Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice

Domitrović, Robert; Škoda, Marko; Vasiljev, Vanja; Cvijanović, Olga; Pugel, Ester Pernjak; Štefan, Maja Bival

doi:10.1016/j.fct.2012.10.021

Cited by 111 publications

(79 citation statements)

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“…1) Its dried inflorescence and roots have a long history of use in traditional Chinese and European medicine. 2) P. vulgaris has been reported to exhibit numerous pharmacological and biological properties, including antibacterial, 3) anticancer, 4) antihemorrhagic, 5) anti-human immunodeficiency virus (HIV), 6) anti-inflammatory, 7) antioxidant, 8) antiproliferative, 9) antidiabetic, 10) antiviral, 11) hepatoprotective, 12) immunomodulatory, 13) and neuroreparative 3) activities. Chemical investigations have revealed that P. vulgaris contains a variety of bioactive constituents, primarily rosmarinic acid (RA), ursolic acid, and oleanolic acid.…”

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confidence: 99%

Molecular Cloning and Characterization of Genes Involved in Rosmarinic Acid Biosynthesis from <i>Prunella vulgaris</i>

Kim

Shin

Tuấn

et al. 2014

Biological & Pharmaceutical Bulletin

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Prunella vulgaris L., commonly known as "self-heal" or "heal-all," is a perennial herb with a long history of medicinal use. Phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumarate:coenzyme-A (CoA) ligase (4CL) are important enzymes in the phenylpropanoid pathway and in the accumulation of rosmarinic acid (RA), which is a major secondary metabolite in P. vulgaris. In this study, we isolated cDNAs encoding PvPAL, PvC4H, and Pv4CL from P. vulgaris using rapid amplification of cDNA ends polymerase chain reaction (PCR). The amino acid sequence alignments of PvPAL, PvC4H, and Pv4CL showed high sequence identity to those of other plants. Quantitative real-time PCR analysis was used to determine the transcript levels of genes involved in RA biosynthesis in the flowers, leaves, stems, and roots of P. vulgaris. The transcript levels of PvPAL, PvC4H, and Pv4CL1 were the highest in flowers, whereas Pv4CL2 was the highest in roots. High-performance liquid chromatography analysis also showed the highest RA content in the flowers (3.71 mg/g dry weight). We suggest that the expression of the PvPAL, PvC4H, and Pv4CL1 genes is correlated with the accumulation of RA. Our results revealed that P. vulgaris flowers are appropriate for medicinal usage, and our findings provide support for increasing RA production in this plant.

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confidence: 99%

Molecular Cloning and Characterization of Genes Involved in Rosmarinic Acid Biosynthesis from <i>Prunella vulgaris</i>

Kim

Shin

Tuấn

et al. 2014

Biological & Pharmaceutical Bulletin

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“…These results suggest that, through its ROS scavenger activity, RA can block down-stream signaling of EGFR that regulates cell proliferation and migration. This result is not surprising given RA's well-established ability to protect against ROS-mediated effects in a number of tissues and disease states, including protection of the liver from acute oxidative damage [61] and resistance to memory loss in Alzheimer's disease [62]. Exploring RA's effects on H 2 O 2 release is important in this context, because recent discoveries have shown that EGFR signaling results in H 2 O 2 production and oxidation of downstream proteins, and that the direct modification of EGFR by H 2 O 2 at a critical active site cysteine (Cys797), enhances its tyrosine kinase activity [28].…”

Section: Discussionmentioning

confidence: 91%

Rosmarinic Acid Inhibits Cell Growth and Migration in Head and Neck Squamous Cell Carcinoma Cell Lines by Attenuating Epidermal Growth Factor Receptor Signaling

Tumur¹,

Guerra²,

Yanni³

et al. 2015

J Cancer Sci Ther

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Objective: Active components of natural foods are increasingly receiving attention for their chemopreventive and chemotherapeutic potential in a wide variety of cancers. Rosmarinic acid (RA), a phenolic compound in various herbal plants, is well-recognized for its anti-oxidant, anti-inflammatory, anti-proliferative properties in a variety of cell types. In this report, we describe a novel role for RA as an inhibitor of epidermal growth factor (EGF) stimulated signaling in HNSCC and propose a cellular reactive oxygen species (ROS)-mediated mechanism for the observed effects.Methods: Cellular growth, migration and reactive oxygen species (ROS) profiles were examined in RA-treated and untreated HNSCC cell lines (UM-SCC-6 and UM-SCC-10B) using the WST-1 viability assay, established in vitro migration assays, and the CM-H2DCFDA ROS assay, respectively. The influence of RA on EGF-stimulated phosphorylation and its downstream pathways was evaluated using Western-blotting techniques.Results: RA inhibited cell viability, migration and cellular production of ROS in HNSCC cell lines. Furthermore, RA inhibited EGF-induced phosphorylation of the EGFR at tyrosine residues 992 and 845, which led to downregulation of the phosphatidylinositol 3-kinase Akt (PI3K/Akt) and mitogen-activated protein kinase ERK (MAPK/ ERK) pathways.Conclusions: This is the first report describing both growth-and motility-inhibitory roles for RA in HNSCC cells. Additionally, our study is the first to demonstrate that treatment with RA can reduce EGF-induced activation of PI3K/ Akt in tumor cells. The present data suggests that RA holds promise as a chemotherapeutic agent against HNSCC. a novel strategy to down-regulate EGFR signaling using the phenolic compound, rosmarinic acid. RosmarinicActive components of natural foods are increasingly receiving attention for their chemopreventive and chemotherapeutic potential in a wide variety of cancers. One such food component, rosmarinic acid (RA), is a widely distributed phenolic compound in various herbal plants such as rosemary, sweet basil, sage, mint, and perilla (Figure 1) [10,11]. RA is regarded as a daily-consumed safe ingredient, due to its extensive use in the food industry for flavoring, but studies have also elucidated a medicinal role for RA, especially in regard to its anti-oxidant, and anti-inflammatory activities [12,13]. Furthermore, an emerging body of literature has also described the growth inhibitory and anti-invasion properties of RA in colon, skin, breast and ovarian cancers in vitro and/or in vivo [14][15][16][17][18][19], but the mechanisms underlying these effects are poorly understood. A chemopreventive role for RA in HNSCC has been described in 7,12-dimethylbenz (a) anthracene-induced hamster buccal pouch carcinogenesis [20], but a chemotherapeutic role for RA in the treatment of HNSCC has not yet been reported.Given the anti-oxidant properties attributed to RA, it is possible that RA's anti-tumor effects stem from its ability to combat oxidative stress in HNSCC. Oxidative ...

