Scientific Info about Olive Leaf Extract

Computational study of bindings of olive leaf extract (OLE) to HIV-1 fusion protein gp41.

Bao J1, Zhang DW, Zhang JZ, Huang PL, Huang PL, Lee-Huang S.

 

Recent experimental study found that OLE (olive leaf extract) has anti-HIV activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L., Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang, P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872-878, 879-884]. As part of a joint experimental and theoretical effort, we report here computational study to help identify and characterize the binding complexes of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein gp41. A number of possible binding modes are found by docking oleuropein and its metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic pocket on gp41. Detailed OLE-gp41 binding interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in our predicted OLE/gp41 complexes are identified and hydroxytyrosol is identified to be the main moiety for binding to gp41. This computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of OLE-based gp41 inhibitors.

 

PubMeb.gov US National Library of Medicine National Institutes of Health

Studies on the Mechanism of the Antimicrobial Action of Oleuropein

Authors Juven, B., Henis, Y. and Jacoby, B

Oleuropein, the bitter principle of green olives, is surface active; this and its effect on cell membranes, as demonstrated with human erythrocytes, seems to be the basis of its antimicrobial activity. Oleuropein effected a significant leakage of glutamate, potassium and inorganic phosphate from Lactobacillus plantarum. Oleuropein had no effect on the rate of glycolysis when added to resting cells of L. plantarum but it caused a decrease in the ATP content of the cells.

Olive (Olea europaea L.) Leaf Polyphenols Improve Insulin Sensitivity in Middle-Aged Overweight Men: A Randomized, Placebo-Controlled, Crossover Trial

Martin de Bock,1 José G. B. Derraik,1 Christine M. Brennan,1 Janene B. Biggs,1 Philip E. Morgan,2 Steven C. Hodgkinson,1 Paul L. Hofman,1,3 and Wayne S. Cutfield1,3,*

 

Supplementation with olive leaf polyphenols for 12 weeks significantly improved insulin sensitivity and pancreatic β-cell secretory capacity in overweight middle-aged men at risk of developing the metabolic syndrome.

 

US National Library of Medicine National Institutes of Health

Antibacterial, antifungal, antibiotic, anti-inflammatory

Olive leaf products are now marketed as anti-aging, immunostimulator, and antibiotic agents. (1)

Clinical evidence supports oleuopeins antibacterial, antifungal, and anti-inflammatory effects at a laboratory level. A liquid extract made directly from fresh olive leaves gained international attention when it was shown to have an antioxidant capacity almost double green tea extract and 400% higher than vitamin C. (2)

References:

  • Kilham, Chris, Healing Power of Olive Leaf, [1]

  • Dr Stevenson, L,. et al. Oxygen Radical Absorbance Capacity (ORAC) Report on Olive Leaf Australia’s Olive Leaf Extracts, Southern Cross University, 2005. (2)

Scientist have isolated the molecule that provides products from the olive tree with life extending benefits, this molecule, a polyphenol, that can help lower bad cholesterol and blood pressure, prevent cancer and protect against oxidative damage and help guard against cognitive decline.  The olive leaf  has antioxidant, anti-inflammatory and disease fighting characteristics.

The primary active compounds in olive leaf are believed to be the antioxidants oleuropein and hydroxytyrosol, as well as several other polyphenols and flavonoids, including oleocanthal.   Elenolic acid is a component of olive oil and olive leaf.

Olive leaf harbours antioxidant properties that help protect the body from the continuous activity of free radicals. (3,6,9,10,11,12,13). Free radicals are highly reactive chemical substances that can cause cellular damage if left unchecked. Some recent research on the olive leaf has shown its antioxidants to be effective in treating some tumors and cancers such as liver, prostate, colon, skin and breast cancer, clinical studies lacking; Olive leaf is especially potent when used in combination with other antioxidants. (14,15,16)

References:

  • Somova et al. Antihypertensive, antiatherosclerotic and antioxidant activity of triterpenoids isolated from Olea europaea, subspecies africana leaves, 2003. (3)

  • Dr Stevenson, L,. et al. Oxygen Radical Absorbance Capacity (ORAC) Report on Olive Leaf Australia’s Olive Leaf Extracts, Southern Cross University, 2005. (6)

  • Khayyal et al. Blood pressure lowering effect of an olive leaf extract (Olea europaea) in L-NAME induced hypertension in rats, 2002 (6)

