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PHCOG REV.: Plant Review
Olea europaea: A Phyto-Pharmacological Review
Md. Yaseen Khan*, Siddharth Panchal, Niraj Vyas, Amee Butani, Vimal Kumar
Department of Phytopharmaceuticals and Natural Products, Institute of Pharmacy,
Nirma University of Science and Technology, S.G. highway, Ahmedabad- 382 481.
*Corresponding author. Tel: +91-99040- 44934 E-mail address: mohammadyaseenkhan@gmail.com;
nirajvyas4me@yahoo.co.in
ABSTRACT –
Medicinal herbs are significant sources for treating various diseases. Olea europaea is used traditionally as diuretic, hypotensive,
emollient, laxative, febrifuge, skin cleanser, cholagogue, and also used for the treatment of urinary infections, gallstones,
bronchial asthma and diarrhoea. Several phytoconstituents have been isolated and identified from different parts of the plant
belonging to the category glycosides, secoiridoid, flavonoids and poly-unsaturated fatty acids. Many studies have been conducted
to prove its potential as anti-oxidant, anti-viral, anti-microbial, anti-diabetic and for cardiovascular disorders. The present
review aims toward forming a bridge between traditional use and modern therapeutics of Olea europaea.
KEY WORDS - Olea europaea, oleuropein, Phytochemistry, Pharmacotherapeutics.
INTRODUCTION
Alternative systems of medicine viz. Ayurveda, Siddha, and
Chinese Medicine have become more popular in recent years
(1). Medicinal herb is a biosynthetic laboratory, for chemical
compounds like glycosides, alkaloids, resins, oleoresins, etc.
These exert physiological and therapeutic effect (2). The
compounds that are responsible for medicinal property of the
drug are usually secondary metabolites. Olea europaea
preparations have been used widely in folk medicine in
European Mediterranean area, Arabia peninsula, India and
other tropical and subtropical regions, as diuretic,
hypotensive, emollient and for urinary and bladder infections
(3). Olive oil represents an important component of the
Mediterranean diet whose intake is greatly growing in
developed and developing countries for its known healing
effects (4).
Olea europaea (syn. Zaytoun, Jetun) belonging to the family
Oleaceae is a small evergreen tree, from 12 to 20 feet high,
with hoary, rigid branches, and a grayish bark. The leaves are
opposite, lanceolate, or ovate-lanceolate, mucronate, short-
petioled, green above, and hoary on the underside. The
flowers are small, in short, axillary, erect racemes, very
much shorter than the leaves. The corolla is short, white,
with 4 broad, ovate segments; the calyx short and 4-toothed.
The fruit is a drupe about the size of a damson, smooth,
purple, 2-celled, with a nauseous, bitter flesh, enclosing a
sharp-pointed stone. Virgin olive oil is the only edible oil of
great production obtained by physical methods from the fruit
of Olea europaea. It shows sensory characteristics and
nutritional properties that allows to distinguish it from the
others (5). In the current review, we will highlight on the
traditional uses and modern therapies of the Olea europaea.
TRADITIONAL MEDICINAL USES
Most of the plant parts of Olea europaea are used in
traditional system of medicine in world. Oil is taken with
lemon juice to treat gallstones (6). Leaves are taken orally for
stomach and intestinal diseases and used as mouth cleanser
(7). Decoctions of the dried fruit and of dried leaf are taken
orally for diarrhoea and to treat respiratory and urinary tract
infections (8). Hot water extract of the fresh leaves is taken
orally to treat hypertension and to induce diuresis (9, 10).
Seed oil is taken orally as a cholagogue, to remove gall
stones, in nephritis associated with the lead intoxication. To
prevent hair loss, oil is applied every night on the scalp then
shampooed the next morning (11). Seed oil is taken orally as a
laxative and applied externally as an emollient and pectoral
(12). Decoction of dried leaves is taken orally for diabetes
(13). Tincture of leaves is taken orally as a febrifuge (14).
Fruit is applied externally to fractured limb (15). Fruit is used
externally as a skin cleanser (16). Hot water extract of dried
plant is taken orally for bronchial asthma (17). Infusion of the
fresh leaf is taken orally for as an anti-inflammatory (18).
Fig: 1 Branch with ripe olives Fig: 2 Flowering olive branch Fig: 3 Olive flowers
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HO
OH
O
O O
COOH
O
O
OH
OH
HO
H
H
HO
H
H
HO
O
O O
COOH
O
O
OH
OH
HO
H
H
HO
H
H
PHYTOCHEMISTRY
Glucoside components in the olive (leaves and fruits)
Among the different components which are already known in
the olive plant, the first one is the oleuropein. This is the
most important component of the glucosidic fraction of the
Olea europaea from the quantitative point of view and from
the historical point of view. In fact, the oleuropein is the first
secoiridoid isolated from all over the world. In the oleuropein
molecule, both a mono-terpenic and an orhto-diphenolic unit
are present (19). Panizzi et al. (20) isolated oleuropein in the
50s. They determined its structure and established that this
compound was one of the most important compounds
responsible for the bitter taste of the fruits and the leaves of
olive plant. It was the active compound responsible for the
known hypotensive action of the extracts of the olive plant.
