alpha-((3-(3,4-Dihydroxyphenyl)-1-oxo-2-propen-1-yl)oxy)-3,4-dihydroxybenzenepropanoic acid

Rosmarinic acid (RA), a caffeic acid ester, has insulin-sensitizing and antioxidant effects in high fructose-fed model of insulin resistance (IR). This study investigated whether RA supplementation prevents cardiac abnormalities and hypertension in fructose-fed rats (FFR). Rats fed with fructose diet (60 g/100 g) for 60 days exhibited metabolic abnormalities and rise in plasma and cardiac lipids and whole body IR. The levels of cardiac antioxidants and plasma ferric reducing antioxidant power were significantly reduced in FFR concomitant with increased levels of lipid peroxidation and protein oxidation products. A significant rise in troponin T, creatine kinase-MB, aspartate transaminase, and lactate dehydrogenase in plasma of FFR was noted. RA supplementation to FFR (10 mg/kg from the 16th day) significantly improved insulin sensitivity, reduced lipid levels, oxidative damage, and the expression of p22phox subunit of nicotinamide adenine dinucleotide phosphate reduced oxidase, and prevented cardiac hypertrophy. Fructose-induced rise in blood pressure was also lowered by RA through decrease in endothelin-1 and angiotensin-converting enzyme activity and increase in nitric oxide levels. Histology revealed a reduction in myocardial damage in RA-supplemented FFR. These findings suggest that RA acts as a vasoactive substance and a cardioprotector through its antioxidant property. Thus, RA may be useful in reducing the cardiovascular risk associated with IR.

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEP) may be involved in recent increases in lung diseases. DEP has been shown to generate reactive oxygen species. Intratracheal instillation of DEP induces lung inflammation and edema in mice. Rosmarinic acid is a naturally occurring polyphenol with antioxidative and anti-inflammatory activities. /This/ investigated the effects of rosmarinic acid on lung injury induced by intratracheal administration of DEP (500 ug/body) in mice. Oral supplementation with administration of rosmarinic acid (2 mg/body for 3 d) inhibited DEP-induced lung injury, which was characterized by neutrophil sequestration and interstitial edema. DEP enhanced the lung expression of keratinocyte chemoattractant (KC), interleukin-1beta, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha, which was inhibited by treatment with rosmarinic acid. DEP enhanced expression of iNOS mRNA and formation of nitrotyrosine and 8-OHdG in the lung, which was also inhibited by rosmarinic acid. These results suggest that rosmarinic acid inhibits DEP-induced lung injury by the reduction of proinflammatory molecule expression. Antioxidative activities of rosmarinic acid may also contribute to its protective effects.

Rosmarinic acid (RA), a polyphenolic phytochemical, is a natural prolyl oligopeptidase inhibitor. /The present study/ found that RA exerted potent anti-inflammatory effects in in vivo models of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Mice were pretreated with RA one hour before challenge with a dose of 0.5 mg/kg LPS. Twenty-four hours after LPS was given, bronchoalveolar lavage fluid (BALF) was obtained to measure pro-inflammatory mediator and total cell counts. RA significantly decreased the production of LPS-induced TNF-a, IL-6, and IL-1beta compare with the LPS group. When pretreated with RA (5, 10, or 20 mg/kg) the lung wet-to-dry weight (W/D) ratio of the lung tissue and the number of total cells, neutrophils and macrophages in the BALF were decreased significantly. Furthermore, RA may enhance oxidase dimutase (SOD) activity during the inflammatory response to LPS-induced ALI. And /the authors/ further demonstrated that RA exerts anti-inflammation effect in vivo models of ALI through suppresses ERK/MAPK signaling in a dose dependent manner...

