Abacate - efeitos na sindrome metabolica

Prévia do material em texto

REVIEW
Effects of Avocado (Persea americana) on
Metabolic Syndrome: A Comprehensive
Systematic Review
Jamshid Tabeshpour,1,2 Bibi Marjan Razavi3 and Hossein Hosseinzadeh4*
1Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
2Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
3Targeted Drug Delivery Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University
of Medical Sciences, Mashhad, Iran
4Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of
Medical Sciences, Mashhad, Iran
Metabolic syndrome (MetS) is a clustering of risk factors including high blood glucose, dyslipidemia,
hypertension, and obesity that lead to the increased risk of type 2 diabetes mellitus and cardiovascular diseases
(CVDs), which are among leading causes of death in the world. Metabolic syndrome increases the risk of type 2
diabetes mellitus and CVDs by approximately five and three folds, respectively. Therefore, it is of vital
importance to manage such conditions with herbal options which have less undesirable adverse effects and
may be more efficacious in comparison with synthetic options. Avocado is a well-known source of carotenoids,
minerals, phenolics, vitamins, and fatty acids. The lipid-lowering, antihypertensive, antidiabetic, anti-obesity,
antithrombotic, antiatherosclerotic, and cardioprotective effects of avocado have been demonstrated in several
studies. In this review, we aimed to find out avocado’s pharmacological effects on different components of MetS.
Moreover, this review report is performed on the MetS effects of peel, seed, flesh, and leaves of avocado.
Copyright © 2017 John Wiley & Sons, Ltd.
Keywords: avocado; Persea americana; metabolic syndrome; cardiovascular diseases; obesity; diabetes.
Abbreviations: A1CE, angiotensin 1 converting enzyme; ADI, adiposity index; AID, alloxan-induced diabetic; ALP, alkaline
phosphatase; ALT, alanine transaminase; APTT, activated partial thromboplastin time; AST, aspartate transaminase; BGLs, blood
glucose levels; BMI, body mass index; BP, blood pressure; CAT, catalase; CVDs, cardiovascular diseases; DPPH, l, l-diphenyl,
2-picrylhydrazyl; FASN, fatty acid synthase; FBG, fasting blood glucose; GPx, glutathione peroxidase; GR, glutathione reductase;
HCD, high-cholesterol diet; HCh, hypercholesterolemic; HFD, high-fat diet; HR, heart rate; LPL, lipoprotein lipase; MDA,
malondialdehyde; MetS, Metabolic syndrome; P. Americana, Persea Americana; PLs, phospholipids; PPAR-γ, peroxisome
proliferator-activated receptor-γ; PT, prothrombin time; SID, streptozotocin-induced diabetic; SOD, superoxide dismutase; T2DM,
type 2 diabetes mellitus; TC, total cholesterol; TFP, total fat pad mass; TG, triglyceride, LDL-C, low-density lipoprotein cholesterol,
HDL-C, high-density lipoprotein cholesterol; VLDL, very-low-density lipoprotein
INTRODUCTION
Metabolic syndrome (MetS) is a clinical entity markedly
heterogeneous, characterized by the co-occurrence
of multiple changes in obesity, insulin-resistance,
hypertension, and dyslipidemia, correlated with an
enhanced risk of developing cardiovascular diseases
(CVDs) and type 2 diabetes mellitus (T2DM) (Wu et al.,
2010). Metabolic syndrome is regarded as an increasing
cause of morbidity and mortality in both developed and
developing countries (Smith and Ryckman, 2015). There
are several criteria set out by different associations for
MetS definition and diagnosis. The most generally
accepted definition consists of three or more of the
following indicators: blood pressure (BP) > 135/
85 mmHg, fasting blood glucose (FBG) > 6.1 mmol/L,
high-density lipoprotein cholesterol (HDL) < 1.0 mmol/
L (male) or <1.3 mmol/L (female), triglyceride
(TG) > 1.7 mmol/L and waist circumference > 102 cm
(male) or >88 cm (female) (Malik et al., 2004; Grundy
et al., 2005).
Medicinal plants have been used as an accepted
complementary medical option for centuries to improve
the health condition of the folk through decreasing the
adverse effects and costs of the synthetic medicines
(Hassani et al., 2016; Rouhi-Boroujeni et al., 2015). In
developing countries, more than 80% of the population
use traditional medicinal plants to treat a variety of
diseases (Rouhi-Boroujeni et al., 2015). Although
herbs are regarded as ‘natural’ and safe, many different
side effects have been reported because of active
ingredients, contaminants, or interactions with drugs.
Moreover, there is limited evidence regarding the use
of herbal medicines during pregnancy as well as in
pediatric and geriatric populations (Izzo et al., 2016).
These days, plants are regarded as a valuable source to
treat the various components of MetS including obesity,
* Correspondence to: Hossein Hosseinzadeh, Pharmaceutical Research
Center, Department of Pharmacodynamics and Toxicology, School of
Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
E-mail: hosseinzadehh@mums.ac.ir
PHYTOTHERAPY RESEARCH
Phytother. Res. (2017)
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/ptr.5805
Copyright © 2017 John Wiley & Sons, Ltd.
Received 16 January 2017
Revised 27 February 2017
Accepted 02 March 2017
http://orcid.org/0000-0002-3483-851X
hyperglycemia, hypertension, and dyslipidemia. In this
regard, it is very important to find and utilize medicinal
plants, and their constituents with beneficial effects on
MetS to replace with synthetic medicines. For instance,
cinnamon; garlic; grape; black cumin, saffron and its
constituent, thymoquinone; and rutin have shown
promising effects on MetS (Mollazadeh and
Hosseinzadeh, 2016; Hosseini and Hosseinzadeh, 2015;
Akaberi and Hosseinzadeh, 2016; Razavi and
Hosseinzadeh, 2014; Hosseinzadeh and Nassiri-Asl,
2014; Razavi and Hosseinzadeh, 2016). Avocado with
the scientific name of Persea americana (P. americana),
and other names such as ‘alligator pear’, ‘avocato’,
‘ahuacate’ etc., from the Lauraceae family, originated
in Mexico and Central or South America, is an
evergreen tree that can reach the height of 10 m or more
(Dreher and Davenport, 2013; Lacerda et al., 2015). It is
also known as ‘alligator pear’ or ‘butter pear’ (Lacerda
et al., 2015). Avocado is consumed, not only for its
flavor, but also for its high nutritional value and
beneficial health effects (Meyer and Terry, 2010)
including hypoglycaemic (Ezejiofor et al., 2013a),
antihypertensive (Dzeufiet et al., 2014), antioxidant
(Nagaraj et al., 2010), anti-obesity (Monika and
Geetha, 2016), hypolipidemic (Pahua-Ramos et al.,
2012) (Fig. 4), antilithiasis (Wientarsih et al., 2012),
anticonvulsant (Ojewole and Amabeoku, 2006),
antimicrobial (Pradeep et al., 2012), antiprotozoal and
antimycobacterial (Jiménez-Arellanes et al., 2013),
hepatoprotective (Mahmoed and Rezq, 2013),
antiosteoarthritis (Christiansen et al., 2015) and
chemo-protective (Paul et al., 2011).
Avocado composition analysis has shown that this
plant is nutritionally valuable. The most important
bioactive phytochemicals of avocado are categorized
into: Carotenoids, fatty acids, minerals, phenolics
and polyphenolic compounds, phytosterols and
phytostanols, proteins, seven-carbon sugars, and
vitamins (Table 1). The pharmacologically active
constituents of this plant have been also shown to
possess antifungal, antiinflammatory, and antioxidant
activity in some studies (Lu et al., 2005; Sudhir, 2005).
Furthermore, daily consumption of phytosterols and
phytostanols decreases the serum levels of cholesterol,
because of similar structures, leading to the prevention
of CVDs and also potential protection in the number
of cancer development (Awad and Fink, 2000;
Piironen et al., 2000; Kritchevsky and Chen, 2005).
For instance, an in vitro study showed that the avocado
pulp, specifically tocopherols, lutein, and other
carotenoids (as active constituents), possess growth
inhibitory effects against cancer (Luet al., 2009). Fig. 2
shows the structural comparison of the bioactive
constituents of avocado such as phytosterols,
phytostanols, and cholesterol. Some of the most
abundant pharmacologically active constituents of
avocado phytochemicals are structurally shown in
Fig. 3. Our review aimed to evaluate the effect of
different bioactive phytochemicals of avocado on
various components of MetS including T2DM,
hypertension, dyslipidemia, and obesity, and to
describe different mechanisms of action. Moreover, in
this review, 186 articles were found, among which 129
were revised and included (Fig. 1).
Effect on high glucose level
Type 2 diabetes mellitus is known as a metabolic
disorder which results from a failure in insulin secretion,
action or both (Rao and Adinew, 2011). This can lead
to micro-vascular and macro-vascular difficulties
which chronically cause the malfunctioning of central
and peripheral nervous system, kidney, eye, and
cardiovascular system (Brahmachari, 2011). Besides, it
is one of the main causes of mortality, morbidity, and
health center costs in the world. According to the global
reports on diabetes by the World Health Organization,
the number of people suffering from diabetes has been
108 million in 1980 which has augmented to 422 million
in 2014 (Collaboration, NCDRF, 2016). Many studies
have been accomplished on the antidiabetic effects of
avocado in different experimental models (human,
in vivo and in vitro) which are discussed in the
succeeding text (Table 2).
Table 1. The most abundant bioactive components of avocado
Categories Bioactive constituents References
Carotenoids Lutein, β-cryptoxanthin, zeaxanthin, α-carotene, and
β-carotene
(Koh et al., 2004)
Fatty acids Monounsaturated (oleic and palmitic acids), unsaturated
(linoleic, palmitoleic, and linolenic acids)
(Ozdemir and Topuz, 2004; Vekiari et al.,
2004)
Minerals Calcium, iron, magnesium, phosphorus, potassium,
sodium, zinc, copper, manganese, and selenium
(Dreher and Davenport, 2013)
Phenolics and polyphenolic
compounds
Phenolic acids (hydroxybenzoic and hydrocinnamic acids),
flavonoids (rutin), stilbenes (resveratrol), coumarins, and
tannins (tannic acid)
(Golan et al., 1977; Kahn, 1983;
Rodríguez-Carpena et al., 2011)
Phytosterols and phytostanols β-sitosterol, campesterol, stigmasterol (Moghadasian and Frohlich, 1999;
Dreher and Davenport, 2013)β-sitostanol, campestanol, and stigmastanol
Proteins Asparagine, aspartic acid, glutamine, and glutamic acid (Ahmed and Barmore 1980)
Seven-carbon sugars D-mannoheptulose and perseitol (its reduced form polyol) (Liu et al., 1999)
Vitamins Vitamin A, vitamin B (B1, B2, B3, B5, B6, B12, folate, and
choline), betaine, vitamin C, vitamin E (α-tocopherol,
β-tocopherol, γ-tocopherol, δ-tocopherol), and vitamin K1
(Dreher and Davenport, 2013)
J. TABESHPOUR ET AL.
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
Clinical studies
In a randomized crossover study, 12 women with T2DM
received two different diets. One received a high
monounsaturated fatty acids diet (including oleic acid
from avocado and olive oil) and the other received
a high-complex carbohydrates diet for 4 weeks.
The results showed that the first diet maintained
an adequate glycemic control and offered a good
management alternative (Lerman-Garber et al., 1994).
Another randomized clinical trial, investigated on 26
healthy overweight subjects, revealed that consumption
of half of a Hass avocado significantly reduced the blood
insulin and glucagon-like peptide-1 levels. It was
concluded that D-mannoheptulose may be responsible
for hypoglycemic effect by glycolysis decline via
hexokinase inhibition and weight control via appetite
reduction (Sabaté et al., 2015). In addition, the results
of Wien et al. investigation on healthy overweight adults
showed that avocado in lunch meal attenuated the rise
in postprandial blood insulin levels 30 min after start
of the lunch meal and diminished the desire to eat as
compared with the avocado-free control which could
be because of its anti-obesity effect (Wien et al., 2013).