  • Benavente-Garcia et al. Antioxidant activity of phenols extracted from Olea europaea L. leaves, 2000. (9)

  • Saija et al. In vitro evaluation of the antioxidant activity and biomembrane interaction of the plant phenols oleuropein and hydroxytyrosol, 1998. (10)

  • Birante et al. Olea europaea L. leaf extract and derivatives: antioxidant properties, 2002. (11)

  • Speroni et al. Oleuropein Evaluated In Vitro and In Vivo as an Antioxidant, 1998. (12)

  • Pinelli et al. Quali-quantitative analysis and antioxidant activity of different polyphenolic extracts from Olea europea L. leaves, 2000. (13)

  • Hamdi et al. Oleuropein, a non-toxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor, 2005. (14)

  • Dr Stevenson, L,. et al. In vitro Biological Activities of Pure Olive Leaf Extract & High Strength Olive Leaf Extract, 2006. (15)

  • Muneer Abuismail. Analysis and Biological Evaluation of Jordanian Olive Trees Leaves – Cancer Cure Invention With Tissue Repair Potential, 2011. (16)

Blood pressure

Oleuropein is a bioactive compound found in the olive leaf.  When oleuropein  was tested on hypertension sufferers (high blood pressure) the blood pressure was reduced significantly and also provided other vascular benefits.  Olive tree fruit has numerous  beneficial compounds including  hydroxytyrosol, oleacein, ursolic,and oleanic acids.

However, it is oleuropein, found in the leaf of the olive tree, that is largely responsible for the beneficial effect on high blood pressure (5-9)

A multitude of factors underlies uncontrolled blood pressure. Many cases of hypertension involve increased arterial stiffness.(10)  This stiffness, or lack of elasticity, usually begins in the arterioles—tiny peripheral arteries most distant from the heart—and eventually spreads to larger arteries.

Oleuropein has been shown to specifically target arterial resistance and stiffness, improving endothelial function and bringing blood pressure under control. It accomplishes this in part by modulating calcium channel flow—with an excellent tolerability profile. (4,11-14)

While tolerability has been excellent with oleuropein, the list of side effects associated with other blood pressure medications is long. This list includes swollen ankles and feet (edema),(15) gastrointestinal bleeding,(16) kidney impairment,(17,18) excess potassium in the blood, (19,20) negative interactions with other drugs,(18) and, paradoxically, increased risk of heart attack. (21)

Arterial Health

Blood pressure is only one measure of cardiovascular health; arterial health is equally important. The endothelial cells that line arterial walls play a key role in maintaining blood flow and pressure; they also regulate the distribution of smooth muscle cells and sustain an even flow of blood through vessels. Endothelial dysfunction is one of the earliest stages in hardening of the arteries (atherosclerosis), which occurs when plaques build up in the arterial walls. These plaques eventually block blood flow and can trigger a heart attack or stroke.

Olive leaf fights endothelial dysfunction at multiple levels. They increase the production of nitric oxide, a signaling molecule that helps relax blood vessels. (16,17).  They reduce the production and activity of a class of molecules known as matrix metalloproteinases, or MMPs.(18-20).  Excessive MMP activity literally dissolves the gel-like matrix that holds cells together, making vessel linings increasingly vulnerable to plaque damage. They also help prevent the oxidation of LDL-cholesterol, which is one of the earliest events in developing atherosclerosis. (21-23)  Oxidized LDL triggers inflammation, further damaging arteries, and olive leaf extract has multi-targeted anti-inflammatory effects (20,24,25)

Polyphenol compounds found in olive leaves have been shown to help directly prevent the formation of arterial plaques (and thereby reduce the risk of heart attack and stroke) in two ways. First, they reduce the production and activity of a series of “adhesion molecules.(26-28)  These substances cause white blood cells and platelets to stick to arterial walls, resulting in early plaque formation. Second, they reduce platelet aggregation (clumping) by multiple mechanisms, which reduces the risk that tiny clots will form at sites of plaque to produce a stroke or heart attack. (29,30)

References:

  • Susalit E, Agus N, Effendi I, et al. Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with captopril. Phytomedicine. 2011 Feb 15;18(4):251-8. (4)

  • Jänicke C, Grünwald J, Brendler T. Handbuch Phytotherapie. Stuttgart, Germany: Wissenschaftliche Verlagsgesellschaft; 2003. (5)

