Effect Of Rosmarinic Acid Research Articles

Effects of rosmarinic acid on oxidative stress parameters in livers and kidneys of sepsis induced wistar albino rats

Effects of rosmarinic acid on oxidative stress parameters in livers and kidneys of sepsis induced wistar albino rats

Assessment of Lemon Balm (Melissa officinalis L.) Hydrogels: Quality and Bioactivity in Skin Cells.

The aim of the study was to design gels with lemon balm extract, assess their quality, and investigate the effect of rosmarinic acid on skin cells in normal conditions and under oxidative stress. Methods. The quantities of rosmarinic acid (RA) released from gels were evaluated by applying the HPLC technique. HaCaT cell viability was assessed by using the MTT method. ROS generation was measured using DCFH-DA dye. The results showed that the gelling material affected the release of RA content from gels. Lower and slower RA content release was determined in carbomer-based gels. After 6 hours of biopharmaceutical research in vitro, at least 4% of RA was released from the gel. The results of the biological studies on HaCaT cells demonstrated that, in the oxidative stress conditions, RA reduced intracellular ROS amounts to 28%; 0.25–0.5 mg/mL of RA increased cell viability by 10–24% and protected cells from the damage caused by H2O2. Conclusions. According to research results, it is appropriate to use a carbomer as the main gelling material, and its concentration should not exceed 1.0%. RA, depending on the concentration, reduces the amount of intracellular ROS and enhances cell viability in human keratinocytes in oxidative stress conditions.

Effects of rosmarinic acid on an experimental model of painful diabetic neuropathy in rats

Context: Diabetic neuropathic (DN) pain is one of the diabetes complications. Rosmarinic acid (RA), a natural phenol antioxidant, shows some biological activities, including anti-inflammatory, analgesic, and anti-diabetic effects.Objectives: We investigated the efficacy of RA administration (10 and 30 mg/kg) on streptozotocin (STZ)-induced neuropathy in rats.Material and methods: The animals received saline or RA (10 and 30 mg/kg, p.o.; once daily) for 8 weeks. DN was evaluated by the tail flick (TF) method, formalin test, and tactile allodynia. At the end, all rats were weighed and underwent plasma glucose measurement.Results: There was an increase in licking time during both formalin test phases in diabetic animals (138.5 ± 10.7 and 448.7 ± 2.6 s) that was decreased by RA10 mg/kg (103.5 ± 7.5 and 284.4 ± 19 s) and RA 30 mg/kg (81.8 ± 11 and 192.7 ± 14 s). RA 30 mg/kg caused anti-nociception during the early phase in treated controls (52.1 ± 6 s) than untreated controls (99.4 ± 5.9 s). The TF latency in diabetics (2.9 ± 0.1 s) was increased in RA10 and 30 mg/kg treated diabetics (5.3 ± 0.4 and 6 ± 0.86 s). The paw withdrawal threshold (PWT) of the diabetics (3.6 ± 0.7 g) was increased after RA 10 and 30 mg/kg (13.8 ± 0.3 and 14 ± 0.4 g) treatment. RA did not induce a significant change in body weight and plasma glucose of rats.Conclusion: RA showed efficacy in amelioration of some aspects of DN. Therefore, RA makes a good candidate for DN treatment in clinical studies.

Protective effect of rosmarinic acid on hypoxia/reoxygenation injury in cardiomyocytes

To study the protective effect of rosmarinic acid (Ros A) on the primary cardiomyocyte hypoxia/reoxygenation (H/R) injury. Primary cardiomyocytes of rats were cultured in vitro to establish the H/R injury of cardiomyocytes and observe the changes in the cell viability and LDH leakage. The changes in ATP content and ROS in cardiomyocytes were measured by using chemiluminescence and fluorescent probe technique. The effects of rosmarinic acid on the apoptosis of cardiomyocytes, cleaved-caspase 3, Akt and p-Akt protein expression were further detected by flow cytometry and western blot analysis. According to the experimental results, Ros A at doses of 25, 50, 100 mg x L(-1) could inhibit the decrease in H/R-induced cell viability, LDH leakage and excessive ROS generation, and maintain the ATP level in cells. Ros A at doses of 50, 100 mg x L(-1) could remarkably inhibit the H/R-induced cardiomyocyte apoptosis and down-regulate the expression of cleaved caspase-3. Moreover, Ros A at doses of 100 mg x L(-1) could significantly up-regulate the expression of p-Akt. Ros A has the significant effect in resisting the cardiomyocyte H/R injury, improve cardiomyocyte energy metabolism and reduce cell apoptosis, which is related to the activation of Akt pathway.