In vivo studies
Lima et al. investigated the hypoglycemic properties of
avocado and observed that oral administration of the
Figure 2. The structural comparison of phytosterols, phytostanols, and cholesterol (the bioactive constituents of avocado).
Figure 1. Flow chart of systematic literature search showing the included and excluded studies.
AVOCADO AND METABOLIC SYNDROME
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
hydroalcoholic extract of the leaves (0.15 and
0.3 g/kg/day, for 4 weeks) to streptozotocin-induced
diabetic (SID) rats, reduced blood glucose levels
(BGLs) while the metabolic state of the animals
improved. They proposed that the mechanism of this
effect could be regulating the glucose uptake in liver
and muscles through Akt/PKB activation and
consequently restoring the intracellular energy balance
(Lima et al., 2012). The SID rats which received
ethanolic extract of P. americana fruit (300 mg/kg/day,
orally for 4 weeks), showed a decrease in the raised
BGLs, glycosylated hemoglobin (Hb), blood urea,
and serum creatinine. It also increased the levels of
plasma insulin and Hb (Rao and Adinew, 2011).
Streptozotocin-induced diabetic rats were orally treated
with avocado oil (1 mL/250 g/day, for 3 months).
Avocado oil diminished reactive oxygen species levels,
lipid peroxidation, oxidative stress, the activity of
complex III of the electron transport chain, and TG
levels in the brain while improved the reduced
glutathione/oxidized glutathione ratio and brain
mitochondrial function (Ortiz-Avila et al., 2015a).
Furthermore, the hypoglycemic activity of n-hexane
fraction from hydro-methanolic (2:3) extract of P.
americana fruit (300 mg/kg, orally for 8 weeks) was
evaluated in SID rats. Body weight, serum levels of
insulin, hepatic, and skeletal muscle glycogen, activities
of hexokinase and glucose-6-phosphate dehydrogenase
enzymes in liver, kidney, skeletal muscle, and cardiac
muscle increased. While a significant decrease in FBG
levels, glycosylated Hb (which is one of the most
important indicators of diabetic condition) and the
reduced activities of aspartate transaminase (AST) and
alanine transaminase (ALT) enzymes in serum were
observed (Thenmozhi et al., 2012). The glucose
tolerance and insulin resistance reducing effects of
avocado oil were investigated in sucrose-induced
diabetic rats which can result from adding 5–20% of
avocado oil to the diet (Del Toro-Equihua et al., 2016).
Aqueous extract of avocado seed (300 and 600 mg/kg)
showed a significant reduction in BGLs, especially with
the higher dose, in alloxan-induced diabetic (AID) rats.
The histological investigation revealed a degenerative
effect on the pancreatic islet cells in diabetic rats which
indicated that the aqueous extract of avocado seed had
a protective effect on these cells. This study confirmed
the significant hypoglycemic effect of avocado seed
(Edem et al., 2009). The antidiabetic effect of the
aqueous extract of avocado seed (400, 800 and
1200 mg/kg) was also investigated in AID rats and a
significant decrease in FBG was observed (Alhassan
et al., 2012).
The hypoglycemic and tissue-protective effects of the
hot-water extract of P. americana seeds (20, 30, 40 g/L,
for 3 weeks) were investigated in AID rats. It was shown
that the extract had a significant hypoglycaemic effect
and reversed the histopathological damage that
occurred in AID rats, comparable with the effects of
glibenclamide (Ezejiofor et al., 2013b). Reduction in
oxidative stress, lipid peroxidation, and reactive oxygen
species production was observed in the liver
mitochondria of the SID rats which were treated with
avocado oil (4 mL/kg) for 3 months. The oil also
normalized the serum levels of cholesterol, TG, and
induced weight gain. This study showed that avocado
oil attenuated the harmful effects of diabetes on
oxidative condition of liver mitochondria (Ortiz-Avila
et al., 2015b). Antia et al.indicated that the aqueous leaf
Figure 3. Some of pharmacologically active constituents of
avocado.
Figure 4. Experimentally observed effects of different parts of avocado in respect of pharmacological actions. A: leaves. B: pulp. C: oil. D:
peel. E: seed.
J. TABESHPOUR ET AL.
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
Table 2. Antidiabetic effects of avocado
Part(s) of the plant
used/ Extract(s) Active constituents
Dosage (mg/kg/day)/
Route/ duration
of treatment
Experimental
model Outcome Reference
Clinical trials
Oil/Avocado oil-
enhanced diet
MUFA (oleic acid) Not mentioned/p.o./
4 weeks
T2DM humans ↓FBG (Lerman-Garber et al.,
1994)
Hass/Avocado oil-
enhanced diet
D-mannoheptulose 0.5 Hass avocado/p.o.
/3 days
Healthy overweight
humans
↑Leptin (Sabaté et al., 2015)
↓Blood insulin levels
↓GLP-1
Animal studies
Leaves/Hydroalcoholic flavonoids 150 and 300/p.o./
4 weeks
SID rats Activation of Akt/PKB (Lima et al., 2012)
Pulp/Ethanolic Fatty acids and
amino aids
300/p.o./4 weeks SID rats ↑Plasma insulin (Rao and Adinew,
2011)↑Hb
↓BGLs and
Glycosylated Hb
↓Blood urea
↓Serum creatinine
↓AST, ALT and ALP
Oil/Not mentioned Carotenoids,
tocopherols,
chlorophylls,
vitamins, and oleic
acid
4 (mL/kg)/p.o./
3 months
SID rats ↑GSH/GSSG ratio (Ortiz-Avila et al.,
2015a)↓ROS
↓Complex III activity
↓TG
Pulp/Hydro-methanolic Not mentioned 300/p.o./2 months SID rats ↑Body weight (Thenmozhi et al.,
2012)↑Insulin and Glycogen
↑Hexokinase and
G6PD activities
↓FBG
↓Glycosylated Hb
↓AST and ALT
Oil/Avocado oil-
enhanced diet
MUFAs and PUFAs 5% (50 g oil + 950 g
feed
pellets),10%,20%,
30%/p.o./2 months
Sucrose-induced
diabetic rats
↓Glucose tolerance (Del Toro-Equihua
et al., 2016)↓Insulin resistance
Seeds/Aqueous Not mentioned 300 and 600/p.o./
3 weeks
AID rats ↓BGLs (Edem et al., 2009)
Seeds/Aqueous Flavonoids, minerals 400, 800, and 1200/p.
o./4 weeks
AID rats ↓FBG (Alhassan et al.,
2012)
Seeds/Aqueous Flavonoids etc. 20, 30, 40 (g/L)/p.o.
/3 weeks
AID rats ↑Body weight (Ezejiofor et al.,
2013b)↓FBG
Oil/Avocado oil-
enhanced diet
Oleic acid 4 (mL/kg)/p.o./
3 months
SID rats ↑Body weight (Ortiz-Avila et al.,
2015b)↓Oxidative stress
↓Lipid peroxidation
↓ROS production
↓Cholesterol and TG
Leaves/Aqueous Saponins, tannins,
phlobatannins,
flavonoids,
alkaloids, and
polysaccharides
100, 150, and 200/p.
o./1 week
AID rats ↓BGLs (Antia et al., 2005)
Leaves/Ethanolic Not mentioned Not mentioned/p.o.
/6 weeks
SID rats ↑Hepatic glycogen (Gondwe et al., 2007)
↓FBG
Seeds/Ethanolic Not mentioned 450 and 900/p.o./Not
mentioned
Normal and AID rats ↓BGLs (Edem, 2009)
Leaves/Aqueous
and methanolic
Not mentioned 10/p.o./10 weeks HCD rats ↓BGLs (Brai et al., 2007b)
↓TC
↓LDL-C
(Continues)
AVOCADO AND METABOLIC SYNDROME
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
extract of avocado (100, 150, and 200 mg/kg, for 1 week)
significantly reduced the BGLs in AID rats (Antia et al.,
2005). In a study, it was demonstrated that P. americana
leaf ethanolic extracts exerted hypoglycemic effects via
increase in hepatic glycogen concentrations and
decrease in FBG in a dose-dependent fashion in SID
rats (Gondwe et al., 2007). The effect of ethanolic seed
extracts of P. americana at the doses of 450 and
900 mg/kg on normal and AID rats was investigated in
another study. The extracts consumption significantly
reduced BGLs in AID rats in a dose-dependent manner
and to a lesser extent in normal rats. This also confirms
the antidiabetic effect of this plant (Edem, 2009). The
hypoglycemic and hypercholesterolemic (HCh) effect
of P. americana leaf extracts (10 mg/kg, for 8 weeks)
were investigated in high-cholesterol diet (HCD)
rats. Aqueous and methanolic extracts induced a
decrease in total cholesterol (TC) and low-density
lipoprotein cholesterol (LDL-C) while plasma HDL-C
concentrations increased significantly. This could be an
alternative approach in the management of
atherosclerosis (Brai et al., 2007b).
In vitro studies
The antidiabetic effect of avocado was assessed in an
in vitro model of rat’s pancreas (tissue homogenates).
The aqueous extracts of leaves, peel, flesh, and seed
of avocado inhibited α-amylase (in the range of
0–0.164 mg/mL), α-glucosidase (in the range of
0–0.4 mg/mL), and the production of malondialdehyde
(MDA) (in the range of 0–0.313 mg/mL). They also
showed NO° and 2, 20-azino-bis (3-ethylbenzthiazoline-
6-sulphonic acid) radical scavenging activity, which can
be considered as one of the possible mechanisms of
T2DM management in a dose-dependent way (Ajani
and Olanrewaju, 2014). Besides, the methanolic and
aqueous extracts of avocado leaves indicated α-amylase
and α-glucosidase inhibitory activities in an in vitro
model. They showed that avocado leaves could
be considered as a potential source for diabetes
management (Uysal et al., 2015). The P. americana
leaves were examined for protein tyrosine phosphatase
1B inhibitory activity which is a relevant mechanism
involved in insulin resistance in T2DM. This inhibitory
effect of the extract was concentration-dependent
(0.01–300 μg/mL) (Marrero-Faz et al., 2014). In another
study, it was shown that avocado had a low glycemic
index, potent antioxidant activity, α-amylase and α-
glucosidase inhibition activities, which can be the
possible mechanisms of avocado antidiabetic effects
(Oboh et al., 2015). In an in vitro model, it was
demonstrated that avocado affected the glucose
diffusion across the gastrointestinal tract and decreased
in vitro glucose movement more than 50% (Gallagher
et al., 2003).
In vitro studies, consistent with clinical and in vivo
experiments, revealed that avocado showed antidiabetic
effects via regulating the glucose uptake in liver and
reducing glucose tolerance and insulin resistance.
EFFECT ON LIPID PROFILE
Dyslipidemia is described as high levels of lipids
(cholesterol, triglycerides, or both) carried by
lipoproteins in the blood, and is a common risk factor
of CVDs (Miller, 2009). It is defined as high cholesterol
>200 mg/dL, low HDL < 40 mg/dL, and high
TG ≥ 150 mg/dL (Fatema et al., 2016). More than 17
million people die annually from CVDs. It is also
estimated that by 2030, over 23 million people will
die from CVDs each year (Mackay et al., 2004).
The consumption of lipid-lowering medications may
bring about some adverse effects (Hosseini and
Hosseinzadeh, 2015). There is evidence that avocado
and some of its pharmacologically active constituents
possess lipid-lowering and antihyperlipidemic effects
(Table 3).
