Structure of Rosmarinic acid
CAS No.: 20283-92-5
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Rosmarinic acid is a naturally occurring polyphenol with antioxidative and anti-inflammatory activities.
Synonyms: Labiatenic acid; Rosemary acid; NPLC 0542
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Aydin, Merve ; Unusan, Nurhan ; Sumlu, Esra ; Korucu, Emine Nedime ;
Abstract: Candida species, opportunistic pathogens that cause various infections, pose a significant threat due to their ability to form biofilms that resist antifungal treatments and immune responses. The increasing resistance of Candida spp. and the limited availability of effective treatments have prompted the research of natural compounds as alternative therapies. This study assessed the anti-fungal properties of RA against Candida species, focusing on its impact on C. albicans biofilms and the underlying mechanisms. The antifungal efficacy of RA was evaluated using the CLSI M27-A3 microdilution method on both fluconazole-susceptible and -resistant strains. Biofilm formation by C. albicans was assessed through a crystal violet assay, while its antibiofilm activity was analyzed using an MTT assay and field emission scanning electron microscopy (FESEM). Gene expression related to biofilm formation was studied using quantitative real-time PCR (qRT-PCR), and statistical analysis was performed with an ANOVA. Among the 28 Candida strains tested, RA exhibited minimum inhibitory concentration (MIC) values ranging from 160 to 1280 µg/mL. At a 640 µg/mL concentration, it significantly reduced the expression of genes associated with adhesion (ALS3, HWP1, and ECE1), hyphal development (UME6 and HGC1), and hyphal cAMP-dependent protein kinase regulators (CYR1, RAS1, and EFG1) in RAS1-cAMP-EFG1 pathway (p < 0.05). FESEM analysis revealed a reduction in hyphal networks and disruptions on the cell surface. Our study is the first to demonstrate the effects of RA on C. albicans adhesion, hyphae development, and biofilm formation through gene expression analysis with findings supported by FESEM. This approach distinguishes our study from previous studies on the effect of RA on Candida. However, the high MIC values of RA limit its antifungal potential. Therefore, more extensive research using innovative methods is required to increase the antifungal effect of RA.
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Keywords: rosmarinic acid ; Candida albicans ; antifungal activity ; biofilm-related genes ; FESEM
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Enhancing the anticancer effects of Apiaceae spice phytochemicals.
Scott, Jared Lee ;
Abstract: Breast cancer (BC) is the second greatest contributor to the death of women, second only to heart disease, and is the most common type of cancer. BC treatments involve the administration of adjuvant chemotherapies which often have side effects that prevent patients from completing the full course of drugs or the refusal to take these potentially lifesaving treatments. Many chemotherapy drugs are developed from plants, and some plant extracts can exhibit significant anticancer activities while also having less toxic side effects. However, these potential "plant therapeutics" suffer from poor oral bioavailability. The Apiaceae plant family consists of several species that are used as culinarily spices including anise, celery, cumin, and coriander, all of which have demonstrated antioxidant, chemopreventive, and anticancer activities. One method to improve the systemic distribution of anticancer phytochemicals is their encapsulation in naturally produced membrane bound nanoparticles known as exosomes. Exosomes are produced by most eukaryotic organisms, as well as some prokaryotes, and are involved in cell-to-cell communication through the delivery of proteins, nucleic acids, and small molecules from one cell to another. Exosomes are found in many extracellular fluids including blood, urine, and milk. Bovine milk exosomes represent a scalable source of exosomes that are already present in the human diet and have been explored as a drug delivery system that can increase effectiveness and improve bioavailability. To enhance the loading potential and anticancer bioactivity of Apiaceae phytochemicals, an acid hydrolysis (AH) of the glycoside compounds present in ethanolic spice extracts was performed on eight ethanolic spice extracts. The antiproliferative effects of AH extracts and exosomal formulations were assayed with three model types of BC cells. Cumin was characterized in greater detail as these extracts had the highest concentration of terpenoids and alkaloids while also having significant concentrations of phenolics and responded well to AH with increased antiproliferative activity and exosomal loading. Extracts and exosomal formulations exhibited broad antiproliferative effects with lower IC50s in the extracts delivered with exosomes. The phytochemical contents of AH-cumin extracts and exosomal formulations were assayed with HPLC-DAD, LC-MS/MS, and GC-MS, while the potential anticancer mechanisms of these treatments were investigated in triple negative BC (TNBC). AHcumin extracts were determined to have numerous phenolic compounds, many of which have known anticancer mechanisms, in addition to several alkaloids and lipid compounds, some of which have activities that could contribute to the anticancer effects observed. Mechanistically, AH-cumin extracts and exosomal formulations were shown to interact with multidrug resistance proteins and inhibit lipid metabolism in TNBC cells. These results indicate that acid hydrolyzed cumin extracts delivered through exosome nanoparticles represent a possible avenue towards the development of novel treatments for TNBC, the hardest type of BC to treat.
