PMID: 

Biosci Biotechnol Biochem. 2003 Feb ;67(2):445-7. PMID: 12729019

Abstract Title: 

6-hydroxyflavonoids as alpha-glucosidase inhibitors from marjoram (Origanum majorana) leaves.

Abstract: 

A methanol extract of marjoram leaves strongly inhibited rat intestinal alpha-glucosidase. Five 6-hydroxyflavonoids, 6-hydroxyapigenin (scutellarein; IC50 for sucrose hydrolysis by rat intestinal alpha-glucosidase, 12 microM), 6-hydroxyapigenin-7-O-beta-D-glucopyranoside (>500 microM), 6-hydroxyluteolin-7-O-beta-D-glucopyranoside (300 microM), 6-hydroxyapigenin-7-O-(6-O-feruloyl)-beta-D-glucopyranoside (>500 microM), and 6-hydroxyluteolin-7-O-(6-O-feruloyl)-beta-D-glucopyranoside (>500 microM), were isolated as active principles and related compounds. The two feruloylglucosides are novel compounds.

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PMID: 

Leuk Res. 2010 Aug ;34(8):1052-6. Epub 2009 Oct 23. PMID: 19853912

Abstract Title: 

The apoptotic and anti-proliferative activity of Origanum majorana extracts on human leukemic cell line.

Abstract: 

Scientists are constantly searching for phytochemicals and compounds with anti-cancer and antioxidant activity. In this study, the anti-proliferative activity of plant extracts from Origanum majorana (marjoram) was tested on human lymphoblastic leukemia cell line Jurkat. Cytotoxicity was examined using non-radioactive cytotoxicity assay and the IC(50) was calculated. At non-cytotoxic concentrations, the viability of cells decreased with increase of concentration of plant extract. The anti-proliferative effect was also found to be dose-dependent. Analysis via flow cytometry shows that marjoram extracts stimulated apoptosis. Induction of apoptosis was caused by an up-regulation of p53 protein levels and down-regulation of Bcl-2alpha. Marjoram exhibited a strong scavenging activity (SC(50)=0.03mg dry weight). The conclusions from this study suggest that marjoram extracts exhibit anti-proliferative effect and high antioxidant activity. For that it merits further investigation as a potential therapeutic agent.

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PMID: 

Cardiovasc Toxicol. 2013 Jun ;13(2):100-9. PMID: 23054890

Abstract Title: 

Preventive effects of Egyptian sweet marjoram (Origanum majorana L.) leaves on haematological changes and cardiotoxicity in isoproterenol-treated albino rats.

Abstract: 

We made an attempt to evaluate/compare the cardioprotective activity of two different doses (50 and 100 mg/kg body weight, given orally for 30 consecutive days) of Egyptian sweet marjoram leaf powder (MLP) and marjoram leaf aqueous extract (MLE) against isoproterenol (ISO)-induced myocardial infarcted rats (150 mg/kg body weight, twice at an interval of 24 h on days 29 and 30). The present study showed (probably for the first time) that both MLP and MLE (especially the high dose) significantly alleviated (P

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PMID: 

PLoS One. 2013 ;8(2):e56649. Epub 2013 Feb 22. PMID: 23451065

Abstract Title: 

Mitotic arrest and apoptosis in breast cancer cells induced by Origanum majorana extract: upregulation of TNF-α and downregulation of survivin and mutant p53.