The aim of the present work was to study the protective effects of rosmarinic acid against ethanol-induced DNA damage in mice. The antigenotoxic capacity of rosmarinic acid (100 mg/kg) was tested using pre-, co- and post-treatment with ethanol (5 g/kg). Peripheral blood (1 and 24 hr) and brain cells (24 hr) were evaluated using the comet assay and bone marrow was analyzed using the micronucleus assay (24 hr). The results were compared to data of TBARS, enzymes with antioxidant activity, and DCFH-DA test. Peripheral blood and brain cells show that mean damage index (DI) and damage frequency (DF) values of ethanol with pre-treatment with rosmarinic acid group were significantly lower than in the ethanol group. In brain cells all different treatments with ethanol and rosmarinic acid showed significant decrease in DI and DF mean values when compared to ethanol group and negative control. No significant differences were observed in micronucleus frequency, activity of antioxidant enzymes and TBARS between groups. The DCFH-DA test show a reduction of 18% of fluorescence intensity when compare with ethanol group. The results show that rosmarinic acid could decrease the levels of DNA damage induced by ethanol, for both tissues and treatment periods.

For more Interactions (Complete) data for ROSMARINIC ACID (13 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 60(SRC), determined from an estimated log Kow of 1.82(2) and a regression-derived equation appropriate for ionizable compounds(2), indicates that rosmarinic acid is expected to have high mobility in soil(SRC). The estimated pKa of rosmarinic acid is 3.57(3), indicating that this compound will exist partially in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of rosmarinic acid from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.7X10-27 atm-cu m/mole(SRC) using a fragment constant estimation method(2). Rosmarinic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-13 mm Hg at 25 °C(SRC) determined from a fragment constant method(2). Rosmarinic acid has a UV absorption maximum at 332 nm(5); therefore, it may be susceptible to direct photolysis on soil surfaces exposed to sunlight(SRC). Biodegradation data in soil were not available(SRC, 2012).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 60(SRC), determined from a structure estimation method(2), indicates that rosmarinic acid is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.7X10-27 atm-cu m/mole(SRC) developed using a fragment constant estimation method(2). Phenols can undergo sensitized photo-oxidation in surface waters exposed to sunlight via reaction with hydroxyl and RO2 radicals with half-lives on the order of days to weeks at the water surface(4); therefore, photo-oxidation may be an important fate process for rosmarinic acid in natural water(SRC). Rosmarinic acid is expected to undergo hydrolysis in the environment with half-lives of 26 and 2.6 years at pH values of 7 and 8, respectively(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from an estimated log Kow of 1.82(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2012).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), rosmarinic acid, which has an estimated vapor pressure of 1.2X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase rosmarinic acid may be removed from the air by wet and dry deposition(SRC).

Rosmarinic acid is derived from many common herbal plants of the Lamiaceae group: rosemary, sage, spanish sage, oregano, basil, marjoram, thyme, the mint group, lavender, perilla and lemon balm(1).

Concentrations of rosmarinic acid detected in various plants(1).[Table#7331]

Concentrations of rosmarinic acid detected in various plants(1).[Table#7332]

The Koc of rosmarinic acid is estimated as 60(SRC), using an estimated log Kow of 1.82(1) and a regression-derived equation appropriate for an ionizable compound(1). According to a classification scheme(2), this estimated Koc value suggests that rosmarinic acid is expected to have high mobility in soil. The estimated pKa of rosmarinic acid is 3.57(3), indicating that this compound will exist partially in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

Rosemary (Rosmarinus officinalis Linn.) is a common household plant grown in many parts of the world.

Rosmarinic acid is derived from many common herbal plants of the Lamiaceae group: rosemary, sage, spanish sage, oregano, basil, marjoram, thyme, the mint group, lavender, perilla and lemon balm(1).

/HUMAN EXPOSURE STUDIES/ Rosmarinic acid is known to have anti-inflammatory and immunomodulatory activities. This study was performed to evaluate the effect of rosmarinic acid on atopic dermatitis (AD), one of the inflammatory disorders of the skin. Twenty-one subjects (14 women and seven men, 5-28 years of age) with mild AD participated in this study. Rosmarinic acid (0.3%) emulsion was topically applied to the elbow flexures of AD patients twice a day (once in the morning and once in the evening). All subjects were evaluated for skin conditions before treatment at the first visit, and then at 4 and 8 weeks after treatment. According to local Severity Scoring of Atopic Dermatitis index results, erythema on antecubital fossa was significantly reduced at 4 and 8 weeks (P < 0.05). Transepidermal water loss of the antecubital fossa was significantly reduced at 8 weeks compared to before treatment (P < 0.05). ...