Table 2. (Continued)
Part(s) of the plant
used/ Extract(s) Active constituents
Dosage (mg/kg/day)/
Route/ duration
of treatment
Experimental
model Outcome Reference
In vitro studies
Leaves, peel, flesh,
and seeds/Aqueous
Bioactive phenolics 0–0.164, 0–0.4,
0–0.313 (mg/mL)/Not
mentioned
Rat’s pancreas
tissue homogenates
Inhibition of
α-amylase,
α-glucosidase
(Ajani and
Olanrewaju, 2014)
↓MDA
Leaves/Aqueous
and methanolic
MUFAs Not mentioned/Not
mentioned
Gas
chromatography
Inhibition of
α-amylase and
α-glucosidase
(Uysal et al., 2015)
Leaves/Aqueous Tannins and
terpenoid glycosides
0.01–300(μg/mL)/Not
mentioned
PTP1B human
recombinant 96
microplates
Inhibition of PTP1B (Marrero-Faz et al.,
2014)
Abbreviations. MUFAs, monounsaturated fatty acids; p.o., oral route; T2DM, type 2 diabetes mellitus; FBG, fasting blood glucose; GLP-1,
glucagon-like peptide-1; SID, streptozotocin-induced diabetic; Akt/PKB, Akt/Protein Kinase B; Hb, hemoglobin; BGLs, blood glucose levels;
AST, aspartate transaminase; ALT, alanine transaminase; ALP, alkaline phosphatase; GSH/GSSG, reduced glutathione/oxidized glutathione;
ROS, reactive oxygen species; TG, triglyceride; G6PD, glucose-6-phosphate dehydrogenase; PUFAs, polyunsaturated fatty acids; AID,
alloxan-induced diabetic; HCD, high-cholesterol diet; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; MDA,
malondialdehyde; PTP1B, protein tyrosine phosphatase 1B.
J. TABESHPOUR ET AL.Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
Ta
bl
e
3.
H
yp
ol
ip
id
em
ic
ef
fe
ct
s
of
av
oc
ad
o
P
ar
t(
s)
of
th
e
pl
an
t
us
ed
/
Ex
tr
ac
t(
s)
A
ct
iv
e
co
ns
ti
tu
en
ts
D
os
ag
e
(m
g/
kg
/d
ay
)/
R
ou
te
/
du
ra
ti
on
of
tr
ea
tm
en
t
Ex
pe
ri
m
en
ta
lm
od
el
O
ut
co
m
e
R
ef
er
en
ce
C
lin
ic
al
tr
ia
ls
P
ul
p/
N
ot
m
en
ti
on
ed
M
U
FA
s
0
.5
to
1
.5
av
oc
ad
os
/p
.o
.
/3
w
ee
ks
H
um
an
s
H
D
L-
C
(n
o
ch
an
ge
)
(C
ol
qu
ho
un
et
al
.,
1
9
9
2
)
A
po
-A
1
(n
o
ch
an
ge
)
↓T
C
↓L
D
L-
C
↓A
po
B
H
as
s/
N
ot
m
en
ti
on
ed
M
U
FA
s
1
3
6
g/
p.
o.
/5
w
ee
ks
O
be
se
or
ov
er
w
ei
gh
t
hu
m
an
s
↓L
D
L
pa
rt
ic
le
nu
m
be
r
(W
an
g
et
al
.,
2
0
1
5
)
↓s
m
al
ld
en
se
LD
L-
C
↓r
at
io
of
LD
L/
H
D
L
A
vo
ca
do
/A
vo
ca
do
-e
nr
ic
he
d
di
et
M
U
FA
s
7
5
%
av
oc
ad
o-
de
ri
ve
d
M
U
FA
s/
p.
o.
/4
w
ee
ks
D
ys
lip
id
em
ic
pa
ti
en
ts
↑H
D
L-
C
(C
ar
ra
nz
a
et
al
.,
1
9
9
5
)
↓T
G
,
T
C
,
an
d
LD
L-
C
A
vo
ca
do
/A
vo
ca
do
-e
nr
ic
he
d
di
et
M
U
FA
s
7
5
%
av
oc
ad
o-
de
ri
ve
d
M
U
FA
s/
p.
o.
/2
w
ee
ks
H
ea
lt
hy
vo
lu
nt
ee
rs
↑H
D
L-
C
(A
lv
iz
ou
ri
-M
uñ
oz
et
al
.,
1
9
9
2
)
↓T
G
,
T
C
,
an
d
LD
L-
C
A
vo
ca
do
/A
vo
ca
do
-e
nr
ic
he
d
di
et
M
U
FA
s
2
0
0
0
K
ca
l(
lip
id
s
5
3
%
,
M
U
FA
s
4
9
g,
sa
tu
ra
te
d/
un
sa
tu
ra
te
d
ra
ti
o
=
0
.5
4
)/
p.
o.
/o
ne
w
ee
k
H
ea
lt
hy
no
rm
ol
ip
id
em
ic
vo
lu
nt
ee
rs
an
d
H
C
h
pa
ti
en
ts
↓T
G
(L
óp
ez
Le
de
sm
a
et
al
.,
1
9
9
6
)
↓T
C
↓L
D
L-
C
A
vo
ca
do
/A
vo
ca
do
-e
nr
ic
he
d
di
et
M
U
FA
s
7
5
%
av
oc
ad
o-
de
ri
ve
d
M
U
FA
s/
p.
o.
/4
w
ee
ks
D
ys
lip
id
em
ic
pa
ti
en
ts
↓T
G
(C
ar
ra
nz
a-
M
ad
ri
ga
le
t
al
.,
1
9
9
7
)
↓L
D
L-
C
Fr
ui
ts
/A
vo
ca
do
-e
nr
ic
he
d
di
et
Fa
tt
y
ac
id
s
0
.5
to
1
.5
av
oc
ad
os
/p
.o
.
/8
w
ee
ks
M
al
e
pa
ti
en
ts
↓T
C
(G
ra
nt
,
1
9
6
0
)
↓S
er
um
P
Ls
A
vo
ca
do
/A
vo
ca
do
-e
nr
ic
he
d
di
et
N
ot
m
en
ti
on
ed
1
av
oc
ad
o
(2
0
0
g)
/p
.o
./
6
w
ee
ks
O
ve
rw
ei
gh
t
an
d
ob
es
e
vo
lu
nt
ee
rs
↓B
od
y
w
ei
gh
t
(P
ie
te
rs
e,
2
0
0
3
)
↓B
M
I
↓P
er
ce
nt
ag
e
bo
dy
fa
t
A
vo
ca
do
an
d
av
oc
ad
o
oi
l/
A
vo
ca
do
-e
nr
ic
he
d
di
et
C
ar
ot
en
oi
ds
7
5
an
d
1
5
0
g
av
oc
ad
os
or
2
4
g
av
oc
ad
o
oi
l/p
.o
./
8
w
ee
ks
H
ea
lt
hy
vo
lu
nt
ee
rs
↑A
bs
or
pt
io
n
of
ly
co
pe
ne
,
β-
ca
ro
te
ne
α-
ca
ro
te
ne
,
an
d
lu
te
in
(U
nl
u
et
al
.,
2
0
0
5
)
A
ni
m
al
st
ud
ie
s
A
vo
ca
do
pa
st
e/
N
ot
m
en
ti
on
ed
C
ar
ot
en
oi
ds
,
po
ly
ph
en
ol
s,
ch
lo
ro
ph
yl
ls
,
an
d
fi
be
r
2
0
0
0
/p
.o
./
7
w
ee
ks
H
C
D
an
d
hi
gh
-f
ru
ct
os
e
di
et
ra
ts
↓T
G
,
T
C
an
d
LD
L-
C
(P
ah
ua
-R
am
os
et
al
.,
2
0
1
4
)
↓A
S
T
↓A
LT
S
ee
ds
/E
th
an
ol
ic
N
ot
m
en
ti
on
ed
4
5
0
an
d
9
0
0
/p
.o
./
2
w
ee
ks
A
ID
ra
ts
↑H
D
L-
C
(E
de
m
,
2
0
1
0
)
↓T
G
,
T
C
,
an
d
LD
L-
C
S
ee
d
oi
l/O
rg
an
ic
so
lv
en
t
N
ot
m
en
ti
on
ed
1
0
%
(w
/w
)/
p.
o.
/4
w
ee
ks
Fe
m
al
e
ra
ts
↓T
ot
al
liv
er
lip
og
en
es
is
(W
er
m
an
et
al
.,
1
9
9
1
)
↓P
Ls
an
d
T
G
sy
nt
he
si
s
↓P
ro
te
in
co
nt
en
t
of
V
LD
L
an
d
H
D
L-
C
fr
ac
ti
on
s
O
il/
A
vo
ca
do
oi
l-e
nh
an
ce
d
di
et
P
U
FA
s,
ph
yt
os
te
ro
ls
,
an
d
ca
ro
te
no
id
s
N
ot
m
en
ti
on
ed
/p
.o
./
3
m
on
th
s
A
th
er
og
en
ic
-d
ie
t-
fe
d
ra
bb
it
s
↑H
D
L-
C
(K
ri
tc
he
vs
ky
et
al
.,
2
0
0
3
)
↓T
C
O
il/
A
vo
ca
do
oi
l-e
nh
an
ce
d
di
et
H
C
D
m
ic
e
↑H
D
L-
C
(O
rt
iz
M
or
en
o
et
al
.,
2
0
0
7
)
(C
on
ti
nu
es
)
AVOCADO AND METABOLIC SYNDROME
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
T
ab
le
3.
(C
on
ti
nu
ed
)
P
ar
t(
s)
of
th
e
pl
an
t
us
ed
/
Ex
tr
ac
t(
s)
A
ct
iv
e
co
ns
ti
tu
en
ts
D
os
ag
e
(m
g/
kg
/d
ay
)/
R
ou
te
/
du
ra
ti
on
of
tr
ea
tm
en
t
Ex
pe
ri
m
en
ta
lm
od
el
O
ut
co
m
e
R
ef
er
en
ce
M
U
FA
s,
ca
ro
te
no
id
s,
an
d
ph
yt
os
te
ro
ls
2
.5
%
or
5
%
(g
/1
0
0
g)
/p
.o
./
4
w
ee
ks
↓T
G
↓A
I
Fr
ui
ts
an
d
se
ed
s/
M
et
ha
no
lic
P
he
no
lic
s,
fl
av
on
oi
ds
,
an
d
so
lu
bl
e
di
et
ar
y
fi
be
r
1
0
%
,2
0
%
,3
0
%
/p
.o
./
6
w
ee
ks
H
C
D
ra
ts
↑A
I
(S
he
ha
ta
an
d
S
ol
ta
n,
2
0
1
3
)
↑G
S
H
↓T
C
,
T
G
,
an
d
LD
L-
C
↓A
S
T
an
d
A
LT
S
ee
ds
/m
et
ha
no
lic
an
d
pe
tr
ol
eu
m
et
he
r
S
ap
on
in
s,
fl
av
on
oi
ds
,
an
d
ph
en
ol
s
1
2
5
,
2
5
0
,
an
d
5
0
0
/p
.o
.