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Discovery of Polyphenolic Natural Products as SARS-CoV-2 Mpro Inhibitors for COVID-19
Krueger, Nadine ; Kronenberger, Thales ; Xie, Hang ; Rocha, Cheila ; Poehlmann, Stefan ; Su, Haixia , et al.
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chem. phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a variety of natural products for their ability to inhibit SARS-CoV-2 Mpro. Several compounds were discovered to inhibit Mpro at low micromolar concentrations It was possible to crystallize robinetin together with SARS-CoV-2 Mpro, and the X-ray structure revealed covalent interaction with the protease's catalytic Cys145 site. Selected potent mols. also exhibited antiviral properties without cytotoxicity. Some of these powerful inhibitors might be utilized as lead compounds for future COVID-19 research.
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Keywords: COVID-19 ; antivirals ; coronavirus ; covalent drugs ; dynamic light scattering ; inhibitors ; main protease ; natural products
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Purchased from AmBeed: 20554-84-1 ; 18524-94-2 ; 568-73-0 ; 989-51-5 ; 484-12-8 ; 86404-04-8 ; 491-70-3 ; 2752-65-0 ; 6147-11-1 ; 10083-24-6 ; 50-81-7 ; 2752-65-0 ; 522-12-3 ; 529-44-2 ; 529-53-3 ; 546-43-0 ; 501-36-0 ; 28957-04-2 ; 4674-50-4 ; 477-43-0 ; 553-21-9 ; 96829-58-2 ; 96574-01-5 ; 20283-92-5 ; 490-31-3 ; 17912-87-7 ; 520-31-0 ; 86404-04-8
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CAS No. : | 20283-92-5 |
Formula : | C18H16O8 |
M.W : | 360.31 |
SMILES Code : | O=C(O)[C@H](OC(/C=C/C1=CC=C(O)C(O)=C1)=O)CC2=CC=C(O)C(O)=C2 |
Synonyms : |
Labiatenic acid; Rosemary acid; NPLC 0542
|
MDL No. : | MFCD00017740 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
In Vitro:
Concentration | Treated Time | Description | References |
Escherichia coli (KRX) | 1000 µM | 10 hours | No significant inhibition of E. coli growth | Int J Mol Sci. 2021 Dec 1;22(23):13010 |
Escherichia coli (BL21(DE3)) | 1000 µM | 10 hours | No significant inhibition of E. coli growth | Int J Mol Sci. 2021 Dec 1;22(23):13010 |
Rat cerebrocortical nerve terminals (synaptosomes) | 1–50 µM | 10 minutes | To investigate the effect of rosmarinic acid on glutamate release, it was found that rosmarinic acid inhibited 4-AP-induced glutamate release in a concentration-dependent manner with an IC50 of 11 μM and maximum inhibition of 48.8±2.5%. | Biomolecules. 2021 Jul 15;11(7):1029 |
Neonatal rat heart cardiac fibroblasts (CFs) | 30μg/mL | 16 hours | To evaluate the effect of rosmarinic acid on Fas L expression and release in fibroblasts induced by doxorubicin, results showed that RA pretreatment significantly inhibited the expression and release of Fas L. | Int J Biol Sci. 2019 Jan 1;15(3):556-567 |
Neonatal rat cardiomyocytes (CMs) | 20μg/mL | 16 hours | To evaluate the protective effect of rosmarinic acid on doxorubicin-induced cardiomyocyte apoptosis, results showed that RA pretreatment had almost negligible beneficial effect on DOX directly induced cardiomyocyte apoptosis. | Int J Biol Sci. 2019 Jan 1;15(3):556-567 |