Influence of rosmarinic acid early intervention on the behavior change and the levels of IL-1β and IL-6 in the hippocampus of PTSD model rats

Objective To investigate the effect of rosmarinic acid on the behavioral changes in enhanced single prolonged stress(ESPS) model rats and the levels of interlukin-1β(IL-1β) and interlukin-6(IL-6) in the hippocampus. Methods 48 adult male Sprague Dawley rats were randomly divided into six groups (n=8): Control group, Control+ RA(L) group, Control+ RA(H) group, ESPS group, ESPS+ RA(L)group and ESPS+ RA(H) group.Behavioral changes of these rats were analyzed by open field test and elevated plus-maze.The levels of IL-1β and IL-6 were measured by enzyme linked immunosorbent assay(ELISA). Results (1) Open field test showed that the number of central region entering and the fraction of time exploring in center of ESPS group were significantly reduced than that of Control group((18.13±10.15)times, (26.68±10.06)%) and ESPS+ RA(H) group((16.88±8.81)times, (25.08±8.52)%)(P 0.05). It also showed no significant difference among Control+ RA(L) group, Control+ RA(H) group and Control group.(3) Compared with ESPS group, RA(10mg/kg) reduced the levels of IL-1β and IL-6 in the hippocampus, but RA(5mg/kg) did not have this effect.(4) Correlation analysis results showed the level of IL-1β in the hippocampus was negatively related with the ameliorated PTSD-like behaviors of ESPS exposure rats. Conclusion RA can ameliorate PTSD-like behaviors of ESPS exposure rats, and this effect may be carried out by down-regulating the levels of IL-1β and IL-6 in the hippocampus, especially the IL-1β. Key words: Rosmarinic acid; Posttraumatic stress disorder; Interlukin-1β; Interlukin-6; Rat

Protective Effects of Rosmarinic Acid Against the Developmental Toxicity in Zebrafish Embryos Induced by Cadmium Chloride

Protective Effects of Rosmarinic Acid Against the Developmental Toxicity in Zebrafish Embryos Induced by Cadmium Chloride

Effects of rosmarinic acid on male sex hormones (testosterone-FSH-LH) and testis tissue apoptosis after exposure to electromagnetic field (EMF) in rats

Rosmarinic acid (RA) is a polyphenol 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. It is currently being studied for its effects on Alzheimer's disease and some other diseases. Rosmarinic acid in its natural state as part of a herb has been used to strengthen the memory and to improve mood by dispersing melancholy. Male Wistar rats (n = 40) were allocated to four groups, a control group (n = 10) and three treatment groups (n = 30). The first treatment group received rosmarinic acid (5 mg/kg body weight), the second extract group received rosmarinic acid (5 mg/kg body weight) and electromagnetic field (EMF) exposure at 50 Hz for 40 consecutive days, whilst the forth group received only EMF exposure for 40 consecutive days. Animals were maintained under standard conditions. At the conclusion of the test period, rat testes tissues were removed from all group members and animals were maintained under standard conditions. Tissue preparation was performed and analyzed for apoptosis. There was a significant increase in apoptosis in EMF group and significant increase in testosterone serum level in RA group when compared with other groups (P < 0.05). EMF has negative effect on testis histology in rats. However, these side effects are less seen in the EMF group that received RA. Therefore, it is recommended that usage of rosmarinic acid in modern country has fewer industrial side effects on male fertility. Key words: Apoptosis, electromagnetic field (EMF), male fertility, rosmarinic acid, testis.

