Description: |
Lariciresinol is an enterolignan precursor, it possesses fungicidal activities by disrupting the fungal plasma membrane and therapeutic potential as a novel antifungal agent for the treatment of fungal infectious diseases in humans. Dietary lariciresinol can attenuate mammary tumor growth and reduce blood vessel density in human MCF-7 breast cancer xenografts and carcinogen-induced mammary tumors in rats. |
Targets: |
VEGFR | Antifection |
In vitro: |
Biochem Biophys Res Commun. 2011 Jul 8;410(3):489-93. | Antifungal activity of lariciresinol derived from Sambucus williamsii and their membrane-active mechanisms in Candida albicans.[Pubmed: 21679690] | Lariciresinol is an enterolignan precursor isolated from the herb Sambucus williamsii, a folk medicinal plant used for its therapeutic properties. METHODS AND RESULTS: In this study, the antifungal properties and mode of action of Lariciresinol were investigated. Lariciresinol displays potent antifungal properties against several human pathogenic fungal strains without hemolytic effects on human erythrocytes. To understand the antifungal mechanism of action of Lariciresinol, the membrane interactions of Lariciresinol were examined. Fluorescence analysis using the membrane probe 3,3'-diethylthio-dicarbocyanine iodide (DiSC(3)-5) and 1,6-diphenyl-1,3,5-hexatriene (DPH), as well as a flow cytometric analysis with propidium iodide (PI), a membrane-impermeable dye, indicated that Lariciresinol was associated with lipid bilayers and induced membrane permeabilization.
CONCLUSIONS:
Therefore, the present study suggests that Lariciresinol possesses fungicidal activities by disrupting the fungal plasma membrane and therapeutic potential as a novel antifungal agent for the treatment of fungal infectious diseases in humans. |
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In vivo: |
Int J Cancer. 2008 Sep 1;123(5):1196-204. | Dietary lariciresinol attenuates mammary tumor growth and reduces blood vessel density in human MCF-7 breast cancer xenografts and carcinogen-induced mammary tumors in rats.[Pubmed: 18528864 ] | Lariciresinol is a dietary lignan that accounts for a significant portion of the total phytoestrogen intake from Western foods. Recent epidemiological studies suggest that high dietary intake of lignans and Lariciresinol is associated with reduced breast cancer risk. However, no causal relationship between Lariciresinol intake and breast cancer development has been established. METHODS AND RESULTS: In this study, we investigated for the first time the effects and possible mechanisms of action of Lariciresinol on hormone responsive mammary cancer in vivo in dimethylbenz[a]anthracene induced mammary cancer in rats, and in human MCF-7 breast cancer xenografts in athymic mice. For tumor bearing rats, Lariciresinol (3 or 15 mg/kg of body weight) or vehicle was administered p.o. daily for 9 weeks. For E2-maintained ovariectomized athymic mice bearing orthotopic MCF-7 tumors, control diet (AIN-93G) or Lariciresinol containing diet (AIN-93G supplemented with 20 or 100 mg of Lariciresinol/kg of diet) was administered for 5 weeks. In both models, Lariciresinol administration inhibited the tumor growth and tumor angiogenesis. In MCF-7 cells, enterolactone significantly inhibited the E2-stimulated VEGF secretion. Moreover, in MCF-7 xenografts, Lariciresinol administration enhanced tumor cell apoptosis and increased estrogen receptor beta expression. Lariciresinol and its further metabolites secoisoLariciresinol, enterodiol and enterolactone were found in serum of both rats and athymic mice confirming a similar lignan metabolism pattern as in humans.
CONCLUSIONS:
These findings indicate conceivable importance of dietary lignan Lariciresinol in inhibition of breast cancer development. |
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