/4
w
ee
ks
H
FD
ra
ts
↓T
C
,
LD
L-
C
,
an
d
T
G
(M
fo
no
bo
ng
et
al
.,
2
0
1
3
)
↓T
ot
al
lip
id
s
an
d
P
Ls
↓A
I
P
ul
p/
H
yd
ro
al
co
ho
lic
To
co
ph
er
ol
s,
ph
yt
os
te
ro
ls
,
an
d
po
ly
ph
en
ol
s
1
3
0
an
d
1
5
0
/S
to
m
ac
h
tu
be
/
8
w
ee
ks
H
C
D
ra
ts
↑H
D
L-
C
(E
lb
ad
ra
w
y
an
d
S
he
lb
ay
a,
2
0
1
3
)
↓A
LT
an
d
A
S
T
↓U
re
a,
cr
ea
ti
ni
ne
,
ur
ic
ac
id
,
an
d
bi
lir
ub
in
↓S
er
um
ch
ol
es
te
ro
l,
T
G
,
LD
L-
C
,
an
d
V
LD
L-
C
P
ul
p/
N
ot
m
en
ti
on
ed
P
hy
to
st
er
ol
s,
M
U
FA
s,
ca
ro
te
no
id
s,
an
d
vi
ta
m
in
s
1
an
d
2
(m
L/
ra
t/
da
y)
/p
.o
./
1
0
w
ee
ks
H
C
D
ra
ts
↓S
er
um
ch
ol
es
te
ro
l,
LD
L-
C
,
V
LD
L-
C
,
an
d
T
G
(A
l-D
os
ar
i,
2
0
11
)
↓G
P
T,
G
O
T,
G
G
T,
an
d
A
LP
↓B
ili
ru
bi
n
le
ve
ls
↓L
iv
er
an
d
he
ar
t
M
D
A
S
ee
d
fl
ou
r/
M
et
ha
no
lic
P
he
no
lic
s
an
d
fi
be
r
1
2
5
,
2
5
0
,
an
d
5
0
0
/G
av
ag
e/
2
w
ee
ks
H
C
D
m
ic
e
↓T
C
an
d
LD
L-
C
(P
ah
ua
-R
am
os
et
al
.,
2
0
1
2
)
↓A
I
Fr
ui
t
an
d
le
av
es
/
D
ic
hl
or
om
et
ha
ni
c
an
d
m
et
ha
no
lic
N
ot
m
en
ti
on
ed
3
0
0
/p
.o
./
N
ot
m
en
ti
on
ed
T
yl
ox
ap
ol
-in
du
ce
d
hy
pe
rl
ip
id
em
ic
ra
ts
↓S
er
um
ch
ol
es
te
ro
l
(M
ah
ad
ev
a
R
ao
an
d
A
di
ne
w
,
2
0
11
)
↓T
G
S
ee
ds
/E
th
an
ol
ic
S
ap
on
in
s,
fl
av
on
oi
ds
,
an
d
ta
nn
in
s
1
0
,2
0
,
an
d
4
0
/p
.o
./
2
w
ee
ks
H
yp
er
lip
id
em
ic
ra
ts
↓T
C
,
T
G
,
an
d
LD
L-
C
(F
id
ri
an
ny
et
al
.,
2
0
1
6
)
Fr
ui
ts
/H
ex
an
e
ex
tr
ac
t,
ly
op
hi
liz
ed
,
an
d
po
w
de
re
d
av
oc
ad
o,
di
ff
er
en
t
fr
ac
ti
on
s
Fa
tt
y
ac
id
s
(A
vo
ca
do
in
di
et
=
1
–
5
%
),
(F
ra
ct
io
ns
=
4
.4
%
;
0
.5
3
%
;
0
.2
1
%
;
0
.9
8
%
;
an
d
1
.8
%
)/
p.
o.
/
2
w
ee
ks
D
-g
al
ac
to
sa
m
in
e-
in
du
ce
d
liv
er
da
m
ag
e
ra
ts
↓A
LT
an
d
A
S
T
(K
aw
ag
is
hi
et
al
.,
2
0
0
1
)
Le
av
es
/M
et
ha
no
lic
Fl
av
on
oi
ds
(lu
te
ol
in
,
ru
ti
n,
qu
er
ce
ti
n,
ap
ig
en
in
)
2
0
an
d
4
0
/p
.o
./
8
w
ee
ks
H
C
D
ra
ts
↑H
D
L-
C
(K
ol
aw
ol
e
et
al
.,
2
0
1
2
)
↓T
C
,
T
G
,
an
d
LD
L-
C
P
ul
p/
Et
ha
no
lic
S
ap
on
in
s,
fl
av
on
oi
ds
,
an
d
ph
yt
os
te
ro
ls
3
0
0
/p
.o
./
4
w
ee
ks
N
ep
hr
op
at
hy
-in
du
ce
d
H
C
D
ra
ts
↑S
O
D
an
d
C
A
T
(M
ah
ad
ev
a
R
ao
et
al
.,
2
0
1
4
)
↑G
P
x,
G
S
T,
G
R
,
an
d
G
S
H
↓T
C
an
d
T
G
↓S
er
um
ur
ea
,
cr
ea
ti
ni
ne
,
an
d
ur
ic
ac
id
↓T
B
A
R
S
an
d
hy
dr
op
er
ox
id
e
U
p-
re
gu
la
te
d
eN
O
S
ge
ne
s
(C
on
ti
nu
es
)
J. TABESHPOUR ET AL.
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
T
ab
le
3.
(C
on
ti
nu
ed
)
P
ar
t(
s)
of
th
e
pl
an
t
us
ed
/
Ex
tr
ac
t(
s)
A
ct
iv
e
co
ns
ti
tu
en
ts
D
os
ag
e
(m
g/
kg
/d
ay
)/
R
ou
te
/
du
ra
ti
on
of
tr
ea
tm
en
t
Ex
pe
ri
m
en
ta
lm
od
el
O
ut
co
m
e
R
ef
er
en
ce
D
ow
n-
re
gu
la
te
d
iN
O
S
ge
ne
s
S
ee
ds
/A
qu
eo
us
P
hy
to
st
er
ol
s
1
0
0
an
d
2
0
0
/p
.o
./
8
w
ee
ks
R
ab
bi
ts
↓T
C
,
T
G
,
LD
L-
C
,
an
d
to
ta
ll
ip
id
(N
w
ao
gu
ik
pe
an
d
B
ra
id
e,
2
0
11
)
Fr
ui
ts
/A
vo
ca
do
-e
nr
ic
he
d
di
et
P
he
no
lic
s
an
d
fl
av
on
oi
ds
5
,1
0
,
an
d
1
5
%
of
dr
ie
d
av
oc
ad
o/
p.
o.
/8
w
ee
ks
C
C
L 4
-in
du
ce
d
liv
er
da
m
ag
e
ra
ts
↑S
O
D
,
G
Px,
an
d
C
A
T
(M
ah
m
oe
d
an
d
R
ez
q,
2
0
1
3
)
P
ul
p/
A
vo
ca
do
-e
nr
ic
he
d
di
et
Fi
be
r
2
3
0
g
av
oc
ad
os
/p
.o
./
4
w
ee
ks
H
C
D
ra
ts
↑C
ec
um
w
ei
gh
t
(N
av
eh
et
al
.,
2
0
0
2
)
↓F
oo
d
co
ns
um
pt
io
n
↓B
od
y
w
ei
gh
t
ga
in
↓H
ep
at
ic
to
ta
lf
at
Fr
ui
ts
/H
yd
ro
al
co
ho
lic
M
U
FA
s
an
d
vi
ta
m
in
s
2
5
,5
0
,1
0
0
,
an
d
2
0
0
/p
.o
./
1
4
w
ee
ks
O
be
si
ty
-in
du
ce
d
H
FD
ra
ts
↑L
P
L
(M
on
ik
a
an
d
G
ee
th
a,
2
0
1
6
)
↓B
lo
od
an
d
liv
er
lip
id
s
↓L
P
O
↓F
A
S
N
↓H
M
G
C
oA
re
du
ct
as
e
Fr
ui
ts
/H
yd
ro
al
co
ho
lic
β-
si
to
st
er
ol
,
lu
te
in
,v
it
am
in
s
A
,
C
,
an
d
E
1
0
0
/p
.o
./
1
4
w
ee
ks
H
FD
ra
ts
↑G
S
H
(P
ad
m
an
ab
ha
n
an
d
A
ru
m
ug
am
,
2
0
1
4
)
↑A
di
po
ne
ct
in
an
d
m
R
N
A
ex
pr
es
si
on
of
ad
ip
on
ec
ti
n
↑P
PA
R
-γ
an
d
pr
ot
ei
n
ex
pr
es
si
on
of
P
PA
R
-γ
↓B
M
I,
T
FP
,
an
d
A
D
I
Le
av
es
/A
qu
eo
us
an
d
m
et
ha
no
lic
M
U
FA
s
1
0
/p
.o
./
8
w
ee
ks
H
FD
ra
ts
↓B
od
y
w
ei
gh
t
ga
in
(B
ra
ie
t
al
.,
2
0
0
7
a,
b)
↓L
iv
er
w
ei
gh
t
Fr
ui
ts
/h
yd
ro
al
co
ho
lic
Fl
av
on
oi
ds
,
ph
en
ol
ic
s,
an
d
ph
yt
os
te
ro
ls
1
0
0
/p
.o
./
1
4
w
ee
ks
H
FD
m
al
e
ra
ts
↑G
en
e
ex
pr
es
si
on
of
FG
F2
1
(M
on
ik
a
an
d
G
ee
th
a,
2
0
1
5
)
↓B
M
I,
T
FP
,
an
d
A
D
I
↓B
lo
od
ch
ol
es
te
ro
l,
T
G
,
an
d
LD
L-
C ↓L
ep
ti
n
↓m
R
N
A
ex
pr
es
si
on
of
FA
S
N
,
LP
L,
an
d
le
pt
in
Le
af
/A
qu
eo
us
an
d
m
et
ha
no
lic
Fl
av
on
oi
ds
1
0
/p
.o
./
8
w
ee
ks
H
FD
ra
ts
↑C
A
T,
S
O
D
,
an
d
G
S
H
(B
ra
ie
t
al
.,
2
0
1
2
)
↓P
ro
te
in
ca
rb
on
yl
↓P
la
sm
a
M
D
A
In
vi
tr
o
st
ud
ie
s
Le
av
es
an
d
fr
ui
t/
P
he
no
lic
P
he
no
lic
s
0
–
1
7
5
(μ
g/
m
L)
/N
ot
m
en
ti
on
ed
R
at
’s
pa
nc
re
as
m
od
el
↓M
D
A
(O
bo
h,
2
0
1
4
)
A
bb
re
vi
at
io
ns
.
M
U
FA
s,
m
on
ou
ns
at
ur
at
ed
fa
tt
y
ac
id
s;
p.
o.
,
or
al
ro
ut
e;
H
D
L-
C
,
hi
gh
-d
en
si
ty
lip
op
ro
te
in
ch
ol
es
te
ro
l;
A
po
-A
1
,
ap
ol
ip
op
ro
te
in
A
1
;
T
C
,
to
ta
l
ch
ol
es
te
ro
l;
LD
L-
C
,
lo
w
-d
en
si
ty
lip
op
ro
te
in
ch
ol
es
te
ro
l;
A
po
B
,
ap
ol
ip
op
ro
te
in
B
;
T
G
,
tr
ig
ly
ce
ri
de
;
H
C
D
,
hi
gh
-c
ho
le
st
er
ol
di
et
;
P
Ls
,
ph
os
ph
ol
ip
id
s;
B
M
I,
bo
dy
m
as
s
in
de
x;
A
S
T,
as
pa
rt
at
e
tr
an
sa
m
in
as
e;
A
LT
,
al
an
in
e
tr
an
sa
m
in
as
e;
A
ID
,
al
lo
xa
n-
in
du
ce
d
di
ab
et
ic
;
V
LD
L,
ve
ry
-lo
w
-d
en
si
ty
lip
op
ro
te
in
;
P
U
FA
s,
po
ly
un
sa
tu
ra
te
d
fa
tt
y
ac
id
s;
A
I,
at
he
ro
ge
ni
c
in
de
x;
H
FD
,
hi
gh
-f
at
di
et
;
G
P
T,
gl
ut
am
ic
py
ru
vi
c
tr
an
sa
m
in
as
e;
G
O
T,
gl
ut
am
ic
ox
al
oa
ce
ti
c
tr
an
sa
m
in
as
e;
G
G
T,
γ-
gl
ut
am
yl
tr
an
sp
ep
ti
da
se
;
A
LP
,
al
ka
lin
e
ph
os
ph
at
as
e;
M
D
A
,
m
al
on
di
al
de
hy
de
;
S
O
D
,
su
pe
ro
xi
de
di
sm
ut
as
e;
C
A
T,
ca
ta
la
se
;
G
P
x,
gl
ut
at
hi
on
e
pe
ro
xi
da
se
;
G
S
T,
gl
ut
at
hi
on
e
s-
tr
an
sf
er
as
e;
G
R
,
gl
ut
at
hi
on
e
re
du
ct
as
e;
T
B
A
R
S
,
th
io
ba
rb
it
ur
ic
ac
id
re
ac
ti
ve
su
bs
ta
nc
es
;
eN
O
S
,
en
do
th
el
ia
l
ni
tr
ic
ox
id
e
sy
nt
ha
se
;
iN
O
S
,
in
du
ci
bl
e
ni
tr
ic
ox
id
e
sy
nt
ha
se
;
C
C
L 4
,
ca
rb
on
te
tr
ac
hl
or
id
e;
LP
L,
lip
op
ro
te
in
lip
as
e
ac
ti
vi
ty
;
LP
O
,
lip
id
pe
ro
xi
de
s;
FA
S
N
,
fa
tt
y
ac
id
sy
nt
ha
se
;
P
PA
R
-γ
,
pe
ro
xi
so
m
e
pr
ol
if
er
at
or
-a
ct
iv
at
ed
re
ce
pt
or
-γ
;
FG
F2
1
,
fi
br
ob
la
st
gr
ow
th
fa
ct
or
-2
1
;
T
FP
,
to
ta
l
fa
t
pa
d
m
as
s;
A
D
I,
ad
ip
os
it
y
in
de
x.