  • Cherif S, Rahal N, Haouala M, et al. A clinical trial of a titrated Olea extract in the treatment of essential arterial hypertension. J Pharm Belg. 1996 Mar-Apr;51(2):69-71. (6)

  • Bennani-Kabchi N, Fdhil H, Cherrah Y, et al. Effects of Olea europaea var. oleaster leaves in hypercholesterolemic insulin-resistant sand rats. Therapie. 1999 Nov-Dec;54(6):717-23. (7)

  • Bennani-Kabchi N, Fdhil H, Cherrah Y, El Bouayadi F, Kehel L, Marquie G. Therapeutic effect of Olea europea var. oleaster leaves on carbohydrate and lipid metabolism in obese and prediabetic sand rats (Psammomys obesus). Ann Pharm Fr. 2000 Jul;58(4):271-7. (8)

  • Petkov V, Manolov P. Pharmacological analysis of the iridoid oleuropein. Arzneiforschung. 1972 Sep;22(9):1476-86. (9)

  • Perrinjaquet-Moccetti1 T, Busjahn A, Schmidlin C, Schmidt A, Brad B, Aydogan C. Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins. Phytother. Res.2008;22:1239-42. (11)

  • Gilani AH, Khan A, Shah AJ, Connor J, Jabeen Q. Blood pressure lowering effect of olive is mediated through calcium channel blockade. Int J Food Sci Nutr. 2005 Dec;56(8):613-20. (14)

  • Pedrinelli R, Dell’Omo G, Mariani M. Calcium channel blockers, postural vasoconstriction and dependent oedema in essential hypertension. J Hum Hypertens. 2001 Jul;15(7):455. (15)

  • Pahor M, Guralnik JM, Furberg CD, Carbonin P, Havlik R. Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old. Lancet. 1996 Apr 20;347(9008):1061. (16)

  • Textor SC. Renal failure related to angiotensin-converting enzyme inhibitors. Semin Nephrol. 1997 Jan;17(1):67-76. (17)

  • Thomas MC. Diuretics, ACE inhibitors and NSAIDs–the triple whammy. Medical J Aust. 2000 Feb 21;172(4):184-5. (18)

  • Textor SC, Bravo EL, Fouad FM, et al. Hyperkalemia in azotemic patients during angiotensin-converting enzyme inhibition and aldosterone reduction with captopril. Am J Med. 1982 Nov;73(5):719-25. (19)

  • Cruz CS, Cruz AA, Marcilio de Souza CA. Hyperkalaemia in congestive heart failure patients using ACE inhibitors and spironolactone. Nephrol Dial Transplant. 2003 Sep;18(9):1814-9. (20)

  • Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA. 1995 Aug 23-30;274(8):620-5. (21)

  • Masella R, Vari R, D’Archivio M, et al. Extra virgin olive oil biophenols inhibit cell-mediated oxidation of LDL by increasing the mRNA transcription of glutathione-related enzymes. J Nutr.2004 Apr;134(4):785-91. (23)

  • Wang L, Geng C, Jiang L, et al. The anti-atherosclerotic effect of olive leaf extract is related to suppressed inflammatory response in rabbits with experimental atherosclerosis. Eur J Nutr. 2008 Aug;47(5):235-43. (24)

  • Impellizzeri D, Esposito E, Mazzon E, et al. The effects of oleuropein aglycone, an olive oil compound, in a mouse model of carrageenan-induced pleurisy. Clin Nutr. 2011 Aug;30(4):533-40. (25)

  • Carluccio MA, Siculella L, Ancora MA, et al. Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscler Thromb Vasc Biol. 2003 Apr 1;23(4):622-9. (26)

  • Dell’Agli M, Fagnani R, Mitro N, et al. Minor components of olive oil modulate proatherogenic adhesion molecules involved in endothelial activation. J Agric Food Chem. 2006 May 3;54(9):3259-64. (28)

  • Singh I, Mok M, Christensen AM, Turner AH, Hawley JA. The effects of polyphenols in olive leaves on platelet function. Nutr Metab Cardiovasc Dis. 2008 Feb;18(2):127-32. (29)

  • Zbidi H, Salido S, Altarejos J, et al. Olive tree wood phenolic compounds with human platelet antiaggregant properties. Blood Cells Mol Dis. 2009 May-Jun;42(3):279-85. (30)

Diabetes

The diabetic (and pre-diabetic) state of chronic blood sugar elevation imposes substantial oxidative stress throughout the body, triggering inflammation and tissue damage that rapidly accelerates aging.