The effect of rosmarinic acid on 1,2-dimethylhydrazine induced colon carcinogenesis

This study was carried out to investigate the chemopreventive potential of rosmarinic acid (RA) against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the effect of RA on tumour formation, antioxidant enzymes, cytochrome P450 content, p-nitrophenol hydroxylase and GST activities. Rats were divided into six groups and fed modified pellet diet for the entire experimental period. Group 1 served as control, group 2 received RA (10 mg/kgb.w.). Groups 3-6 were induced colon cancer by injecting DMH (20 mg/kgb.w.) subcutaneously once a week for the first four weeks (groups 3-6). In addition, RA was administered at the doses of 2.5, 5 and 10 mg/kgb.w. to groups 4-6 respectively. DMH treated rats showed large number of colonic tumours; decreased lipid peroxidation; decreased antioxidant status; elevated CYP450 content and PNPH activities; and decreased GST activity in the liver and colon. Supplementation with RA (5 mgkg/b.w.) to DMH treated rats significantly decreased the number of polyps (50%); reversed the markers of oxidative stress (21.0%); antioxidant status (38.55%); CYP450 content (29.41%); and PNPH activities (21.9%). RA at the dose of 5 mg/kgb.w. showed a most pronounced effect and could be used as a possible chemopreventive agent against colon cancer.

アレルギー性鼻炎モデルラットに対するロズマリン酸の効果

アレルギー性鼻炎モデルラットに対するロズマリン酸の効果

Effect of Rosmarinic Acid on Experimental Diabetic Nephropathy

Connective tissue growth factor (CTGF) plays a pathogenic role in diabetic nephropathy (DN). Rosmarinic acid (RA) is a naturally occurring phenolic acid. This study was conducted to investigate the efficacy of RA on DN and to elucidate the potential mechanism. High glucose (HG)-stimulated cultured human renal proximal tubular epithelial cells (HK-2) analysed CTGF expression by western blotting, and it was investigated whether extracellular signal-regulated kinase (ERK) signalling pathway was involved. Using streptozotocin (STZ)-induced rat animal models, diabetic rats were randomized to receive intragastric (i.g.) doses of RA. Renal tissue, blood and urine samples were collected to determine biochemical index and analyse protein expression. In vitro study, RA reduced CTGF excretion in HG-induced HK-2 cells through the ERK signalling pathway. In an in vivo study, I.g. of RA 7.5 or 15 mg/kg significantly ameliorated renal function and increased body-weight. Meanwhile, RA reduced renal CTGF expression by immunohistochemical staining and reduced serum levels of CTGF. Besides, there were no significant differences in glycaemia levels between the RA groups compared with the STZ-treated group. Furthermore, RA ameliorated renal pathology. These results suggest that RA exerts an early renal protective role to DN. Inhibition of CTGF may be a potential target in DN therapy, which highlights the possibility of using RA in the treatment of DN.

Anti-inflammatory Properties of Clovamide and Theobroma cacao Phenolic Extracts in Human Monocytes: Evaluation of Respiratory Burst, Cytokine Release, NF-κB Activation, and PPARγ Modulation

There is a great interest in the potential health benefits of biologically active phenolic compounds in cocoa (Theobroma cacao) and dark chocolate. We investigated the anti-inflammatory potential of clovamide (a N-phenylpropenoyl-L-amino acid amide present in cocoa beans) and two phenolic extracts from unroasted and roasted cocoa beans, by evaluating superoxide anion (O(2)(-)) production, cytokine release, and NF-κB activation in human monocytes stimulated by phorbol 12-myristate 13-acetate (PMA). The effects of rosmarinic acid are shown for comparison. Clovamide and rosmarinic acid inhibited PMA-induced O(2)(-) production and cytokine release (with a bell-shaped curve and maximal inhibition at 10-100 nM), as well as PMA-induced NF-κB activation; the two cocoa extracts were less effective. In all tests, clovamide was the most potent compound and also enhanced peroxisome proliferator-activated receptor-γ (PPARγ) activity, which may exert anti-inflammatory effects. These findings indicate clovamide as a possible bioactive compound with anti-inflammatory activity in human cells.