/ALTERNATIVE and IN VITRO TESTS/ The protective effects of rosmarinic acid (RA) on H(2)O(2)-induced neurotoxicity in human dopaminergic cell line, SH-SY5Y /were investigated/. Results showed that RA significantly attenuated H(2)O(2)-induced reactive oxygen species (ROS) generation and apoptotic cell death. Rosmarinic acid effectively suppressed the up-regulation of Bax and down-regulation of Bcl-2. Furthermore, RA stimulated the antioxidant enzyme heme oxygenase-1 (HO-1). ... The HO-1 induction by RA was associated with the protein kinase A (PKA) and phosphatidylinositiol-3-kinase (PI3K) signaling pathways. These results suggest that RA can protect SH-SY5Y cells under oxidative stress conditions by regulating apoptotic process...

/ALTERNATIVE and IN VITRO TESTS/ ... This study ... evaluated the cytoprotective effects of two sage extracts (a water and a methanolic extract) against tert-butyl hydroperoxide (t-BHP)-induced toxicity in HepG2 cells. The most abundant phenolic compounds present in the extracts were rosmarinic acid and luteolin-7-glucoside. Both extracts, when co-incubated with the toxicant, protected significantly HepG2 cells against cell death. The methanolic extract, with a higher content of phenolic compounds than the water extract, conferred better protection ... . Both extracts, tested in a concentration that protects 80% against cell death (IC(80)), significantly prevented t-BHP-induced lipid peroxidation and GSH depletion, but not DNA damage assessed by the comet assay...

/ALTERNATIVE and IN VITRO TESTS/ UVA radiation provokes the generation of reactive oxygen species (ROS), which induce oxidative stress in the exposed cells leading to extensive cellular damage and cell death either by apoptosis or necrosis. One approach to protecting human skin against the harmful effects of UV radiation is by using herbal compounds as photoprotectants. This study evaluated the protective effects of Prunella vulgaris L. (Labiatae) and its main phenolic acid component, rosmarinic acid (RA), against UVA-induced changes in a human keratinocyte cell line (HaCaT). Human keratinocytes exposed to UVA (10-30 J/sq cm) were treated with an extract of P. vulgaris (1-75 mg/L) or RA (0.9-18 mg/L) for 4 hr. P. vulgaris and RA exhibited ability to reduce the UVA-caused decrease in a cell viability monitored by neutral red retention and by LDH release into medium. The P. vulgaris extract and RA significantly suppressed UVA-induced ROS production, which manifests as a decrease in intracellular lipid peroxidation, elevation of ATP and reduced glutathione. Post-treatment with P. vulgaris extract and RA also significantly reduced DNA damage. In addition, UVA-induced activation of caspase-3 was inhibited by treatment with P. vulgaris and RA. The P. vulgaris extract and RA demonstrated a concentration-dependent photoprotection (maximum at 25-50 mg/L and 9 mg/L, respectively). These results suggest that P. vulgaris and RA, used in skin care cosmetics, may offer protection against UVA-induced oxidative stress and may be beneficial as a supplement in photoprotective dermatological preparations.

An estimated BCF of 3 was calculated in fish for rosmarinic acid(SRC) using an estimated log Kow of 1.82(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for rosmarinic acid is estimated as 2.7X10-27 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that rosmarinic acid is expected to be essentially nonvolatile from water surfaces(2). Rosmarinic acid's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Rosmarinic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-13 mm Hg(SRC) determined from a fragment constant method(1).

/LABORATORY ANIMALS: Acute Exposure/ The aim of this study was to investigate the therapeutic potential of rosmarinic acid (RA), a natural phenolic, in the treatment of acute liver toxicity. RA at 10, 25 and 50 mg/kg was administered by gavage once daily for 2 consecutive days, 6 hr after carbon tetrachloride (CCl(4)) intoxication. CCl(4) intoxication caused hepatic necrosis and increased serum ALT activity. In the livers, oxidative/nitrosative stress was evidenced by increased 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive substances (TBARS) formation and a significant decrease in Cu/Zn superoxide dismutase (SOD) activity. CCl(4) administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-kappaB), which coincided with the induction of tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase-2 (COX-2). RA improved histological and serum markers of liver damage and significantly ameliorated oxidative/nitrosative stress and inflammatory response in liver tissue. Additionally, RA prevented transforming growth factor-beta1 (TGF-beta1) and alpha-smooth muscle actin (alpha-SMA) expression, suggesting suppression of profibrotic response. Furthermore, RA significantly inhibited the CCl4-induced apoptosis, which was evident from decreased cleavage of caspase-3. The hepatoprotective activity of RA coincided with enhanced NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. The results of this study indicates that RA possesses antioxidant, anti-inflammatory, antiapoptotic and antifibrotic activity against acute liver toxicity.