Treatments for diabetes have two main goals: 1) lowering blood glucose to normal levels and 2) limiting the damage done by the inevitable blood sugar spikes that still occur.

Oleuropein has been found to lower blood sugar through several mechanisms. (31-32)  They slow the digestion of starches into simple sugars, slow absorption of those sugars from the intestine, and increase the uptake of glucose into tissues from the blood (31,32)  They protect tissues from the oxidant damage caused when glucose binds to proteins in the process called glycation.  They also increase levels of other natural antioxidant systems in the body, broadening the degree of protection. (32).  Human studies reveal that taking olive leaf resulted in significant reductions in hemoglobin A1c levels, the standard marker of long-term exposure to elevated blood sugar in diabetic people. (31) Supplementation also lowered fasting plasma insulin levels, an important point because chronic insulin elevations may contribute to diabetics’ higher cancer risks. (31,37)

References:

  • Wainstein J, Ganz T, Boaz M, et al. Olive leaf extract as a hypoglycemic agent in both human diabetic subjects and in rats. J Med Food. 2012 Jul;15(7):605-10. (31)

  • Gonzalez M, Zarzuelo A, Gamez MJ, Utrilla MP, Jimenez J, Osuna I. Hypoglycemic activity of olive leaf. Planta Med. 1992 Dec;58(6):513-5. (32)

  • Simon D, Balkau B. Diabetes mellitus, hyperglycaemia and cancer. Diabetes Metab. 2010 Jun;36(3):182-91. (37)

Arthritis

Olive leaf has long been used in the Mediterranean as a remedy for arthritis. Now, scientific evidence has proven that olive leaf can in fact interfere with the development of several different kinds of arthritis, including gout, rheumatoid arthritis, and osteoarthritis.

Gout is caused by the accumulation of uric acid crystals in joints, the byproducts of impaired recycling of DNA and RNA in cells. In a mechanism identical to that of allopurinol (the gold standard drug therapy for gout), oleuropein prevents the buildup of uric acid by inhibiting xanthine oxidase, the enzyme responsible for converting DNA and RNA into uric acid. (57).   Oleuropein has also been found to help prevent and treat symptoms of rheumatoid arthritis. When administered at the earliest sign of arthritis in animal models, oleuropein prevented symptoms from developing and also produced marked improvement in the microscopic appearance of joint tissue from affected animals. When administered after arthritis was fully developed, there was significant improvement in inflammatory changes to joints, compared with untreated animals. (58)  Oleuropein had similar benefits on osteoarthritis. In animal models of this degenerative joint disease, olive leaf extract improved joint swelling, improved the microscopic appearance of joint tissue, and prevented the production of inflammatory cytokines. (59)

References:

  • Flemmig J, Kuchta K, Arnhold J, Rauwald HW. Olea europaea leaf (Ph.Eur.) extract as well as several of its isolated phenolics inhibit the gout-related enzyme xanthine oxidase. Phytomedicine.2011 May 15;18(7):561-6. (57)

  • Impellizzeri D, Esposito E, Mazzon E, et al. Oleuropein aglycone, an olive oil compound, ameliorates development of arthritis caused by injection of collagen type II in mice. J Pharmacol Exp Ther.2011 Dec;339(3):859-69. (58)

  • Gong D, Geng C, Jiang L, Wang L, Yoshimura H, Zhong L. Mechanisms of olive leaf extract-ameliorated rat arthritis caused by kaolin and carrageenan. Phytother Res. 2012 Mar;26(3):397-402. (59)

Olive leaf extract has been shown to dispel protozoan-caused diseases, its not surprising its reputation as an anti-malarial dates back to the early 19th century. In the 1800s, physicians brewed olive leaves and administered the bitter tea to malaria patients. The doctors reported their patients improved after drinking this tea. (1)

The Upjohn researchers determined that oleuopein inhibited at least 56 disease-causing bacteria, viruses and protozoa, including the malaria-causing Plasmodium falciparum. The researchers also found it was effective against Vaccinia, a contagious viral disease of cattle, produced in humans by inoculation with cowpox virus to confer immunity against smallpox. (1)