Mouse proximal tubular epithelial cells | 40 µM | 24 hours | Rosmarinic acid significantly attenuated CdCl2-induced cytotoxicity, restored cell viability, and inhibited oxidative stress and apoptosis. | Int J Mol Sci. 2019 Apr 24;20(8):2027 |
Mouse splenocytes | 0, 10, 30, 100 µg/mL | 24 hours | To evaluate the effect of rosmarinic acid on Con A-induced Th1/2/17 cytokine levels in mouse splenocytes. Results showed that rosmarinic acid significantly inhibited the production of Th1 (IFN-γ and TNF-α), Th2 (IL-4, IL-5, and IL-13), and Th17A cytokines. | Int J Mol Sci. 2024 Nov 27;25(23):12737 |
HaCaT cells | 100 µg/mL | 24 hours | To evaluate the effect of rosmarinic acid on IFN-γ/TNF-α-induced chemokine levels in HaCaT cells. Results showed that rosmarinic acid significantly reduced the levels of RANTES, TARC, eotaxin, and MIP-1α. | Int J Mol Sci. 2024 Nov 27;25(23):12737 |
SH-SY5Y cells | 100 µM | 24 hours | To evaluate the protective effect of rosmarinic acid against rotenone-induced toxicity in SH-SY5Y cells. Results showed that rosmarinic acid significantly restored cell viability, reduced apoptosis, and restored normal cell morphology. | Nutrients. 2022 Aug 26;14(17):3508 |
SH-SY5Y cells | 0.2% v/v | 24 hours | Assess neuroprotective effects against Aβ42-induced toxicity; both RA and ROE significantly reduced cell death, with ROE being slightly more effective. | Antioxidants (Basel). 2024 Nov 19;13(11):1419 |
Monocytes (THP-1) | 1, 10, 50, 100 µM | 24 hours | Rosmarinic acid significantly reduced oxLDL-induced monocyte adhesion and transmigration under high glucose conditions. | Int J Mol Med. 2022 May;49(5):68 |
Endothelial cells (EA.hy926) | 1, 10, 50, 100 µM | 24 hours | Rosmarinic acid significantly reversed oxLDL-induced overexpression of ICAM-1 and VCAM-1, and monocyte-EC adhesion under high glucose conditions. | Int J Mol Med. 2022 May;49(5):68 |
Normal human epidermal keratinocytes (NHEKs) | 2 μg/mL and 4 μg/mL | 24 hours | To evaluate the effect of rosmarinic acid on NHE1 mRNA expression. Results showed that 4 μg/mL rosmarinic acid significantly increased the NHE1/GAPDH ratio (134.6±5.6%). | Int J Mol Sci. 2022 Mar 31;23(7):3910 |
THP-1 macrophages | 1, 10, 50, 100 µM | 24 hours | To evaluate the effect of RA on oxLDL-induced lipid accumulation. RA significantly reduced oxLDL-induced lipid accumulation in THP-1 macrophages under high glucose (HG) conditions. | Int J Mol Sci. 2021 Aug 16;22(16):8791 |
Normal human astrocyte (NHA) cells | 0, 100, 200, 400 µM | 24 or 48 hours | RA did not significantly affect the viability and morphology of NHA cells. | Int J Mol Med. 2021 May;47(5):67 |
U343 glioma cells | 0, 100, 200, 400 µM | 24 or 48 hours | RA significantly suppressed the proliferation, migration, and invasion of U343 cells and induced apoptosis. RA also reduced the expression levels of MMP-2 and MMP-9, increased the expression of Bax and cleaved caspase-3, and decreased the expression of Bcl-2. | Int J Mol Med. 2021 May;47(5):67 |
U251 glioma cells | 0, 100, 200, 400 µM | 24 or 48 hours | RA significantly suppressed the proliferation, migration, and invasion of U251 cells and induced apoptosis. RA also reduced the expression levels of MMP-2 and MMP-9, increased the expression of Bax and cleaved caspase-3, and decreased the expression of Bcl-2. | Int J Mol Med. 2021 May;47(5):67 |