Abstract: 

BACKGROUND: In the present study, we investigated the effect of Origanum majorana ethanolic extract on the survival of the highly proliferative and invasive triple-negative p53 mutant breast cancer cell line MDA-MB-231.
RESULTS: We found that O. majorana extract (OME) was able to inhibit the viability of the MDA-MB-231 cells in a time- and concentration-dependent manner. The effect of OME on cellular viability was further confirmed by the inhibition of colony growth. We showed, depending on the concentration used, that OME elicited different effects on the MDA-MB 231 cells. Concentrations of 150 and 300µg/mL induced an accumulation of apoptotic-resistant population of cells arrested in mitotis and overexpressing the cyclin-dependent kinase inhibitor, p21 and the inhibitor of apoptosis, survivin. On the other hand, higher concentrations of OME (450 and 600 µg/mL) triggered a massive apoptosis through the extrinsic pathway, including the activation of tumor necrosis factor-α (TNF-α), caspase 8, caspase 3, and cleavage of PARP, downregulation of survivin as well as depletion of the mutant p53 in MDA-MB-231 cells. Furthermore, OME induced an upregulation of γ-H2AX, a marker of double strandDNA breaks and an overall histone H3 and H4 hyperacetylation.
CONCLUSION: Our findings provide strong evidence that O. majorana may be a promising chemopreventive and therapeutic candidate against cancer especially for highly invasive triple negative p53 mutant breast cancer; thus validating its complementary and alternative medicinal use.

PMID: 

PLoS One. 2013 ;8(7):e68808. Epub 2013 Jul 10. PMID: 23874773

Abstract Title: 

Anti-metastatic and anti-tumor growth effects of Origanum majorana on highly metastatic human breast cancer cells: inhibition of NFκB signaling and reduction of nitric oxide production.

Abstract: 

BACKGROUND: We have recently reported that Origanummajorana exhibits anticancer activity by promoting cell cycle arrest and apoptosis of the metastatic MDA-MB-231 breast cancer cell line. Here, we extended our study by investigating the effect of O. majorana on the migration, invasion and tumor growth of these cells.RESULTS: We demonstrate that non-cytotoxic concentrations of O. majorana significantly inhibited the migration and invasion of the MDA-MB-231 cells as shown by wound-healing and matrigel invasion assays. We also show that O. majorana induce homotypic aggregation of MDA-MB-231 associated with an upregulation of E-cadherin protein and promoter activity. Furthermore, we show that O. majorana decrease the adhesion of MDA-MB-231 to HUVECs and inhibits transendothelial migration of MDA-MB-231 through TNF-α-activated HUVECs. Gelatin zymography assay shows that O. majorana suppresses the activities of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9). ELISA, RT-PCR and Western blot results revealed that O. majorana decreases the expression of MMP-2, MMP-9, urokinase plasminogen activator receptor (uPAR), ICAM-1 and VEGF. Further investigation revealed that O. majorana suppresses the phosphorylation of IκB, downregulates the nuclear level of NFκB and reduces Nitric Oxide (NO) production in MDA-MB-231 cells. Most importantly, by using chick embryo tumor growth assay, we also show that O. majorana promotes inhibition of tumor growth and metastasis in vivo.CONCLUSION: Our findings identify Origanummajorana as a promising chemopreventive and therapeutic candidate that modulate breast cancer growth and metastasis.

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PMID: 

Nutrients. 2016 May 5 ;8(5). Epub 2016 May 5. PMID: 27164131

Abstract Title: 

Origanum majorana Attenuates Nephrotoxicity of Cisplatin Anticancer Drug through Ameliorating Oxidative Stress.

Abstract: 

Despite the fact that cisplatin is an important anticancer drug, its clinical utilization is limited by nephrotoxicity during long term medication. Combined cisplatin chemotherapy with plant extracts can diminish toxicity and enhance the antitumor efficacy of the drug. This study evaluated the effect of Originum majorana ethanolic extract (OMEE) on cisplatin-induced nephrotoxicity. Eighteen male rats were divided into three groups as follows: a control group, a group treated with cisplatin (3 mg/kg body weight), and a group that received both cisplatin and OMEE (500 mg/kg body weight) for 14 days. Cisplatin induced a significant increase in creatinine, urea, uric acid, blood urea nitrogen, malondialdehyde, and nitric oxide levels. However, glutathione, superoxide dismutase, and catalase levels were significantly diminished. Conversely, OMEE significantly modulated the renal and oxidative markers negatively impacted by cisplatin. OMEE significantly reduced the effects of cisplatin-induced changes in renal and oxidative markers, possibly through its free radical scavenging activity. Thus, OMEE may be combined with cisplatin to alleviate nephrotoxicity in cancer chemotherapy.