References:

  • Walker, Morton MD. Natures Antibiotic: Olive Leaf Extract, Kensington Books, New York, 1997. pps. 65-68, 39, 149 (1)

References:

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2. Pallas E. Journal Universel des Sciences Medicales, tome xlix, p. 257, 1828.
3. Pallas. E. Receul de Memoires de Medecine, de Chirurgie, et de Pharmacie Militaires, vol xxiii, p. 152, 1827.
4. Pallas E. Receul de Memoires de Medecine, de Chirurgie, et de Pharmacie Militaires, vol xxvi, p. 159, 1829.
5. Etchells JL, Borg AF, Kittel ID, Bell TA, Fleming HP. Pure culture fermentation of green olives. Appl Microbiol 14, 1027—1041, 1966.
6. Fleming, HP, Etchells JL. Occurrence of an inhibitor of lactic acid bacteria in green olives. Appl Microbiol 15, 11781184, 1967.
7. Juven B, Samish Z, Henis Y, Jacoby B. Mechanism of enhancement of lactic acid fermentation of green olives by alkali and heat treatments. J Appl Bacteriol 31, 200—207, 1968.
8. Fleming HP, Walter WM, Etchells JL. Isolation of a bacterial inhibitor from green olives. Appl Microbiol 18, 856—860, 1969.
9. Panizzi L, Scarpati ML, Oriente G. Gazz Chim Ital 90, 1449, 1960.
10. Inouye H, Yoshida T, Tobita S, Tanaka K, Nishioka T. Tetrahedron Letters 28, 2459, 1970.
11. Vaughn RH. Lactic acid fermentation of cucumbers, sauerkraut and olives. In: Underkotler LA, Hickey RJ (Eds), Industrial Fermentations, Vol 2. New York: Chemical Publishing, 1954.
12. Moreno E, Perez J, Ramos-Cormenzana A, Martinez J. Microbios 51, 169—174, 1987.
13. Paredes MJ, Monteleolina-Sanchez M, Moreno E, Perez J, Ramos-Cormenzana A, Martinez J. Chemosphere 15, 659—664, 1986.
14. Paredes MJ, Moreno E, Ramos-Cormenzana A, Martiniz J. Chemosphere 16, 1557—1564, 1987.
15. Rodriguez MM, Perez J, Ramos-Cormenzana A, Martinez J. J Appl Bacteriol 64, 219—225, 1988
16. Pasquale AD, Monforte MT, Calabro ML. HPLC analysis of oleuropein and some flavonoids in leaf and bud of Olea Europaea L. Il Farmaco 46 (6): 803—815, 1991.
17. Cruess WV, Alsberg CL. The bitter glucoside of the olive. J Amer Chem Soc 56, 2115—2117, 1934.
18. Juven B, Samish Z, Henis Y. Identification of oleuropein as a natural inhibitor of lactic acid fermentation. Israel J Agr Res 18, 137—138, 1968.
19. Le Tutour B, Guedon D. Antioxidative activities of Olea europaea leaves and related phenolic compounds. Phytochem 31 (4), 1173—1178, 1992.
20. Fleming HP, Walter WM, Etchells JL. Antimicrobial properties of oleuropein and products of its hydrolysis. Appl Microbiol 26 (5), 777—782, 1973.
21. Tassou CC, Nychas GJE, Board RG. Effect of phenolic compounds and oleuropein on the germination of Bacillus cereus T spores. Biotech Appl Biochem 13, 231—237, 1991.
22. Renis HE. In vitro antiviral activity of calcium elenolate. Antimicrob Agents Chemother, p. 167—172, 1969.
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31. Muriana FJG, Ruiz-Gutierrez V, Vazquez CM. Influence of dietary cholesterol on polyunsaturated fatty acid composition, fluidity and membrane-bound enzymes in liver microsomes of rats fed olive and fish oil. Biochimie 74, 551—556, 1992.
32. Visioli F, Galli C. Oleuropein protects low density lipoprotein from oxidation. Life Sci 55 (24), 1965—1971, 1994.
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50. Letters received from consumers by East Park Research, Inc., Hendersen, Nevada, USA, August 1995 – March 1996.
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53. Information provided by the UK distributor of Eden Extract™, Tigon Limited, Loughborough, Leicestershire.

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