Oleocanthal

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Oleocanthal
Oleocanthal
Names
IUPAC name
2-(4-hydroxyphenyl)ethyl (3S,4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate
Identifiers
  • 289030-99-5 ☑Y
3D model (JSmol)
  • Interactive image
ChEBI
  • CHEBI:85673 ☒N
ChemSpider
  • 9827154 ☑Y
  • 6308
Properties
C17H20O5
Molar mass 304.34 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is ☑Y☒N ?)
Infobox references

Oleocanthal is a phenylethanoid, or a type of natural phenolic compound found in extra-virgin olive oil. It appears to be responsible for the burning sensation that occurs in the back of the throat when consuming such oil. Oleocanthal is a tyrosol ester and its chemical structure is related to oleuropein, also found in olive oil.

Potential biological effects

Anti-inflammatory

Oleocanthal has been found to have anti-inflammatory and antioxidant properties in vitro. Similar to classical non-steroidal anti-inflammatory drugs, it is a non-selective inhibitor of cyclooxygenase (COX). 50 g (more than three and a half tablespoons) of a typical extra virgin olive oil per day contains an amount of oleocanthal with similar in vitro anti-inflammatory effect as 1/10 of the adult ibuprofen dose.[1] It is therefore suggested that long-term consumption of small quantities may be responsible in part for the low incidence of heart disease and Alzheimer's disease associated with a Mediterranean diet.[2][3] However, 50 g is a great deal of olive oil for most consumers; moreover, the absorption, metabolism, and distribution of oleocanthal is not well characterized, and it is not known whether these in vitro effects actually occur in the body.[4] "Against this background, the in vivo anti-inflammatory effects of dietary oleocanthal cannot be as relevant as hypothesized by Beauchamp et al."[4]

Oleocanthal is an activator of the TRPA1 ion channel, which is activated by ibuprofen. Oleocanthal is found to be responsible for the burning sensation when consuming extra-virgin olive oil.[5][6]

Recently it has been demonstrated that oleocanthal shows potential as a therapeutic agent in the treatment of inflammatory degenerative joint diseases.[7] Oleocanthal inhibits LPS-induced NO production in J774 macrophages, without affecting cell viability. Moreover, it inhibits MIP-1α and IL-6 mRNA expression, as well as protein synthesis, in both ATDC5 chondrocytes and J774 macrophages. Oleocanthal also inhibits IL-1β, TNF-α and GM-CSF protein synthesis from LPS-stimulated macrophages.[8]

Beta-amyloid

Studies in an animal model suggest that oleocanthal can reduce the accumulation of β-amyloid proteins via up-regulation of P-glycoprotein and LRP1.[3]

Selective cytotoxicity

Oleocanthal is capable of killing a variety of human cancer cells in vitro while leaving healthy cells unharmed.[9] While apoptosis requires between 16 and 24 hours, oleocanthal operated within 30 minutes to one hour. Oleocanthal pierces cancer cells' lysosomes, the containers that store the cell's waste products, releasing enzymes that kill the cell. In healthy cells, the application of oleocanthal caused a temporary halt in their life cycles, but after 24 hours they returned to normal.[10]

Oleocanthal inhibits the enzymatic activity of mammalian target of rapamycin (mTOR) with an IC50 value of 708 nM.[11] Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose-dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA-MB-231). These results strongly indicate that mTOR inhibition is at least one of the factors of the reported anticancer and neuroprotective properties of oleocanthal.[11]

Cell apoptosis is tested by treating the lysosomal membrane with acridine orange. Acridine orange radiates a red fluorescent color at an increased concentration in a lysosome that is undamaged. Oleocanthal weakens the red fluorescent color indicating apoptosis; however, non-cancerous cells will not experience apoptosis. This is a result of lysosome membrane permeabilization promoting cancer cell death. Lysosomal membrane permeabilization is not activated by oleocanthal in non-cancerous cells.[12]

Oleocanthal has also been shown in vitro to inhibit c-met, an important tyrosine kinase receptor which is responsible for proliferation of many cell types. The same study that found these results also showed that oleocanthal had no deleterious effects on healthy control cells over a span of 48 hours, the same amount of time that it took for inhibition of c-met in MB-231 breast cancer cells. Cells are forced into cell cycle arrest during G1 phase, effectively decreasing the viability of this highly invasive cell line.[13]

Potential Medical Uses

Although it is not being administered as a drug currently, many strategies are being studied to use oleocanthal as a small drug inhibitor of c-met, as well a potential monoclonal antibody against HGF and c-Met.