AVOCADO AND METABOLIC SYNDROME
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
Clinical studies
A randomized trial to evaluate the hypolipidemic effects
of avocado (between half and one and a half avocados
per day) was accomplished on 15 women lasting for
3 weeks. A decrease in TC, LDL-C, and apolipoprotein
B together with preservation of HDL-C and
apolipoprotein A-I was observed (Colquhoun et al.,
1992). Also, in a crossover design, eight phenotype IV
and eight phenotype II dyslipidemic patients were
examined for evaluation of the effect of avocado on
blood lipids. Patients received a rich-monounsaturated
fatty acids diet using the avocado as their major source
for 4 weeks in which 30% of the total calories were
consumed as fat and 75% of the total fat from avocado.
The results showed that the diet significantly decreased
TC and LDL-C levels in phenotype II. On phenotype
IV, the diet produced a mild decrease in TG levels while
HDL-C significantly increased on both phenotypes
(Carranza et al., 1995). Sixteen healthy volunteers were
evaluated for the effect of avocado on serum lipid levels.
The volunteers received a rich-monounsaturated fatty
acids diet using the avocado as their major source for
2 weeks in which 30% of the total calories were
consumed as fat and 75% of the total fat from avocado.
The results revealed that the diet lessened the serum
levels of TC, TG, and LDL-C while the level of HDL-
C increased. So, avocado can be used as an alternative
to treat hyperlipidemia (Alvizouri-Muñoz et al., 1992).
Thirty healthy normolipidemic volunteers and 37 mild
HCh patients received an avocado-enriched diet (2000
Kcal, lipids 53% MFA 49 g saturated/unsaturated ratio
0.54) for 1 week. Both subjects revealed a significant
decrease in serum TC, LDL-C, and TG, and increase
in HDL-C levels with avocado diet. So avocado
is recommended for the treatment of HCh and
hypertriglyceridemic patients (López Ledesma et al.,
1996). A prospective, transversal, and comparative
study was accomplished on 13 patients with phenotype
II dyslipidemia for 4 weeks. Their diet composed of
60% carbohydrates, 10% proteins, and 30% lipids,
75% of which was supplied by avocado. TG and
LDL-C decreased significantly. They concluded that
avocado addition to a vegetarian diet does not
correct hypercholesterolemia unless lower amounts of
carbohydrates and polyunsaturated fatty acids are used
(Carranza-Madrigal et al., 1997). The effect of avocado
on serum cholesterol was investigated on 16 male
patients who consumed 0.5–1.5 avocados per day for
8 weeks. Total cholesterol (ester form free form) and
serum phospholipids (PLs) significantly declined at the
endpoint (Grant, 1960). Furthermore, in a clinical
study it was shown that addition of avocado or avocado
oil to the vegetable-based diets of healthy volunteers
enhanced the absorption of lycopene, β-carotene,
α-carotene, and lutein. It is concluded that adding
avocado fruit to carotenoid-containing foods can
facilitate carotenoid absorption (Unlu et al., 2005), and
consequently aids to its lipid-lowering activity.
In a randomized, controlled, parallel study, 61
free-living and energy-restricted-diets volunteers were
administered with 200 g/day of avocado (for 6 weeks)
which substituted for 30 g of other mixed dietary fats
such as margarine or oil, to investigate the possible
effects on weight loss, serum lipids, fibrinogen, and
vascular function. Although the results showed a
significant increase in the percentage of plasma oleic
acid and a decrease in the percentage of myristic acid,
body mass, body mass index (BMI), and the percentage
of body fat, but TC, TG, LDL-C, HDL-C levels,
fibrinogen, BP, and arterial compliance were not
changed significantly in the experimental group. This
study concluded that intake of 200 g/day of avocado
within an energy-restricted diet does not cause weight
loss when substituted for 30 g of mixed dietary fat
(Pieterse et al., 2005).
In vivo studies
The effect of reduced-calorie avocado paste (2 g/kg/day,
for 7 weeks) has been studied on HCD and high-
fructose diet rats. It showed a significant reduction in
TC, LDL-C, TG, AST, and ALT, and increased insulin
sensitivity (Pahua-Ramos et al., 2014). The results of a
study on AID rats suggested that ethanolic extracts of
P. americana seedpossess antihyperlipidemic effect at
the doses of 450 and 900 mg/kg via a significant decrease
in the serum concentrations of TC, TG, and LDL-C, in
addition to a significant increase in the serum level of
HDL-C. The possible mechanism of this effect was
mentioned to be controlling of the hydrolysis of certain
lipoproteins and their selective uptake and metabolism
by different tissues (Edem, 2010). Avocado-seed oil
(10% w/w, orally for 4 weeks) showed a significant
reduction in total liver lipogenesis, PL, and TG
synthesis, and protein content of plasma very-
low-density lipoprotein (VLDL) and HDL-C fractions
in female rats. The possible mechanism for the
alternations in hepatic lipogenesis could be related to
the marked proliferation of the smooth endoplasmic
reticulum which is known to be associated with
induction of enzymes involved in lipid biosynthesis
(Werman et al., 1991). The hypolipidemic and
antiatherogenic effects of avocado oil were investigated
in atherogenic-diet-fed rabbits. In this study, corn oil,
coconut oil, olive oil, and avocado oil were compared
for these effects. The results showed that the avocado
oil, corn oil, and olive oil had the same effects.
But, the atheroma observed in the rabbits fed avocado
oil was somewhat less severe than other oils
(Kritchevsky et al., 2003). The hypolipidemic and
antiatherogenic effects of avocado oil were evaluated
on hypercholesterolemic-diet mice (2.5 or 5% g/100 g,
for 4 weeks) and an increase in the HDL-C and
maintenance in the concentration of the TG, in spite of
the high caloric supply, was observed (Ortiz Moreno
et al., 2007).
The lowering effect of avocado seed on lipid profiles
in serum and liver was investigated in high-fat diet
(HFD) rats for 6 weeks. The results showed that
both the fruit and the seed, especially the latter,
significantly decreased the serum levels of TC, TG,
LDL-C, AST, and ALT activities, while the atherogenic
index (=Serum TC � HDL-C/HDL-C) increased.
Furthermore, in the liver, the contents of TC and
TG decreased, and GSH increased. Consequently,
consuming avocado seed is recommended because it
has strong antioxidant activity and improved lipid
profile (Shehata and Soltan, 2013). Petroleum ether
extracts of P. americana seeds were examined on HFD
rats. The extracts (125, 250, and 500 mg/kg/day, orally
J. TABESHPOUR ET AL.
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
for 4 weeks) significantly reduced the raised levels of
TC, LDL-C, TG, total lipids, total PLs, and the AI,
while increased HDL-C (Mfonobong et al., 2013). The
results of a study on hydroalcoholic extract of avocado
(130 and 150 mg/kg, via stomach tube for 8 weeks) on
HCD rats showed a significant reduction in serum
ALT, AST, urea, creatinine, uric acid, and bilirubin
levels. Also, significant decreases in serum cholesterol,
TG, LDL-C, and VLDL-C were noted, while, the serum
level of HDL-C enhanced (Elbadrawy and Shelbaya,
2013). P. americana pulp (1 and 2 mL/rat/day, orally
for 10 weeks) showed a significant decrease in serum
cholesterol, LDL-C, VLDL-C, TG, glutamic pyruvic
transaminase, glutamic oxaloacetic transaminase, γ-
glutamyl transpeptidase, alkaline phosphatase (ALP),
bilirubin levels, liver, and heart MDA. There was also
a significant increase in non-protein sulfhydryl and TP
contents in both tissues. These results suggested that
avocado showed hypocholesterolemic and antioxidant
properties because of its phytoconstituents contents
(Al-Dosari, 2011). Avocado seed flour (125, 250, and
500 mg/kg/day, by gavage, for 2 weeks) was
administered to HCD mice. The results showed a
significant reduction in the levels of TC, LDL-C, and
AI, suggesting the antioxidant and hypocholesterolemic
activity of this plant (Pahua-Ramos et al., 2012).
The cholesterol-lowering activity of leaf
(dichloromethanic and methanolic extracts) and fruit
(dichloromethanic and methanolic extracts) of P.
americana in tyloxapol-induced hyperlipidemic rats
were investigated [tyloxapol is used in Intraperitoneal
route injections to block plasma lipolytic activity, and
thus the breakdown of TG-rich lipoproteins]. The
results showed that the extracts (300 mg/kg, orally and
immediately after tyloxapol injection) could lower
cholesterol and TG levels in hyperlipidemic rats
(Mahadeva Rao and Adinew, 2011). The ethanolic seed
extract of P. americana (10, 20, and 40 mg/kg/day, orally
for 2 weeks) was administered to hyperlipidemic male
Wistar rats. The results showed that the extract at the
dose of 10 mg/kg reduced TC and LDL-C and at the
dose of 20 and 40 mg/kg reduced TG levels in serum.
This study showed that avocado can be served as a
potential medicinal plant to lower serum lipid levels
and subsequently the risk of CVDs (Fidrianny et al.,
2016). A rat model of D-galactosamine-induced liver
damage was conducted to assess the protective effects
of 22 fruits against liver injury (four experiments with
lyophilized and powdered avocado, its different
fractions and hexane extract) for 2 weeks. Among
different fruits, avocado showed extraordinarily potent
liver injury suppressing effect, dose dependently
(Kawagishi et al., 2001). The leaf extract of P. americana
(20 and 40 mg/kg/day for 8 weeks) was administered
to HCD rats. The results indicated that this extract,
in a dose-dependent manner, significantly reduced
the plasma levels of TC, TG, and LDL-C and
increased HDL-C levels. The extracts also caused
significant reduction of plasma lipid peroxidation.
In this study, the antihyperlipidemic effect of
avocado was comparable with that of cholestyramine
(Kolawole et al., 2012). The effects of avocado pulp
(300 mg/kg/day, orally for 4 weeks) on biochemical,
histological, and gene expression were investigated in
hypercholesterolemic-diet-fed nephropathy induced
albino rats. Via administration of the extract, the levels
of TC, TG, PLs, renal markers (serum urea, creatinine,
and uric acid), and renal lipid peroxidation products
such as thiobarbituric acid reactive substances and
hydroperoxide noticeably decreased. Also, free radical
scavenging activity factors such as superoxide dismutase
(SOD), catalase (CAT), glutathione peroxidase (GPx),
glutathione s-transferase, and glutathione reductase
(GR) enzymes were significantly increased. The mRNA
levels of endothelial nitric oxide synthase and inducible
nitric oxide synthase genes were meaningfully up-
regulated and down-regulated, respectively. This
study demonstrated that avocado could be used as a
nephroprotective agent via reducing the serum lipid
profile, renal oxidative stress, and regulating the
mRNA expression of NOS in renal artery (Mahadeva
Rao et al., 2014).