Ex vivo protective effect of rosmarinic acid and Mentha×villosa water extract on tissue injury induced by ischaemia/reperfusion

Ex vivo protective effect of rosmarinic acid and Mentha×villosa water extract on tissue injury induced by ischaemia/reperfusion

Anti‐invasion effect of rosmarinic acid via the extracellular signal‐regulated kinase and oxidation–reduction pathway in Ls174‐T cells

Rosmarinic acid is a major phenylpropanoid isolated from Prunella vulgaris L., which is a composition of herbal tea for centuries in China. However, the anti-invasion activity on Ls174-T human colon carcinoma cells has not been studied. In this study, we investigated the anti-metastasis functions according to wound healing assay, adhesion assay, and Transwell assay and found that rosmarinic acid could inhibit migration, adhesion, and invasion dose-dependently. Rosmarinic acid also could decrease the level of reactive oxygen species by enhancing the level of reduced glutathione hormone. In addition, rosmarinic acid repressed the activity and expression of matrix metalloproteinase-2,9. According to Western blot and quantitative real-time PCR assay, rosmarinic acid may inhibit metastasis from colorectal carcinoma mainly via the pathway of extracellular signal-regulated kinase. In animal experiment, intraperitoneal administration of 2 mg of rosmarinic acid reduced weight of tumors and the number of lung nodules significantly compared with those of control group. Therefore, these results demonstrated that rosmarinic acid can effectively inhibit tumor metastasis in vitro and in vivo.

Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease affecting motor neurons. About 2% of patients with the disease are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). The purpose of this study is to assess the effect of rosemary extract and its major constituents, rosmarinic acid (RA) and carnosic acid (CA), in human SOD1 G93A transgenic mice, which are well-established mouse models for ALS. The present study demonstrates that intraperitoneal administration of rosemary extract or RA from the presymptomatic stage significantly delayed motor dysfunction in paw grip endurance tests, attenuated the degeneration of motor neurons, and extended the life span of ALS model mice. In addition, RA administration significantly improved the clinical score and suppressed body weight loss compared with a vehicle-treated group. In conclusion, this study provides the first report that rosemary extract and, especially, RA have preventive effects in the mouse model of ALS.

Antioxidation Effects of Rosmarinic Acid on Human Skin Melanoma Cells Treated with Hydrogen Peroxide

The purpose of this study was to evaluate the antioxidant effect of rosmarinic acid on the cultured human skin melanoma cells injured by reactive oxygen species. The cytotoxicity and antioxidant effect were analyzed by XTT assay for cell adhesion activity, DPPH-radical scavenging activity, lactate dehydrogenase (LDH) activity after treated of cells with or without hydrogen peroxide (H2O2) for 1–10 h. H2O2 decreased the cell adhesion activity in cultured human melanoma cells in a dose- and time-dependent manner after cells were treated with 20–110 ώM of H2O2 for 5–7 h. IC50 values of H2O2 by XTT assay were 90 ώM, respectively. H2O2 increased LDH activity dose dependently. LDH50 was determined at 60 ώM H2O2 after treatment of cells with 50–90 ώM H2O2 for 8 h. Rosmarinic acid increases cell adhesion activity, DPPH-radical scavenging and decreases LDH activity. The treatment of the cells with H2O2 shows highly toxic effects on cultured human skin melanoma cells. Rosmarinic acid increases cell adhesion activity, DPPH-radical scavenging activity and decreases LDH activity in the cells treated with H2O2. It is considered that rosmarinic acid shows antioxidant effect on ROS such as H2O2.

Anti‐inflammatory effect of Rosmarinic acid on a model of carrageenan‐induced paw edema

Rosmarinic acid (RA) is a naturally occurring polyphenolic compound with strong antioxidant capacity that has been shown to inhibit the expression of NF‐¿B promoter‐related genes. Here we evaluated the anti‐inflammatory properties of RA and its protective effects in three experimental models of inflammation. In order to study the effects of RA in local inflammation, a carrageenan‐induced paw edema model in rats was performed. RA was administered at 10, 25 or 50 mg/kg (p.o.), 30 minutes before carrageenan injection. Inflammation was assessed by measurement of paw volume increase after 6h. 46 male Wistar rats (100‐150g) were randomly allocated into six groups as described: Control n=8, Carrageenan n=10, RA10 n=8, RA25 n=8, RA50 n=8, Indomethacin n=4). Results demonstrate that administration of RA at the dose of 25 mg/kg can reduce paw edema by over 20%, and it exhibits a dose‐response effect. Anti‐oxidant activity and inhibition of cytokine release was accessed by the use of cellular injury models, which confirmed the protective effect observed on the in vivo model of local inflammation. Therefore, we demonstrate here that rosmarinic acid causes a substantial reduction of inflammation on both in vitro and in vivo models. We propose that rosmarinic acid and similar phenolic compounds may be useful in the therapy of inflammation‐related injury.