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“…Therefore, components other than carnosol and carnosic acid might contribute to the hepatoprotective effect of RM. Li et al (2010) and Domitrović et al (2013) reported that rosmarinic acid exerted hepatoprotective effects against CCl 4 -induced oxidative stress. The DPPH and H 2 O 2 scavenging activities of rosmarinic acid were reported to be almost equal to those of eriocitrin (Sroka et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of the Antioxidative Activity of Culinary Herbs and Spices, and Hepatoprotective Effects of Three Selected Lamiaceae Plants on Carbon Tetrachloride-Induced Oxidative Stress in Rats

Masuda¹,

Hironaka

Matsui³

et al. 2015

FSTR

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Keywords: culinary herbs and spices, ORAC, peppermint, lemon balm, rosemary, hepatoprotective, carbon tetrachloride IntroductionA state of oxidative stress occurs when there is an excess of reactive species such as reactive oxygen and reactive nitrogen in relation to available antioxidants (Asimov, 2007). Oxidative stress is reported to lead to various diseases such as atherosclerosis, diabetes, inflammatory bowel disease and cancer (Schatz, 2007).Antioxidants synthesized in vivo and taken in from the diet play an important role in defending against reactive species (Reth, 2007).Culinary herbs and spices are sources of dietary antioxidants.These natural materials contain components that differ in properties, e.g., hydrophilic and lipophilic compounds, and function as antioxidants at different reaction rates. Therefore, to evaluate the antioxidative activity of each culinary plant, it is necessary to assay both the hydrophilic and lipophilic fractions.Comparative studies on the antioxidative activities of culinary plants have been reported (Zheng and Wang, 2001;Wu et al., 2004;Ninfali et al., 2005;Shan et al., 2005). However, most of these have focused on hydrophilic compounds, such as polyphenolic compounds and ascorbic acid, and there are few studies on the oxidative activity of both the hydrophilic and lipophilic fractions of plants.The oxygen radical absorbance capacity (ORAC) assay is H. Masuda et al. 408 based on the measurement of antioxidant scavenging activity against peroxyl-radical-induced-oxidation initiated by 2,2-azobis(2-amidino-propane) dihydrochloride (AAPH) at physiological pH (Ou et al., 2001). In addition, the ORAC assay can be performed in both an aqueous solution and a lipophilic environment (Huang et al., 2002(Huang et al., , 2005Prior et al., 2003;. Therefore, this assay is considered to be biologically relevant and suitable for both hydrophilic and lipophilic components in natural materials.In vitro assays such as the ORAC do not measure bioavailability, in vivo stability, and reactivity in situ. Therefore, an in vivo study is useful in confirming whether the administration of potent antioxidants evaluated by the initial in vitro study improves oxidative stress levels.Carbon tetrachloride (CCl 4 )-induced liver injury is an oxidative-stress model used for screening hepatoprotective materials (McCay et al., 1984;Recknagel et al., 1989;Plaa, 2000;Weber et al., 2003 (Deshpande et al., 1998;Sotelo-Félix et al., 2002;Botsoglou et al., 2008;Park, 2010;Farhoudi, 2011). However, in general, many of the phytonutrients in foods that possess biological activities are also unpalatable because of bitter tastes and odors (Drewnoski and Gomez-Carneros, 2000;Lesschaeve and Noble, 2005;Soares et al., 2013). For ease of consumption, improving unfavorable tastes, especially bitterness, and removing undesirable odors in healthy foods is desirable.The objectives of this study were to compare the hydrophilic Materials and MethodsPlant materials Sixty-eight herbs and spices from a variety of countries/re...

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Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice

Cited by 111 publications

References 44 publications

Molecular Cloning and Characterization of Genes Involved in Rosmarinic Acid Biosynthesis from <i>Prunella vulgaris</i>

Molecular Cloning and Characterization of Genes Involved in Rosmarinic Acid Biosynthesis from <i>Prunella vulgaris</i>

Rosmarinic Acid Inhibits Cell Growth and Migration in Head and Neck Squamous Cell Carcinoma Cell Lines by Attenuating Epidermal Growth Factor Receptor Signaling

Comparative Study of the Antioxidative Activity of Culinary Herbs and Spices, and Hepatoprotective Effects of Three Selected Lamiaceae Plants on Carbon Tetrachloride-Induced Oxidative Stress in Rats

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