The aqueous seed extract of P. americana, at doses of
100 and 200 mg/kg/day for 2 months, was administered
to rabbits. The extract significantly and dose-
dependently showed reduction in TC, TG, LDL-C,
and the total lipid levels in the serum. Accordingly,
the seed of this plant could be a promising remedy for
the management of atherosclerosis, hypertension,
hyperlipidemia, hypercholesterolemia, and other
abnormalities of lipid metabolism in humans
(Nwaoguikpe and Braide, 2011). To assess the
hepatoprotective effect of avocado fruit, a rat model
experimental study was accomplished in carbon
tetrachloride-induced liver damage rats which received
diets consist of 5, 10, and 15% dried avocado fruits for
4 weeks. The results showed that avocado decreased
serum concentrations of AST, ALT, ALP, TP, total and
direct bilirubin, and MDA while significantly increased
the activity of SOD, GPx, and CAT enzymes.
Accordingly, avocado fruit improved liver functions
and showed antioxidant activity (Mahmoed and Rezq,
2013). Avocado also revealed its lipid-lowering effect
via influencing on endogenous fat synthesis and
adiponectin formation through the transcription factor
fibroblast growth factor-21 (Monika and Geetha,
2015). The leaf aqueous and methanolic extracts of P.
americana (10 mg/kg, for 8 weeks) were administered
to HCh rats. A significant reduction in proteincarbonyl
and plasma MDA showed that the extract lowered the
oxidative stress. Besides, an increase in the activities of
CAT and SOD as well as reduced GSH was observed.
The aforementioned effects demonstrated that the
extract could be used in the management of diseases
associated with hyperlipidemia (Brai et al., 2012).
Conversely, in a study, the effect of dietary
consumption of avocado oil was conducted on sucrose-
fed rats. No changes in biochemical markers including
glucose, TC, TG, total protein, albumin, globulin, direct
bilirubin, glutamic pyruvic transaminase, glutamic
oxaloacetic transaminase, ALP, cholinesterase, and
α-amylase were found while body weight gain was
observed in the rats (Carvajal-Zarrabal et al., 2014b).
In vitro studies
The inhibitory effect of the phenolic extract of the
leaves, seed, and fruit of P. americana (0–175 μg/mL)
on Fe2+-induced lipid peroxidation in rat’s pancreas
was examined in vitro. The results showed a significant
decrease in the MDA level in a dose-dependent
AVOCADO AND METABOLIC SYNDROME
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
manner. The seed extract have the highest inhibitory
effect. The possible mechanism is probably via the
ability of the extracts on chelating Fe2+ and scavenging
free radicals (Oboh, 2014).
Aforementioned experimental studies showed that
avocado had promising effects on abnormal lipid profile
via different mechanisms including increase in free
radical scavenging activity factors such as SOD, CAT,
GPx, glutathione s-transferase, and GR enzymes;
improving serum lipid biomarkers such as TC, TG,
LDL-C, and HDL-C; regulating the hydrolysis of
different lipoproteins and their selective uptake and
metabolism by different tissues; decrease in liver
lipogenesis and oxidative stress.
EFFECT ON OBESITY
Obesity which is associated with dyslipidemia, is a
critical global issue described by additional fat content
in adipose tissue as a result of unhealthy dietary habits
causing negative energy balance (Monika and Geetha,
2016; Colquhoun et al., 1992). According to the
McKinsey Global Institute report, more than 2.1 billion
people (nearly 30% of the world population) are
overweight or obese. It is estimated that by 2030 it will
rise to 41% (Carranza et al., 1995). Several methods
are available to prevent obesity such as working out,
applying medication, and modifying the regimen along
with avocado which has shown promising anti-obesity
effect in different studies.
Clinical studies
In a randomized, crossover, controlled feeding trial,
performed on 45 overweight or obese participants, the
hypolipidemic effect and also the effect of avocado
consumption (136 g of Hass avocado per day) on CVD
risk factors were investigated. The results indicated that
avocado significantly decreased LDL particle number,
small dense LDL-C, and the ratio of LDL/HDL from
baseline, and showed beneficial effects on cardio-
metabolic risk factors (Carranza et al., 1995). A
controlled parallel intervention study was accomplished
on overweight and obese volunteers with BMI of
27–44 kg/m2, to evaluate the effect of avocado (one
avocado/day for 6 weeks) on weight loss and serum
lipids. Significant reductions in body weight, BMI, and
percentage of body fat were observed (Unlu et al.,
2005).
In vivo studies
The effect of avocado pulp (230 g avocado) on body
weight was investigated in HCD rats for 4 weeks. The
results showed that food consumption, body weight
gain, and hepatic total fat levels were lower while the
cecum weight was higher in avocado-fed rats. In this
study, it was concluded that an appetite depressant is
present in avocado and that avocado pulp interferes
with hepatic fat metabolism (Monika and Geetha,
2015). The hypolipidemic and body weight-lowering
effects of hydroalcoholic fruit extract of P. americana
(25, 50, 100, and 200 mg/kg) on obesity-induced HFD
rats were investigated for 14 weeks. The experiment
showed a significant decrease in blood and liver lipids,
LPO, the activity of lipid metabolic key enzymes
such as fatty acid synthase (FASN) and HMG CoA
reductase in liver, while the antioxidant status and
lipoprotein lipase (LPL) activity increased. The possible
mechanism was probably via modulating the activities of
FASN and HMG CoA reductase in the liver (Monika
and Geetha, 2016).
For us to examine the hypolipidemic and anti-obesity
effects of hydroalcoholic fruit extract of P. americana,
HFD rats were administered with the dose of
100 mg/kg/day of the extract orally for 14 weeks. The
results revealed a significant decrease in BMI, total
fat pad mass (TFP), and adiposity index (ADI).
Although, an increase was observed in the levels of
GSH, adiponectin, mRNA expression of adiponectin,
peroxisome proliferator-activated receptor-γ (PPAR-γ),
and protein expression of PPAR-γ. Finally, it is
concluded that avocado possesses hypolipidemic and
anti-obesity activity probably via increasing the mRNA
expression of adiponectin and PPAR-γ, which can
reduce the risk of hyperlipidemia and obesity
(Padmanabhan and Arumugam, 2014). The effect of
aqueous and methanolic leaf extracts of P. americana
(10 mg/kg/day) on body weight and liver lipids in
HCD rats were investigated for 8 weeks, resulting in
14% and 25% reduction in the body weight gain,
respectively. The methanolic extract also provoked a
minimal (8%) reduction in mean liver weight. It could
be concluded that the leaf extract of avocado increased
catabolism of lipids accumulated in adipose tissue
causing a reduction in body weight but did not influence
liver lipid levels in rats (Brai et al., 2012). High-fat diet
rats were treated with 100 mg/kg of hydroalcoholic fruit
extract of avocado for 16 weeks. There was a significant
reduction in BMI, ADI, TFP, blood cholesterol, TG,
LDL-C, and leptin as well as the mRNA expression of
FASN, LPL, and leptin in subcutaneous and visceral
adipose tissue while the gene expression of fibroblast
growth factor-21 significantly increased. The current
study concluded that the anti-obesity effect of avocado
was due to its significant effect on leptin activity which
is responsible for satiety and hunger to control the food
intake (Monika and Geetha, 2015).
Several studies have demonstrated the anti-obesity
effect of avocado via different proposed mechanisms
such as increase in the mRNA expression of adiponectin
and PPAR-γ; increase in catabolism of lipids
accumulated in adipose tissue; reduction in BMI, body
weight, ADI, TFP, blood cholesterol, TG, LDL-C, and
leptin as well as the mRNA expression of FASN, LPL,
and leptin in subcutaneous and visceral adipose tissue;
and diminution of oxidative stress.
EFFECT ON HIGH BLOOD PRESSURE
Hypertension is estimated to cause 7.5 million deaths,
about 12.8% of the total of all deaths, worldwide, and
is a major risk factor for coronary heart disease,
hemorrhagic stroke, ischemic, and premature deaths.
Furthermore, hypertension accompanies with some
complications including heart failure, peripheral
J. TABESHPOUR ET AL.
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
vascular disease, retinal hemorrhage, and renal and
visual impairments (Papathanasiou et al., 2015). This
pervasive disease is defined as an average systolic blood
pressure ≥ 140 mmHg or an average diastolic blood
pressure ≥ 90 mm (CDC, 2012). Although the
antihypertensive drugs such as thiazides, angiotensin
converting enzyme inhibitors, beta-blockers, and
calcium channel blockers reduce the risk of mortality,
stroke, coronary heart disease, and/or CVDs, but
adverse events and the complexity of such agents tend
to decrease treatment adherence. Therefore,
complementary and herbal medicines are gaining
increasing popularity among patients with the risk of
CVDs, and there is a need to explore the medicinal
plants having very low adverse effects for the treatment
of hypertension (Xiong et al., 2015). There are several
clinical and experimental studies which confirm the use
of avocado as a remedy for hypertension (Table 4).
Clinicalstudies
For us to assess the effect of liquid extract of avocado
leaf on the plasma levels of LDL-C, TC, ALT, and
AST, 50 newly-diagnosed hypertensive patients with
an abnormal increase in plasma cholesterol and BP
were treated with 60 mL/day of the extract. The results
revealed a significant reduction in the plasma levels of
LDL-C and TC, and increase in ALT and AST in the
subjects. It can be concluded that although this extract
can induce hepatotoxicity, but also it can be used in
the treatment of hypertension (Olaniyan, 2014).
In vivo studies
For is to investigate the hypotensive effect of aqueous
seed extract of P. americana, normotensive rats were
treated with 240, 260, 280 mg/kg/day of the extract.
Treatment of the rats for 10 days showed a significant
decrease in mean arterial blood pressure and heart
rate (HR) which were comparable with those of
acetylcholine (Anaka et al., 2009). Hypertensive rats
were treated with 200, 500, and 700 mg/kg of the
aqueous seed extract of P. americana for 4 weeks to
evaluate the effect of this plant on BP and lipid profile.
The extract at the dose of 500 mg/kg showed a
significant reduction in BP as well as TC, LDL-C, TG
levels in the plasma, kidney, liver, and heart. It can be
concluded that treatment with the dose of 500 mg/kg
of the seed extract of this plant not only lowers the BP
but also may produce a favorable lipid profile (Imafidon
and Amaechina, 2010). Methanolic and aqueous leaves
extracts of P. americana were administered to
normotensive rats (6.25, 12.5, 25 and 50 mg/kg, for
2 weeks). The intravenous route injection of the extracts
showed a significant reduction in mean arterial blood
pressure (Adeboye et al., 1999).
The antihypertensive effect of the aqueous extract
obtained from the mixture of fresh leaf of P. americana,
stems, and fresh leaf of Cymbopogon citratus, fruits of
Citrus medica and honey (50, 100, and 150 mg/kg/day
for 5 weeks) on ethanol-and sucrose-induced
hypertension in rats were evaluated. The extract caused
reduction in BP, HR, MDA, the levels of TC, LDL-C,
TG, AI, glucose, proteins, AST, ALT, creatinin,
potassium, sodium, and albumin, while the levels of
HDL-C, GSH, nitrites, and the activities of SOD and
CAT increased. It can be concluded that the extract
showed antihypertensive activity (Dzeufiet et al.,
2014). The BP response to angiotensin II and the fatty
acid composition of cardiac and renal membranes were
evaluated with avocado oil-enhanced diet (10% w/w
for 2 weeks) in rats. Avocado oil increased the oleic acid
content of the cardiac membrane while it decreased the
α-linolenic acid and increased the arachidonic acid
content of the kidney membrane. The results showed
that this diet was able to modify the fatty acid content
in the mentioned membranes in a tissue-specific
manner. The rise in renal arachidonic acid suggested
that diet content could be an important factor in
vascular responses, and the desired effects for the
cardiovascular system could not be ascribed to the
components of the oil and proposed that other active
constituents present in avocado fruit and leaves might
be involved (Salazar et al., 2005). The aqueous seed
extract of P. americana (200, 500, and 700 mg/kg/day,
for 4 weeks) were used to assess its antihypertensive
and antihepatotoxic effect. The results showed that the
extract significantly lowered the weight gain, BP, and
ALP activity at all dose levels. The levels of protein,
albumin, ALT, and AST showed no significant change.
