhrman B, et al. Lycopene synergistically inhibits LDL oxidation in combination with vitamin E, glabridin, rosmarinic acid, carnosic acid, or garlic. Antioxid Redox Signal. (2000)
  31. Domitrović R, et al. Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice. Food Chem Toxicol. (2013)
  32. Ueda H, Yamazaki C, Yamazaki M. Inhibitory effect of Perilla leaf extract and luteolin on mouse skin tumor promotion. Biol Pharm Bull. (2003)
  33. Osakabe N, et al. Rosmarinic acid inhibits epidermal inflammatory responses: anticarcinogenic effect of Perilla frutescens extract in the murine two-stage skin model. Carcinogenesis. (2004)
  34. Stratton SP, et al. Phase 1 study of topical perillyl alcohol cream for chemoprevention of skin cancer. Nutr Cancer. (2008)
  35. Stratton SP, et al. A phase 2a study of topical perillyl alcohol cream for chemoprevention of skin cancer. Cancer Prev Res (Phila). (2010)
  36. Lee J, et al. Effect of rosmarinic acid on atopic dermatitis. J Dermatol. (2008)

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