See also

References

  1. ^ "Extra-virgin olive oil mimics painkiller". Nature Publishing Group. 31 August 2005.
  2. ^ Beauchamp GK, Keast RS, Morel D, et al. (September 2005). "Phytochemistry: ibuprofen-like activity in extra-virgin olive oil". Nature. 437 (7055): 45–6. doi:10.1038/437045a. PMID 16136122.
  3. ^ a b Abuznait, AH; Qosa, H; Busnena, BA; El Sayed, KA; Kaddoumi, A (Feb 25, 2013). "Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer's Disease: In Vitro and in Vivo Studies". ACS Chemical Neuroscience. 4 (6): 973–82. doi:10.1021/cn400024q. PMC 3689195. PMID 23414128.
  4. ^ a b Fogliano, Vincenzo; Raffaele Sacchi (January 2006). "Oleocanthal in olive oil: Between myth and reality". Molecular Nutrition & Food Research. 50 (1): 5–6. doi:10.1002/mnfr.200690002. PMID 16397870.
  5. ^ Catherine Peyrot des Gachons; Kunitoshi Uchida; Bruce Bryant; Asako Shima; Jeffrey B. Sperry; Luba Dankulich-Nagrudny; Makoto Tominaga; Amos B. Smith III; Gary K. Beauchamp; Paul A. S. Breslin (January 2011). "Unusual pungency from extra-virgin olive oil is attributable to restricted spatial expression of the receptor of oleocanthal". J. Neurosci. 31 (3): 999–1009. doi:10.1523/JNEUROSCI.1374-10.2011. PMC 3073417. PMID 21248124.
  6. ^ Cicerale, Sara; Paul A.S. Breslin; Gary K. Beauchamp; Russell S.J. Keast (May 2009). "Sensory characterization of the irritant properties of oleocanthal, a natural anti-inflammatory agent in extra virgin olive oils". Chem Senses. 34 (4): 333–9. doi:10.1093/chemse/bjp006. PMC 4357805. PMID 19273462.
  7. ^ Iacono, A; Gómez, R; Sperry, J; Conde, J; Bianco, G; Meli, R; Gómez-Reino, JJ; Smith Ab, 3rd; Gualillo, O (2010). "Effect of oleocanthal and its derivatives on inflammatory response induced by lipopolysaccharide in a murine chondrocyte cell line". Arthritis and Rheumatism. 62 (6): 1675–82. doi:10.1002/art.27437. PMID 20201078.
  8. ^ Scotece, Morena; Gómez, Rodolfo; Conde, Javier; Lopez, Verónica; Gómez-Reino, Juan J.; Lago, Francisca; Smith, Amos B.; Gualillo, Oreste (2012). "Further evidence for the anti-inflammatory activity of oleocanthal: Inhibition of MIP-1α and IL-6 in J774 macrophages and in ATDC5 chondrocytes". Life Sciences. 91 (23–24): 1229–35. doi:10.1016/j.lfs.2012.09.012. PMID 23044226.
  9. ^ Mihai, Andrei (February 20, 2015). "Olive Oil Compound Kills Cancer Cells Within an Hour". ZME Science. Retrieved February 22, 2015.
  10. ^ Lavars, Nick (February 19, 2015). "Olive oil ingredient leads cancer cells to their death". Retrieved February 2015. Check date values in: |access-date= (help)
  11. ^ a b Khanfar, Mohammad A.; Bardaweel, Sanaa K.; Akl, Mohamed R.; El Sayed, Khalid A. (2015-01-01). "Olive Oil-derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies". Phytotherapy Research. 29: 1776–1782. doi:10.1002/ptr.5434. ISSN 1099-1573. PMC 5051273.
  12. ^ Foster, David; LeGendre, Onica; Breslin, Paul (September 2015). "(-)-Oleocanthal rapidly and selectively induces cancer cell death via lysosomal membrane permeabilization". Molecular & Cellular Oncology. 2 (4): 1–17. doi:10.1080/23723556.2015.1006077. PMC 4568762. Retrieved 3 May 2018.
  13. ^ Akl, Mohamed; Ayoub, Nehad; Mohyeldin, Mohamed (May 21, 2014). "Olive Phenolics as c-Met Inhibitors: (-)-Oleocanthal Attenuates Cell Proliferation, Invasiveness, and Tumor Growth in Breast Cancer Models". PLoS ONE. 9 (5): 1–15.

External links

  • Article about oleocanthal and extra virgin olive oil in Scientific American
  • Smith, Amos B., III; Han, Qiang; Breslin, Paul A. S.; Beauchamp, Gary K. (2005). "Synthesis and Assignment of Absolute Configuration of (−)-Oleocanthal: A Potent, Naturally Occurring Non-steroidal Anti-inflammatory and Anti-oxidant Agent Derived from Extra Virgin Olive Oils". Organic Letters. 7 (22): 5075–5078. doi:10.1021/ol052106a. PMID 16235961.
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