MC38 cells | 50, 100, 150 µM | 30 hours | Inhibited migration and invasion of MC38 cells | Acta Pharmacol Sin. 2024 Jan;45(1):193-208. |
A549DDP cells | 0-200 μg/mL | 48 hours | Rosmarinic acid significantly inhibited NSCLC cell proliferation and cell colony formation in a dose-dependent manner, induced G1 phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to DDP. | Phytother Res. 2020 May;34(5):1142-1153 |
A549 cells | 0-200 μg/mL | 48 hours | Rosmarinic acid significantly inhibited NSCLC cell proliferation and cell colony formation in a dose-dependent manner, induced G1 phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to DDP. | Phytother Res. 2020 May;34(5):1142-1153 |
THP-1 macrophages | 1, 10, 50, 100 µM | 6 hours | To evaluate the effect of RA on cholesterol efflux. RA significantly increased ApoA1- and HDL-mediated cholesterol efflux in THP-1 macrophages. | Int J Mol Sci. 2021 Aug 16;22(16):8791 |
Vibrio parahaemolyticus | 1000 µM | 7 hours | Almost completely inhibited the growth of Vibrio parahaemolyticus | Int J Mol Sci. 2021 Dec 1;22(23):13010 |
Vibrio vulnificus | 1000 µM | 7 hours | Almost completely inhibited the growth of Vibrio vulnificus | Int J Mol Sci. 2021 Dec 1;22(23):13010 |
Vibrio metschnikovii | 1000 µM | 7 hours | Inhibited the growth of Vibrio metschnikovii, reducing the OD600 value to about one-quarter of the control group | Int J Mol Sci. 2021 Dec 1;22(23):13010 |
HT29 cells | 6.25-200 µM | Overnight | To evaluate the effect of rosmarinic acid on the viability of HT29 cells, results showed no significant effect on cell viability within the tested concentration range. | Neoplasia. 2021 Jun;23(6):561-573 |
HCT116 cells | 6.25-200 µM | Overnight | To evaluate the effect of rosmarinic acid on the viability of HCT116 cells, results showed no significant effect on cell viability within the tested concentration range. | Neoplasia. 2021 Jun;23(6):561-573 |
In Vivo:
Administration | Dosage | Frequency | Description | References |
NC/Nga mice | DfE-induced atopic dermatitis-like skin inflammation model | Oral | 1 or 3 mg/kg | Once daily for 14 days | To evaluate the effect of rosmarinic acid on DfE-induced atopic dermatitis-like skin inflammation. Results showed that rosmarinic acid significantly alleviated skin inflammation symptoms, reduced serum inflammatory marker levels, and decreased mast cell infiltration. | Int J Mol Sci. 2024 Nov 27;25(23):12737 |
Nude mice | NSCLC xenograft model | Intraperitoneal injection | 10 mg/kg | Daily, throughout the treatment | Rosmarinic acid combined with DDP significantly inhibited the growth of NSCLC xenograft tumors without affecting the health of nude mice. | Phytother Res. 2020 May;34(5):1142-1153 |
C57BL/6 mice | MC38 tumor xenograft mouse model | Oral | 100 mg/kg/day | Once daily for 4 weeks | Significantly reduced the number of metastatic foci in the lungs | Acta Pharmacol Sin. 2024 Jan;45(1):193-208. |
C57/B6 male mice | DOX-induced cardiotoxicity model | Oral | 100mg/kg/day | Consecutive 7 days | To evaluate the protective effect of rosmarinic acid on DOX-induced cardiotoxicity, results showed that RA significantly alleviated DOX-induced cardiomyocyte apoptosis and cardiac dysfunction. | Int J Biol Sci. 2019 Jan 1;15(3):556-567 |