Phytochemistry and antimicrobial compounds of Hymenocrater calycinus

The genus, Hymenocrater, belongs to the plant family Lamiaceae which contains eleven shrub species, of which H. calycinus belonges and grows wildly in Northeastern Iran. From the ethyl acetate and methanol extracts of the flowered aerial parts of Hymenocrater calycinus, four compounds were isolated using chromatographic methods and identified by spectroscopic data (MS, 1 H- and 13 C-NMR, HMQC, HMBC and 1 H- 1 H COSY). The effect of rosmarinic acid, as the main component in our study was applied to Staphylococcus aureus, Escherichia coli, Candida albicans and Aspergillus niger by the broth dilution method. Isolated compounds were identified as s-sitosterol (1), ursolic acid (2), rosmarinic acid (3) and quercetin-3-O- rutinoside (4). The results of our assay against bacteria and fungi show that, rosmarinic acid has an antifungal property against Candida albicans (MIC, 250 μg mL -1 ).

Effects of Rosemary Extracts on the Reduction of Heterocyclic Amines in Beef Patties

ABSTRACT: The effects of rosmarinic acid and a rosemary antioxidant powder were evaluated on the reduction and mutagenicity of MeIQx, PhIP, and comutagens norharman and harman in beef patties fried at 375 °F for 5 min each side and 400 °F for 7.5 min each side. Both rosemary extracts were found to effectively decrease the formation and overall mutagenic activity of heterocyclic amines (HCAs) due to their antioxidative characteristics. At the lower temperature, rosmarinic acid was able to reduce MeIQx by up to 64% and PhIP by 48%, while rosemary powder reduced the formations of MeIQx up to 69% and PhIP up to 66%. The effects of the rosemary extracts were more dramatic when cooking temperature and time were increased, as rosmarinic acid was able to reduce MeIQx formation up to 70% and PhIP up to 64%; also, rosemary powder significantly reduced MeIQx up to 57% and PhIP up to 77%. The overall mutagenic activity was evaluated by the Ames Salmonella assay and both rosemary extracts were capable of reducing mutagenicity in beef patties at the higher cooking temperature of 400 °F. At 375 °F there was an insignificant trend of the rosemary extracts decreasing the number of Salmonella revertants. There was no significant inhibiting effect by any of the rosemary extracts on the formation of either norharman and harman as measured in this study.

Anti‐inflammatory and anti‐allergic effect of rosmarinic acid (RA); inhibition of seasonal allergic rhinoconjunctivitis (SAR) and its mechanism

The present study was undertaken to determine whether oral supplementation with rosmarinic acid (RA) is an effective intervention for patients with SAR. In addition, the anti-inflammatory mechanism of RA also estimated in the ear edema models. Patients were treated daily with RA (200 mg or 50 mg) or placebo for 21 days. Patients recorded symptoms daily and profiles of infiltrating cells and concentration of cytokines were measured in nasal lavage fluid. Compared to placebo, supplementation with RA resulted in a significant decrease in responder rates for each symptom. RA also significantly decreased the numbers of neutrophils and eosinophils in nasal lavage fluid. Topical application RA showed anti-inflammatory activity 5-hours after 12-tetradecanoylphorbol 13-acetate (TPA) treatment with marked inhibition of neutrophil infiltration. Up regulation of ICAM-1, VCAM-1 cyclooxygenase-2 (COX-2), KC and MIP-2 by TPA were markedly reduced by pre-treatment with extract of perilla (PE) or RA. Reactive oxygen radical production detected as thiobarbituric acid reactive substance (TBARS), lipid peroxide (LPO) and 8-hydroxy-2'deoxyguanosine (8OH-dG), by double treatment of TPA was reduced by pretreatment with PE or RA. RA is an effective intervention for SAR that is mediated by inhibition of PMNL infiltration. This effect of RA is due to two independent mechanisms: inhibition of the inflammatory response and scavenging of ROS.