/LABORATORY ANIMALS: Acute Exposure/ The ... study /evaluated/ the anti-allergic effect of orally administered perilla decoction and to identify the active constituents using mice ear-passive cutaneous anaphylaxis (PCA)-reaction, which is one of the animal models for type I allergy. Perilla decoction significantly suppressed PCA-reaction, and the inhibition % at the dose of 500 mg/kg was 43%. The perilla decoction contains 5.3% of luteolin 7-O-[beta-glucuronosyl(2--)1)beta-glucuronide], 1.6% of apigenin 7-O-[beta-glucuronosyl(2--)1)beta-glucuronide], 0.49% of scutellarin, and 2.5% of rosmarinic acid (weight of compound/dried weight of perilla decoction %), respectively. When these constituents were orally administered to mice at the dose equivalent to 500 mg/kg of perilla decoction, rosmarinic acid and apigenin 7-O-[beta-glucuronosyl(2--)1)beta-glucuronide] significantly suppressed PCA-reaction, and their inhibition % was 41% (p < 0.01) and 32% (p < 0.05), respectively. Since the inhibition % or perilla decoction and rosmarinic acid were nearly equal, the anti-allergic effect of perilla decoction depends primarily on rosmarinic acid. The standard Saiboku-to decoction contained 0.013% of rosmarinic acid, which was too low to exhibit anti-allergic activity in a daily dose of Saiboku-to in adults ...

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The present investigation reports the effect of rosmarinic acid (RA), an antioxidant on gentamicin sulfate (GS)-induced renal oxidative damage in rats. Rosmarinic acid (RA) has been demonstrated to have antioxidant, free radical scavenger and anti-inflammatory effects. Twenty-eight Sprague-Dawley rats were divided in to four equal groups as follows: group 1 (control), group 2 (GS 100 mg/kg/day ip), group 3 (GS 100 mg/kg/day ip + RA 50 mg/kg/day) and group 4 (GS 100 mg/kg/d ip + RA 100 mg/kg/day). Treatments were administrated once daily for 12 days. After 12 days 24 hr urine was collected, blood was sampled and kidneys were removed. Serum and kidney tissue MDA assessed by thiobarbituric acid. Kidney paraffin sections (5 um thickness) from the left kidney stained with periodic acid Schiff. Tubular necrosis was studied semiquantitatively and glomerular volume and volume density of proximal convoluted tubule (PCT) estimated stereologically. Kidney homogenize were prepared from right kidney. Serum creatinine, urea and kidney antioxidant enzymes activity were assessed by special kits. Data were compared by SPSS 13 software and Mann-Whitney test at P < 0.05. Co treatment of GS and RA (High dose) significantly decreased serum creatinine, MDA, urea, tubular necrosis (P < 0.05) and increase renal GSH, GPX, CAT, SOD, volume density of PCT and creatinine clearance significantly in comparison with GS group (P < 0.05). Treatment with RA (high dose) maintained serum creatinine, volume density of PCT, renal GSH, GPX, SOD and MDA as the same level as control group significantly (P < 0.05)...

The rate constant for the vapor-phase reaction of rosmarinic acid with photochemically-produced hydroxyl radicals has been estimated as 1.0X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 4 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). A base-catalyzed second-order hydrolysis rate constant of 8.5X10-3 L/mole-sec(SRC) was estimated using a structure estimation method(2); this corresponds to half-lives of 26 and 2.6 years at pH values of 7 and 8, respectively(2). Rosmarinic acid has UV maximum at 332 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Phenols can undergo sensitized photo-oxidation in surface waters exposed to sunlight via reaction with hydroxyl and RO2 radicals with half-lives on the order of days to weeks at the water surface(4); therefore, photo-oxidation may be an important fate process for rosmarinic acid in natural water(SRC).