Sprague-Dawley rats | Perinatal hypoxia/ischemia injury model | Intraperitoneal injection | 20 mg/kg | 5 consecutive days | Rosmarinic acid ameliorated motor, anxiety, learning and spatial memory impairments induced by hypoxia/ischemia injury, and promoted the proliferation of oligodendrocyte progenitor cells and remyelination | Neural Regen Res. 2020 May;15(5):894-902 |
Balb/c mice | AOM/DSS-induced colitis-associated colon cancer model | Oral | 30 mg/kg/day | Daily administration for one week | To evaluate the anti-tumor effects of rosmarinic acid in the AOM/DSS-induced colitis-associated colon cancer model, results showed that RA significantly reduced colitis severity, inflammation-related protein expression, tumor incidence, and colorectal adenoma development. | Neoplasia. 2021 Jun;23(6):561-573 |
Swiss albino mice | CdCl2-induced nephrotoxicity model | Oral | 50 mg/kg | Once daily for 14 days | Rosmarinic acid significantly attenuated CdCl2-induced nephrotoxicity, improved renal function parameters, and reduced oxidative stress and inflammation. | Int J Mol Sci. 2019 Apr 24;20(8):2027 |
C57Bl/6N mice | Mouse model of physiological aging | Oral administration | 500 mg/kg | 52 days | Rosmarinic acid improved cognitive abilities and glucose metabolism in aged mice while disrupting lipid profile in young adults in a sex-dependent fashion. | Nutrients. 2023 Jul 28;15(15):3366 |
C57BL/6 mice | High-fat diet-induced hyperlipidemia model | Oral gavage | 50 and 100 mg/kg/day | Once daily for 8 weeks | Rosmarinic acid treatment significantly decreased body weight, blood glucose, and plasma total cholesterol and triglyceride levels in HFD-fed mice. Rosmarinic acid increased the expression levels of cholesterol uptake-associated receptors in liver tissues, including scavenger receptor B type 1 (SR-B1) and low-density lipoprotein receptor (LDL-R). Furthermore, rosmarinic acid treatment notably increased the expression of cholesterol excretion molecules, ATP-binding cassette G5 (ABCG5) and G8 (ABCG8) transporters, and cholesterol 7 alpha-hydroxylase A1 (CYP7A1) as well as markedly reduced cholesterol and triglyceride levels in liver tissues. In addition, rosmarinic acid facilitated fatty acid oxidation through AMP-activated protein kinase (AMPK)-mediated carnitine palmitoyltransferase 1A (CPT1A) induction. | Biomolecules. 2021 Oct 6;11(10):1470 |
BALB/c mice | HSV-1 infection model | Intragastric administration | 11.7 or 23.4 mg/kg/d | Once daily for 23 days | RA significantly decreased stress-augmented mortality and alleviated eye swelling and neurological symptoms in HSV-1-infected mice | Acta Pharmacol Sin. 2023 Sep;44(9):1856-1866 |
Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
2.78mL 0.56mL 0.28mL |
13.88mL 2.78mL 1.39mL |
27.75mL 5.55mL 2.78mL |
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Dissolving Methods |
in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day; The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound. Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:
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