Conclusively, avocado seeds could be used as an
antihypertensive agent and also showed antihepatotoxic
activity (Imafidon, 2010). The aqueous extract of
the leaves and seeds of P. americana (2 mL) was
investigated on the enzyme activities of blood and liver
of the rats. The results showed a significant decrease
and increase in the activities of ALP, ALT, AST, and
acid phosphatase in the liver and plasma of the rats,
respectively; which indicated a probable damage to the
hepatic cells and might be as a result of prolonged
usage (1, 2, 3, 4, and 5 days) of the extract. The
cholesterol levels also decreased which indicated the
hypocholesterolimic effect of avocado and it might be
helpful in the management of hypertension and
reducing the risk of CVDs (Oyeyemi and Oyeyemi,
2015).
In vitro studies
The antioxidant activity of ripe and unripe avocado was
investigated via analysis of the minerals content using l,
l-diphenyl, 2-picrylhydrazyl (DPPH), superoxide, and
hydrogen peroxide scavenging assays. The results
showed that the content of sodium, calcium, magnesium,
iron, and manganese was higher in ripe avocado seeds,
while the content of potassium and zinc were higher in
unripe avocado seeds. It could be perceived that firstly,
the seeds from both ripe and unripe avocado contained
significant antioxidant activities; secondly, the seeds
from unripe avocado, being rich in potassium compared
to sodium, could be used in the management of
hypertension (Alagbaoso et al., 2015). The aqueous
extract of leaves and seeds of avocado (50 μL) were
used to investigate for their possible inhibitory effect
on angiotensin 1 converting enzyme (A1CE) activity
in vitro. The results showed that the leaf extract have
significantly higher total phenol, flavonoid content,
and antioxidant properties than the seed extract, while,
the seed extract have higher inhibitory effect on A1CE
AVOCADO AND METABOLIC SYNDROME
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
Ta
bl
e
4.
H
yp
ot
en
si
ve
ef
fe
ct
s
of
av
oc
ad
o
C
lin
ic
al
tr
ia
ls
Le
av
es
/L
iq
ui
d
A
lk
al
oi
ds
6
0
(m
L/
da
y)
/p
.o
./
N
ot
m
en
ti
on
ed
N
ew
ly
di
ag
no
se
d
hy
pe
rt
en
si
ve
pa
ti
en
ts
↑A
LT
an
d
A
S
T
(O
la
ni
ya
n,
2
0
1
4
)
↓T
C
an
d
LD
L-
C
A
ni
m
al
st
ud
ie
s
S
ee
d/
A
qu
eo
us
Ta
nn
in
s
2
4
0
,2
6
0
,
an
d
2
8
0
/i.
v.
/1
0
da
ys
N
or
m
ot
en
si
ve
ra
ts
↓M
A
B
P
(A
na
ka
et
al
.,
2
0
0
9
)
↓H
R
S
ee
d/
A
qu
eo
us
P
ot
as
si
um
M
U
FA
s,
ca
ro
te
no
id
s,
an
d
β-
si
to
st
er
ol
2
0
0
,5
0
0
,
an
d
7
0
0
/i.
v.
/4
w
ee
ks
H
yp
er
te
ns
iv
e
ra
ts
↓B
P
(I
m
af
id
on
an
d
A
m
ae
ch
in
a,
2
0
1
0
)
↓T
C
,
T
G
,
an
d
LD
L-
C
Le
av
es
/A
qu
eo
us
an
d
m
et
ha
no
lic
A
lk
al
oi
ds
,
sa
po
ni
ns
,
fl
av
on
oi
ds
,
an
d
ta
nn
in
s
6
.2
5
,1
2
.5
,2
5
,
an
d
5
0
/i.
v.
/
2
w
ee
ks
N
or
m
ot
en
si
ve
ra
ts
↓M
A
B
P
(A
de
bo
ye
et
al
.,
1
9
9
9
)
Le
av
es
/A
qu
eo
us
Fl
av
on
oi
ds
,
sa
po
ni
ns
,
ta
nn
in
s,
po
ly
ph
en
ol
s,
an
d
al
ka
lo
id
s
5
0
,1
0
0
,
an
d
1
5
0
/p
.o
./
5
w
ee
ks
Et
ha
no
l-a
nd
su
cr
os
e-
in
du
ce
d
hy
pe
rt
en
si
ve
ra
ts
↑H
D
L-
C
(D
ze
uf
ie
t
et
al
.,
2
0
1
4
)
↑G
S
H
,
ni
tr
it
es
,
S
O
D
,
an
d
C
A
T
↓B
P
an
d
H
R
↓M
D
A
↓T
C
,
LD
L-
C
,
an
d
T
G
↓A
I
↓G
lu
co
se
an
d
pr
ot
ei
ns
↓A
S
T
an
d
A
LT
↓C
re
at
in
in
,
po
ta
ss
iu
m
,
so
di
um
,
an
d
al
bu
m
in
O
il/
A
vo
ca
do
oi
l-e
nh
an
ce
d
di
et
N
ot
m
en
ti
on
ed
1
0
%
(w
/w
)/
p.
o.
/2
w
ee
ks
M
al
e
ra
ts
↑C
ar
di
ac
ol
ei
c
ac
id
(S
al
az
ar
et
al
.,
2
0
0
5
)
↑K
id
ne
y
ar
ac
hi
do
ni
c
ac
id
↓K
id
ne
y
α-
lin
ol
en
ic
ac
id
S
ee
ds
/A
qu
eo
us
N
ot
m
en
ti
on
ed
2
0
0
,5
0
0
,
an
d
7
0
0
/p
.o
./
4
w
ee
ks
H
yp
er
te
ns
iv
e
an
d
no
rm
ot
en
si
ve
ra
ts
↓W
ei
gh
t
ga
in
(I
m
af
id
on
,
2
0
1
0
)
↓B
P
↓ A
LP
Le
av
es
an
d
se
ed
s/
A
qu
eo
us
N
ot
m
en
ti
on
ed
2
m
L/
p.
o.
/5
da
ys
R
at
s
P
la
sm
a:
↑A
LP
,
A
LT
,
A
S
T,
an
d
A
C
P
(O
ye
ye
m
ia
nd
O
ye
ye
m
i,
2
0
1
5
)
Li
ve
r:
↓A
LP
,
A
LT
,
A
S
T,
an
d
A
C
P
In
vi
tr
o
st
ud
ie
s
S
ee
ds
/N
ot
m
en
ti
on
ed
P
ot
as
si
um
an
d
ph
en
ol
ic
s
N
ot
m
en
ti
on
ed
/N
ot
m
en
ti
on
ed
D
P
P
H
,
su
pe
ro
xi
de
,
an
d
hy
dr
og
en
pe
ro
xi
de
sc
av
en
gi
ng
as
sa
ys
↓B
P
(A
la
gb
ao
so
et
al
.,
2
0
1
5
)
Le
av
es
an
d
se
ed
s/
A
qu
eo
us
P
he
no
lic
s
an
d
fl
av
on
oi
d
5
μL
/N
ot
m
en
ti
on
ed
S
pe
ct
roph
ot
om
et
er
y
In
hi
bi
ti
on
of
A
1
C
E
(O
du
ba
nj
o
et
al
.,
2
0
1
6
)
A
1
C
E
in
hi
bi
ti
on
as
sa
y
Le
av
es
/A
qu
eo
us
N
ot
m
en
ti
on
ed
0
.0
1
–
1
2
.8
(m
g/
m
L)
/N
ot
m
en
ti
on
ed
Is
ol
at
ed
ra
t
ao
rt
a
In
hi
bi
ti
on
of
C
a2
+
in
fl
ux
th
ro
ug
h
ca
lc
iu
m
an
d
re
ce
pt
or
-o
pe
ra
te
d
ch
an
ne
ls
(O
w
ol
ab
ie
t
al
.,
2
0
0
5
)
A
bb
re
vi
at
io
ns
.
p.
o.
,
or
al
ro
ut
e;
A
LT
,
al
an
in
e
tr
an
sa
m
in
as
e;
A
S
T,
as
pa
rt
at
e
tr
an
sa
m
in
as
e;
T
C
,
to
ta
lc
ho
le
st
er
ol
;
LD
L-
C
,
lo
w
-d
en
si
ty
lip
op
ro
te
in
ch
ol
es
te
ro
l;
i.v
.,
in
tr
av
en
ou
s
ro
ut
e;
M
A
B
P,
m
ea
n
ar
te
ri
al
bl
oo
d
pr
es
su
re
;
H
R
,
he
ar
t
ra
te
;
M
U
FA
s,
m
on
ou
ns
at
ur
at
ed
fa
tt
y
ac
id
s;
B
P,
bl
oo
d
pr
es
su
re
;
T
G
,
tr
ig
ly
ce
ri
de
;
H
D
L-
C
,
hi
gh
-d
en
si
ty
lip
op
ro
te
in
ch
ol
es
te
ro
l;
S
O
D
,
su
pe
ro
xi
de
di
sm
ut
as
e;
C
A
T,
ca
ta
la
se
;
M
D
A
,
m
al
on
di
al
de
hy
de
;
A
I,
at
he
ro
ge
ni
c
in
de
x;
A
LP
,
al
ka
lin
e
ph
os
ph
at
as
e;
A
C
P,
ac
id
ph
os
ph
at
as
e;
D
P
P
H
,
l;
l-d
ip
he
ny
l;
2
-p
ic
ry
lh
yd
ra
zy
l;
A
1
C
E,
an
gi
ot
en
si
n
1
co
nv
er
ti
ng
en
zy
m
e.
J. TABESHPOUR ET AL.
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
than the leaf extract. It could be concluded that the seed
indicated a better antihypertensive activity while the
leaf revealed a better antioxidant activity (Odubanjo
et al., 2016). The vasorelaxant effect of the aqueous
leaves extract of P. americana (0.01–12.8 mg/mL) was
examined on isolated rat aorta. The results indicated
that the extract showed a significant vasorelaxation in
a concentration-related manner, and the effect was
dependent on the synthesis or release of endothelium-
derived relaxing factors and the release of prostanoid.
This effect could also be probably due to inhibiting
Ca2+ influx through calcium channels and, to a lesser
extent, receptor-operated channels. It could be
concluded that mentioned vascular effects could explain
the hypotensive activity of the extract and its usage
in the treatment of hypertension (Owolabi et al., 2005).
The vasorelaxant effect of avocado has been
demonstrated to be via the synthesis or release of
endothelium-derived relaxing factors, the release of
prostanoid and inhibiting Ca2+ influx through calcium
channels.
EFFECT ON ATHEROSCLEROSIS
Clinical studies
Postprandial effect of 68 g addition of avocado to a
hamburger was evaluated on vasodilation and
inflammation of healthy volunteers. The
vasoconstriction following hamburger ingestion was
not observed when the avocado flesh was ingested
together with the burger. There was a significant
preservation of Ikappa-B alpha as an inflammatory
factor, consistent with reduced activation of the
NF-kappa B inflammatory pathway. Avocado also
decreased the elevated levels of TG. The results
suggested that avocado had beneficial anti-
inflammatory and vascular health effects when
co-ingested with a hamburger patty (Li et al., 2013).
In vivo studies
Cardiovascular risk profile markers were evaluated in a
rat model of sucrose-indused methabolic changes,
treated with avocado oil. The oil reduced TG, VLDL,
and LDL (significant) levels while no change was
observed in HDL levels. It also reduced the
concentration of high sensitivity C-reactive protein
which is an indicator of inflammatory processes. The
results of this study showed that avocado oil
consumption reduced inflammatory processes and via
improving these biomarkers, could prevent the
development of MetS (Carvajal-Zarrabal et al., 2014a).
The cardiovascular effects of P. americana aqueous leaf
extract were investigated in three different animal
models. In the first experiment, the effect of the extract
on myocardial contractile performance was assessed on
guinea pig isolated atrial muscle strips. In the second
experiment, the vasodilatory effects of the extract were
assessed on isolated portal veins and thoracic aortic
rings of healthy rats in vitro. In the third experiment,
the hypotensive effect of the extract was assessed in
healthy normotensive and hypertensive rats in vivo.