Recently the accurate quantitative determination of
oleuropein content in olive and olive oil was proposed by
Sindona el al (21).
The oleuropein 1 is a secoiridoid glucoside that esterifies a
dihydroxy-phenyl-ethyl alcohol. Two of its by-products are
also present in the olive plant together with the oleuropein 1
and the mono-demethyl-derivatives 2 and 3. Compound 2 is
demethyl-oleuropein, which differs from oleuropein 1 in
having a free carboxylic group on the pyranosic ring.
Compound 3 is the oleoside methyl ester, known also as a
glucoside of the elenolic acid, in which the carboxyl that
esterifies the dihydroxy-phenyl-ethanol in the oleuropein 1 is
here the free functionality. The two acid compounds 2 and 3
are two indicators of maturation of the olives. Their relative
quantity, as regards to the oleuropein 1, increases in fact as
soon as the maturation proceeds, while the quantity of
oleuropein decreases. This datum is in connection with the
increase of the activity of the hydrolytic enzymes with the
progress of the maturation, particularly to the activity of the
esterases, responsible of the hydrolysis of the two ester bonds
of the oleuropein (22). The ligstroside 4 (23) differs from the
oleuropein 1 in the presence of a tyrosol residue instead of
dihydroxy-phenyl-ethylic alcohol. The dimethylester of the
oleoside 5, also known as glucoside of the methylester of the
elenolic acid, contains the two acidic functions of the
oleuropein esterified with a residue of methanol (24). The
oleuroside 6 is an isomer of the oleuropein, differing (25)
from 1 in the exocyclic double bond position. Then several
glucosidic compounds are present in connection with the
dihydroxy-phenyl-ethanol. The first one is the cornoside 7, a
glucoside of a hemiquinoid isomer of the dihydroxy-phenyl-
ethyl alcohol (26). The others are the β-glucopyranosyl-
derivatives of dihydroxy-phenyl-ethanol 8a, 8b and 8c. The
structure of compound 8a has been demonstrated by
spectroscopic analysis by Bianco et al (27). Compounds 8b and
8c were previously described in O.europaea. Another new
compound isolated from the olive plant is the product 9, the
di-galactoside of a poly-unsaturated diester of the glycerol
(28). The particularly interesting datum of this structure is
that the poly-unsaturated acid that esterifies the glycerine is
α-linolenic acid. The product 9 is the principal component of
a group of glycosides of poly-unsaturated di-esters of
glycerine, present in the leaves and in the olives and whose
concentration seems to decrease with the maturation, even if
in a not marked way. In the end, two new esters of tyrosol 10
(29) and of hydroxyl-tyrosol 11 (30) have been isolated from
olives. Both compounds indicate the interesting metabolic
activity of O.europaea. Compound 10 is the oleic ester of
tyrosol and it appears to be present mainly in olives.
Compound 11 is the malic ester of hydroxy-tyrosol and is
another of ester of tyrosol derivatives present in O.europaea.
Structure of isolated phytoconstituents
1 2 3
4 5 6
HO
OH
O
O O
COOCH3
O
O
OH
OH
HO
H
H
HO
H
H
HO
O O
COOCH3
O
O
OH
OH
HO
H
H
HO
H
H
H3CO
O O
COOCH3
O
O
OH
OH
HO
H
H
HO
H
H
HO
OH
O
O O
COOCH3
O
O
OH
OH
HO
H
H
HO
H
H
6
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7 8a 8b
8c 9
PHARMACOLOGY
Cardiovascular disorders
Epidemiological data obtained from clinical studies have
consistently demonstrated that the Mediterranean diet, rich
in olive oil, fruits, vegetables, and grains is correlated with a
lower than average risk of coronary heart disease (31). The
natural antioxidants, including oleuropein, from the olive tree
may play a role in the prevention of cardiovascular diseases
through a decreased formation of atherosclerotic plaques by
inhibiting LDL oxidation (32). An olive leaf extract was
reported in a laboratory study to have vasodilating effects,
seemingly independent of vascular endothelial integrity (33).
Traditional uses support olive leaf and olive oil in
cardiovascular disease prevention (34, 35). Animal
experiments in rabbit and rat preparations found a
hypotensive effect of oleuropein, possibly via direct action on
smooth muscle. Oleuropeoside also may exert vasodilator
activity. Additionally, olive leaf extracts may possess
antispasmodic, vasodilator, and anti-arrhythmic properties
(36, 37).