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PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:2421695. Epub 2019 Jan 15. PMID: 30766611

Abstract Title: 

,, andEssential Oils: Chemical Composition, Antimicrobial and Antileishmanial Activity.

Abstract: 

The resistance mechanisms of bacteria and protozoans have evidenced the need of discover new compounds with potential pharmaceutical activity against pathogenic microorganisms. Medicinal plants have been for centuries a promising alternative as sources of new drugs. The objective of this work was to evaluate the chemical composition, antimicrobial and antileishmanial activities of,, andessential oils. Chemical analysis was performed by gas chromatography-mass spectrometry. Antimicrobial activity was performed by disk diffusion and minimum inhibitory concentration (MIC) test. Antileishmanial activity was performed against antipromastigote and intracellular amastigote of. Cytotoxic and nitrite production were realized in BALB/c peritoneal macrophages. The major compounds of the essential oils were cinnamic aldehyde (46.30%) in, cis-p-menth-2-en-1-ol (33.88%) and linalyl acetate (13.90%) in, and turmerone (55.43%) in. The MIC showed significant antimicrobial activity ofessential oil against(83.3± 14.43g/mL). Antipromastigote activity showed ICvalues>500g/mL to, 308.4± 1.402g/mL to, and 405.5± 1.119g/mL toessential oil. Activity against intracellular amastigote ofshowed ICof 63.3± 1.369g/mL and cytotoxic was not observed, resulting in selectivity index higher than 15.79 to parasite.essential oil decreased nitrite production in peritoneal macrophages, but not ininfected cells. The chemical composition of the three essential oils is directly associated to its potential biological action, as the antimicrobial activity.presented a potent antileishmanial activity against promastigote and intracellular amastigote of, although this activity is not linked to nitric oxide, sinceessential oil inhibits its production.

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PMID: 

Front Oncol. 2019 ;9:795. Epub 2019 Aug 21. PMID: 31497536

Abstract Title: 

Ethanolic Extract Promotes Colorectal Cancer Cell Death by Triggering Abortive Autophagy and Activation of the Extrinsic Apoptotic Pathway.

Abstract: 

Colorectal cancer is considered as the third leading cause of cancer death. In the present study, we investigated the potential anticancer effect and the molecular mechanism ofethanolic extract (OME) against human colorectal cancer cells. We showed that OME exhibited strong anti-proliferative activity in a concentration- and time-dependent manner against two human colorectal cancer cell lines (HT-29 and Caco-2). OME inhibited cell viability, colony growth and induced mitotic arrest of HT-29 cells. Also, OME induced DNA damage, triggered abortive autophagy and activated a caspase 3 and 7-dependent extrinsic apoptotic pathway, most likely through activation of the TNFα pathway. Time-course analysis revealed that DNA damage occurred concomitantly with abortive autophagy after 4 h post-OME treatment while apoptosis was activated only 24 h later. Blockade of autophagy initiation, by 3-methyladenine, partially rescued OME-induced cell death. Cell viability arose from 37% in control group to 67% in group pre-treated with 3-MA before addition of OME. Inhibition of apoptosis, however, had a minimal effect on cell viability; it rose from 37% in control group to 43% in group pre-treated with Z-VAD-FMK. We also found that OME downregulated survivin in HT-29 cells.Our findings provide a strong evidence thatextract possesses strong anti-colon cancer potential, at least, through induction of autophagy and apoptosis. These finding provide the basis for therapeutic potential ofin the treatment of colon cancer.