The results indicated that the extract caused
bradycardia, vasorelaxation, and hypotension in these
animal models, which encouraged the use of avocado
in management of essential hypertension and certain
cases of cardiac dysfunctions (Ojewole et al., 2007).
The effect of methanolic seed extracts of P. americana
(200, 400, 800, and 1600 mg/kg/day for 4 weeks) on
prothrombin time (PT) and activated partial
thromboplastin time (APTT) tests was evaluated in
mice. The results showed that the increase in PT and
APTTwas dose dependent. Because the extract showed
anticoagulant activity as it prolonged PT and APTT, it
could be used as a cardio protective agent (EE et al.,
2015). The antiplatelet and antithrombotic activities of
avocado pulp were investigated both in vitro and
in vivo. The results showed that antiplatelet activity
was initially attributed to Persenone-C (the most potent
antiplatelet acetogenin) and Persenone-A (in vitro).
The latter showed protective effects against arterial
thrombosis (25 mg/kg, in vivo) as increased coagulation
times and decreased thrombus formation. Inhibition of
platelet aggregation may be due to the existence of
acetogenin compounds in avocado. These compounds
showed potential preventive effect on thrombus
formation and were effective in ischaemic diseases
(Rodriguez-Sanchez et al., 2015). Avocado fruit extracts
were examined for their phytochemical, toxicological,
biochemical, and hematological properties in rats.
Extract treatment caused reduction of the activity of
liver and heart enzymes including TC, VLDL, LDL,
while HDL levels increased PT and APTT with kaolin
also decreased. It could be concluded that the extract
acted as a potential inhibitor of CVDs because of its
preventive and possible curative values. Its role in the
regulation of blood clotting time may be because of
its significant vitamin K content (Gouegni and
Abubakar, 2013).
ANTIOXIDANT ACTIVITY
Different parts of avocado such as leaves, pulp, seeds,
peels, roots, and plant derived products are proved to
have significant health benefits in different components
of MetS because of their antioxidant activity, which can
neutralize the oxidative stress, and cellular oxidation
reaction under appropriate conditions (Abdulazeez
and Ponnusamy, 2016; Wang et al., 2016). Promising
observations have been made on the andioxidant
activity of avocado and its antidiabetic effect via
different mechanisms such as inhibition of α-amylase
and α-glucosidase (Ajani and Olanrewaju, 2014). Also
the hypolipidemic effect of avocado has been
demonstrated to be through its antioxidant activity
because of its high carotenoid content (Unlu et al.,
2005). The hypotensive effect of avocado and its
antioxidant activity has been proved via the
improvement of biochemical and oxidative status, and
via protecting liver, kidney, and vascular endothelium
against oxidative stress parameters (Dzeufiet et al.,
2014). It is also believed that avocado in the diet
through its effects on lipid metabolism and antioxidant
properties, plays an important role in the prevention of
CVDs (Pieterse, 2003).
AVOCADO AND METABOLIC SYNDROME
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
For us to examine the antioxidant activity of the
solvent extracts of avocado seeds, four different
fractions were used to calculate this activity. All
fractions were able to scavenge DPPH among which
one fraction had antioxidant activity comparable with
ascorbic acid (Nagaraj et al., 2010). Furthermore, the
seeds, peels, and pulp of avocado were extracted with
acetone/water/acetic acid solvents to determine their
antioxidant capacity (1 g of pulp or 0.5 g of seeds or
peels were extracted in 10 mL of the solvents), total
phenolic content and to identify the major antioxidant
compounds. Among different parts, the seedsshowed
the highest antioxidant capacity. Procyanidins were
the major phenolic compounds that contributed to
antioxidant capacity. This study suggested that avocado
seeds and peels could be used as source of antioxidants
(Wang et al., 2010). The anticholinesterases and
antioxidant activities of P. americana leaf and seed
aqueous extracts were investigated via the activities
of acetylcholinesterase and butyrylcholinesterase
enzymes which are linked with Alzheimer disease, and
DPPH, hydroxyl and nitric oxide scavenging ability,
respectively. The leaf extract showed the highest
phenolic content and radical scavenging activity (Oboh
et al., 2016). Different phytoconstituents of the leaves of
P. americana were isolated, and their antioxidant
activity were evaluated using DPPH and H2O2 assays.
This study concluded that the leaves had antioxidant
activity which may be helpful in preventing the progress
of various oxidative stress related diseases (Owolabi
et al., 2010). Different phytoconstituents of the leaves
of P. americana were isolated and their antioxidant
activity were evaluated using DPPH, NO and reducing
power and radical scavenging activity assays. This study
concluded that methanolic extract of avocado
possessed significant antioxidant activity (Asaolu
et al., 2010). In a study, it was shown that avocado fruit
had great ascorbic acid, total phenol concentrations,
antioxidant capacity, and high levels of catalase,
ascorbate peroxidase, and GR activities (Wang et al.,
2016). The diethyl nitrosamine-induced elevated levels
of tumor necrosis factor-α, cyclooxygenase-2,
lipoxygenase, caspase-3, DNA fragmentation, NO,
MDA, TP, and serum lipid profile and liver functions
were corrected in rats treated with avocado extract
(1 mL/kg/day, orally for 4 weeks). The results indicated
that avocado was able to diminish oxidative stress,
inflammation, and apoptosis induced by diethyl
nitrosamine (Hamouda, 2015). In a study, the
antioxidant activity of avocado was shown in different
parts as follows: leaf > peel > oil > pulp, using DPPH
assay. The antioxidant activity showed a positive
correlation with total flavonoid content, and these parts
were useful for future antioxidant products (Kumar and
Cumbal, 2016).
SAFETY
The safety of avocado has been demonstrated in a study
in which 2.5 g/kg (p.o) per day of the aqueous seed
extract of P. americana, in a sub-acute experiment, were
administered to the rats for 4 weeks. The extract did not
affect the whole body weight or organ-to-body weight
ratios though significantly increased the fluid intake
and the concentration of total proteins. It could be
concluded that this extract at the mentioned dose was
safe on sub-acute basis (Ozolua et al., 2009).
CONCLUSION
In this review, we summarized different in vivo, in vitro
and clinical studies accomplished by researchers around
the world to find out the role of peel, seed, flesh, and
leaves of avocado in MetS. Most of these studies have
suggested the use of this plant in the diet, on a daily
basis, to manage different components of MetS.
According to the experimental studies reported in the
literature, we observed that avocado had the most effect
on lipid profile. The most affected biomarkers were
LDL-C, HDL-C, TG, TC, and PLs. The reported
mechanism of this effect was regulating of the hydrolysis
of certain lipoproteins and their selective uptake and
metabolism by different tissues such as liver and
pancreas. Another possible mechanism could be related
to the marked proliferation of the liver smooth
endoplasmic reticulum which is known to be associated
with induction of enzymes involved in lipid biosynthesis.
In this review article, satisfactory clinical evidence
suggested that avocado can be used as herbal dietary
supplements for treatment of different components of
MetS. Although, avocado like other herbal products is
safe and generally better tolerated than synthetic
medications, there is limited scientific evidence to
evaluate different side effects because of contaminants,
or interactions with drugs. Besides, further studies need
to be accomplished on the metabolic effects of different
parts of avocado for other possible mechanisms.
Conflict of Interest
The authors declare not to have any conflicts of interest.
REFERENCES
Abdulazeez SS, Ponnusamy P. 2016. Antioxidant and
hypoglycemic activity of strawberry fruit extracts against
alloxan induced diabetes in rats. Pak J PharmSci29: 255–260.
Adeboye JO, Fajonyomi MO, Makinde JM, Taiwo OB. 1999. A
preliminary study on the hypotensive activity of Persea
americana leaf extracts in anaesthetized normotensive rats.
Fitoterapia 70: 15–20.
Ajani A, Olanrewaju BO. 2014. Avocado pear fruits and leaves
aqueous extracts inhibit α-amylase, α-glucosidase and snp
induced lipid peroxidation–an insight into mechanisms involve
in management of type 2 diabetes. Int J Appl Nat Sci 3: 21–34.
Akaberi M, Hosseinzadeh H. 2016. Grapes (Vitis vinifera) as a
potential candidate for the therapy of the metabolic syndrome.
Phytother Res 30: 540–556.
Al-Dosari MS. 2011. Hypolipidemic and antioxidant activities of
avocado fruit pulp on high cholesterol fed diet in rats. Afr J
Pharm Pharmacol 5: 1475–1483.
Alagbaoso CA, Tokunbo II, Osakwe OS. 2015. Comparative
study of antioxidant activity and mineral composition of
methanol extract of seeds of ripe and unripe avocado
pear (Persea americana, Mill.). NISEB Journal 15:
123–127.
J. TABESHPOUR ET AL.
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. (2017)
Alhassan A, Sule M, Atiku M,Wudil A, Abubakar H, Mohammed S.
2012. Effects of aqueous avocado pear (Persea americana)
seed extract on alloxan induced diabetes rats. Greener J Med
Sci 2: 5–11.
Alvizouri-Muñoz M, Carranza-Madrigal J, Herrera-Abarca JE,
Chávez-Carbajal F, Amezcua-Gastelum JL. 1992. Effects of
avocado as a source of monounsaturated fatty acids on
plasma lipid levels. Arch Med Res 23: 163–167.
Anaka ON, Ozolua RI, Okpo SO. 2009. Effect of the aqueous seed
extract of Persea americana Mill (Lauraceae) on the blood
pressure of Sprague-Dawley rats. Afr J Pharm Pharmacol 3:
485–490.
Antia B, Okokon J, Okon P. 2005. Hypoglycemic activity of
aqueous leaf extract of Persea americana Mill. Indian J
Pharmacol 37: 325–326.
Asaolu M, Asaolu S, Fakunle J, Emman-Okon B, Ajayi E, Togun R.
2010. Evaluation of in-vitro antioxidant activities of methanol
extracts of Persea americana and Cnidoscolus aconitifolius.
Pak J Nutr 9: 1074–1077.
Awad AB, Fink CS. 2000. Phytosterols as anticancer dietary
components: evidence and mechanism of action. J Nutr 130:
2127–2130.
Brahmachari G. 2011. Bio-flavonoids with promising antidiabetic
potentials: a critical survey. In Opportunity, Challenge and
Scope of Natural Products in Medicinal Chemistry, Tiwari VK,
Mishra BB (eds), 1st edn. Research Signpost: Trivandrum;
187–212.
Brai B, Odetola A, Agomo P. 2007a. Effects of Persea americana
leaf extracts on body weight and liver lipids in rats fed
hyperlipidaemic diet. Afr J Biotechnol 6: 1007–1011.
Brai BI, Odetola A, Agomo P. 2007b. Hypoglycemic and
hypocholesterolemic potential of Persea americana leaf
extracts. J Med Food 10: 356–360.
Brai BI, Odetola AA, Akindele SK, Fesobi TW, Agomo PU. 2012.
Evaluation of antiperoxidative and antioxidant properties of
aqueous and methanolic leaf extracts of Persea americana mill.
In rats fed high lipid diet. Can J Pure Appl Sci 6: 2079–2088.
Carranza-Madrigal J, Herrera-Abarca JE, Alvizouri-Muñoz M,
Alvarado-Jimenez MR, Chavez-Carbajal F. 1997. Effects of a
vegetarian diet vs. a vegetarian diet enriched with avocado in
hypercholesterolemic patients. Arch Med Res 28: 537–541.
Carranza J, Alvizouri M, Alvarado MR, Chávez F, Gómez M,
Herrera JE. 1995. Effects of avocado on the level of blood
lipids in patients with phenotype II and IV dyslipidemias. Arch
Inst Cardiol Mex 65: 342–348.
Carvajal-Zarrabal O, Nolasco-Hipolito C, Aguilar-Uscanga MG,
Melo-Santiesteban G, Hayward-Jones PM, Barradas-Dermitz
DM. 2014a. Avocado oil supplementation modifies
cardiovascular