Occupational exposure to rosmarinic acid may occur through dermal contact with this compound at workplaces where rosmarinic acid is produced or used. The general population is exposed to rosmarinic acid via ingestion of dietary supplements and foods (herbs) containing rosmarinic acid and dermal contact with this compound in consumer products containing rosmarinic acid. (SRC)

...Rosemary (Rosmarinus officinalis Linn.) is a common household plant grown in many parts of the world. It is used for flavoring food, a beverage drink, as well as in cosmetics; in folk medicine it is used as an antispasmodic in renal colic and dysmenorrhoea, in relieving respiratory disorders and to stimulate growth of hair. Extract of rosemary relaxes smooth muscles of trachea and intestine, and has choleretic, hepatoprotective and antitumerogenic activity. The most important constituents of rosemary are caffeic acid and its derivatives such as rosmarinic acid. These compounds have antioxidant effects. ...

In folk medicine, /rosemary/ is used as an antispasmodic in renal colic and dysmenorrhoea, in relieving respiratory disorders and to stimulate growth of hair.

Used as a food flavoring, beverage, food preservative and as a cosmetic; used in herbal supplements with reported properties including anti-oxidant, anti-inflammatory, anti-viral and use in treating Alzheimer Disease

During an investigation of plant cell cultures that might be useful in the treatment of renal disorders /investigators/ established a vigorously-growing E-4 callus culture of Eritrichium sericeum that produced large amounts of caffeic acid metabolites, (-)-rabdosiin (1.8% dry wt) and rosmarinic acid (4.6% dry wt). Elicitation of the calli by methyl jasmonate induced a 38% increase in total polyphenol production. The most efficient method of eliciting (-)-rabdosiin biosynthesis was through the treatment of E-4 calli with cuprum glycerate, which induced an increase in (-)-rabdosiin production of as much as 4.1% dry wt. ...

One of the major polyphenolic ingredients of Perillae Herba (a leaf of Perilla frutescens), and has an antidepressant-like property in animal models of depression.

Rosemary (Rosmarinus officinalis Linn.) is a common household plant grown in many parts of the world.

Rosmarinic acid is one of the polyphenolic substances contained in culinary herbs such as perilla (Perilla frutescens L.), rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.), mint (Mentha arvense L.), and basil (Ocimum basilicum L.). These herbs are commonly grown in the garden as kitchen herbs, and while used to add flavor in cooking, are also known to have several potent physiological effects.

... The phenolic compound, rosmarinic acid, obtains one of its phenolic rings from phenylalanine via caffeic acid and the other from tyrosine via dihydroxyphenyl-lactic acid. Relatively large-scale production of rosmarinic acid can be obtained from the cell culture of Coleus blumei Benth when supplied exogenously with phenylalanine and tyrosine. Rosmarinic acid is well absorbed from gastrointestinal tract and from the skin. It increases the production of prostaglandin E2 and reduces the production of leukotriene B4 in human polymorphonuclear leucocytes, and inhibits the complement system. It is concluded that rosemary and its constituents especially caffeic acid derivatives such as rosmarinic acid have a therapeutic potential in treatment or prevention of bronchial asthma, spasmogenic disorders, peptic ulcer, inflammatory diseases, hepatotoxicity, atherosclerosis, ischemic heart disease, cataract, cancer and poor sperm motility.

/OTHER TOXICITY INFORMATION/ The influence of elicitation on rosmarinic acid biosynthesis by Lavandula vera MM cell suspension culture was investigated using vanadyl sulfate as an abiotic elicitor. It was established that 12 hr after treatment with 25 mg/L vanadyl sulfate the rosmarinic acid production was increased up to 3.92 g/L (2.8 times higher compared to the control cultivation). No significant amounts of rosmarinic acid were detected in the culture medium in comparison with its intracellular content. However, it was observed that the extracellular content of rosmarinic acid is 3.3 times higher compared to the control variant (4 hr after treatment at elicitor concentration 25 mg/L).