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PMID: 

J Ethnopharmacol. 2019 Aug 27 ;246:112188. Epub 2019 Aug 27. PMID: 31470085

Abstract Title: 

Antifungal and biofilm inhibitory effect of Cymbopogon citratus (lemongrass) essential oil on biofilm forming by Candida tropicalis isolates; an in vitro study.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (lemongrass) essential oil has been widely used as a traditional medicine and is well known for antimicrobial properties. Therefore, it might be a potent anti-infective and biofilm inhibitive against Candida tropicalis infections. Until now, no ideal coating or cleaning method based on an essential oil has been described to prevent biofilm formation of Candida strains on silicone rubber maxillofacial prostheses, voice prostheses and medical devices susceptible to C. tropicalis infections.AIM OF THE STUDY: To investigate the antifungal and biofilm inhibitory effects of Cymbopogon citratus oil. Clinical isolates of C. tropicalis biofilms on different biomaterials were used to study the inhibitory effect.MATERIALS AND METHODS: The efficacy of Cymbopogon citratus, Cuminum cyminum, Citrus limon and Cinnamomum verum essential oils were compared on biofilm formation of three C. tropicalis isolates on 24 well polystyrene plates. C. citratus oil coated silicone rubber surfaces were prepared using hypromellose ointment as a vehicle. The antifungal tests to determine minimum inhibitory and minimum fungicidal concentrations were assessed by a microbroth dilution method and biofilm formation was determined by a crystal violet binding assay.RESULTS: C. tropicalis strains formed more biofilm on hydrophobic materials than on hydrophilic glass. C. citratus oil showed a high antifungal effect against all C. tropicalis strains. For comparison, C. limon oil and C. cyminum oil showed minor to no killing effect against the C. tropicalis strains. C. citratus oil had the lowest minimal inhibitory concentration of all essential oils tested and inhibited biofilm formation of all C. tropicalis strains. C. citratus oil coating on silicone rubber resulted in a 45-76% reduction in biofilm formation of all C. tropicalis strains.CONCLUSION: Cymbopogon citratus oil has good potential to be used as an antifungal and antibiofilm agent on silicone rubber prostheses and medical devices on which C. tropicalis biofilms pose a serious risk for skin infections and may cause a shorter lifespan of the prosthesis.

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PMID: 

Environ Sci Pollut Res Int. 2019 Aug 29. Epub 2019 Aug 29. PMID: 31468354

Abstract Title: 

Efficacy of different citrus essential oils to inhibit the growth and B1 aflatoxin biosynthesis of Aspergillus flavus.

Abstract: 

Food contamination by aflatoxin B1 (AFB1), produced by mycotoxigenic strains of Aspergillus spp., causes severe medical and economic implications. Essential oils (EOs) are mixtures of eco-friendly natural volatile substances. Their ability to inhibit fungal growth has been investigated, while no data are available about their efficacy in inhibition of AFB1 biosynthesis. This study investigates the efficacy of five different citrus EOs to inhibit the growth and AFB1 synthesis of A. flavus through in vitro tests for a future application in food matrices. AFB1 detection was carried out by LC-ESI-TQD analytical approach. Lemon (Citrus limon (L.) Burm. f.), bergamot (Citrus bergamia Risso), and bitter orange (Citrus aurantium L.) EOs were the most effective causing a 97.88%, 97.04%, and 96.43% reduction in mycelial growth, respectively. Sweet orange and mandarin EOs showed the lowest percentage of mycelial growth reduction. Citrus EOs showed different capacity of AFB1 inhibition (lemon>bitter orange>bergamot>sweet orange>mandarin). Our results showed a dose-dependent antifungal activity of lemon, bitter orange, and bergamot EOs which at 2% (v/v) inhibited both mycelium growth and AFB1 genesis of A. flavus. Our results show that EOs' use can be a pivotal key to recovery and reuse of citrus fruit wastes and to be used as eco-friendly fungicides for improvement of food safety. The use of EOs obtained at low cost from the residues of citric industry presents an interesting option for improving the profitability of the agriculture.

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