Anti-viral activities
Olive leaf extract has reported antiviral activity, reportedly
caused by the constituent calcium elenolate, a derivative of
elenolic acid (38, 39). The isolated calcium salt of elenolic
acid was tested as a broad-spectrum antiviral agent active
against all viruses tested (40). Some viruses inhibited by
calcium elenolate in vitro include rhinovirus, myxoviruses,
Herpes simplex type I, Herpes simplex type II, Herpes zoster,
Encephalomyocarditis, Polio 1, 2, and 3, two strains of
leukemia virus, many strains of influenza and para-influenza
viruses (41,42 ,43). The mechanism of action of the antiviral
activity is reported to include (44):
• An ability to interfere with critical amino acid
production essential for viruses.
• An ability to contain viral infection and/or spread by
inactivating viruses or by preventing virus shedding,
budding, or assembly at the cell membrane.
• Ability to directly penetrate infected cells and stop viral
replication.
• In the case of retroviruses, it is able to neutralize the
production of reverse transcriptase and protease.
O
O
OH
OH
HO
H
H
HO
H
H
OH
OH
8a
OO
HO
HO
OH
H
H
OH
H
H
OH
OH
8 b
O
O
OH
OH
HO
H
H
HO
H
H
OH
OH
8 c
O
OH
10
HO
HO O
O
O
O
11
O
HO
O
O
OH
OH
HO
H
H
HO
H
H7
HC
H2C
O
O
O
O
CH2
O
OH
OH
OH
HO
O
O
OH
HO
HO
O
9
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• Stimulation of phagocytosis.
Anti-microbial activities
Olive leaves are known to resist insect and microbial attack,
and in-vitro studies have been conducted to establish the
range of activity of olive leaf extracts (45,46).Olive leaf
extract has been reported to be an effective antimicrobial
agent against a variety of pathogens, including Salmonella
typhi, Vibrio parahaemolyticus, and Staphylococcus aureus
(including penicillin-resistant strains); and Klebsiella
pneumonia, and Escherichia coli, causal agents of intestinal
or respiratory tract infections in humans (47). Olive leaf could
be considered a potentially effective antimicrobial agent for
the treatment of intestinal or respiratory tract infections. The
component usually associated with olive leaf’s antimicrobial
properties is oleuropein (48, 49). Oleuropein has also been
reported to directly stimulate macrophage activation in
laboratory studies (50). Hydroxytyrosol demonstrated broader
antimicrobial activity than oleuropein and is comparable to
ampicillin and erythromycin in spectrum and potency (51).
Anti-oxidant activities
Olive leaf has antioxidant properties associated with
oleuropein. Caffeic acid was also reported to have antioxidant
activity through the scavenging of superoxide anion (52).
Olive leaf has been reported to have anti-complement in
vitro, and is a proposed mechanism for its anti-inflammatory
effects (53). Oleuropein, an antioxidant, has been reported to
decrease the oxidation of LDL cholesterol (54). Oxidized LDL
is the most damaging form of cholesterol and can initiate
damage to arterial tissues, thereby promoting atherosclerosis.
Olive leaf has been reported to inhibit platelet aggregation
and production of thromboxane A2 (a stimulator of platelet
aggregation with vasodilatory effects) (55). Also of interest, is
a recent study reporting that olive leaf extract inhibited both
angiotensin converting enzymes (56). In-vitro and animal
experiments have been conducted to demonstrate the
antioxidant activity of olive leaf extracts. In rat epithelial
cells stimulated with cytokines, a concentrated polyphenol
extract reduced nitrite concentration and free radical
production (57). Rabbits with induced diabetes showed a
decrease in oxidative stress markers when treated with
oleuropein (58). Other experiments support the antioxidant
activity of the phenols oleuropein and hydroxytyrosol (59-62).
Hypolipedemic activities
Studies in laboratory animals have reported hypoglycemic and
hypolipidemic activity of olive leaf (63, 64). The active
constituent was reported to be oleuropein, with a proposed
mechanism of action of potentiation of glucose-induced
insulin release, and an increase in peripheral blood glucose
uptake.
Anti- diabetic activities
The hypoglycemic activity of olive leaf has been
demonstrated in animals. In rabbits with induced diabetes, an
ethanol extract of olive leaf decreased blood glucose.
Suggested mechanisms include potentiation of glucose-
induced insulin release and increased peripheral uptake of
glucose (65, 66).
Thyroid activities
An aqueous extract of olive leaf administered to rats for 14
days increased T 3 levels and reduced circulating thyroid-
stimulating hormone levels, possibly via a feedback
mechanism (67).
CONCLUSION
Plants have been used as medicines since the time of
immemorial, among which is Olea europaea whose products
are widely available in the market for the treatment of
various ailments. It has proved it efficacy in the management
of various complex diseases including diabetes, cardiovascular
disorders, viral and microbial infections but still a lot of work
is to be done for exploring the evidences for other traditional
uses of the plant.
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