An assessment of the health protective properties of artichoke – a

plant rich in bioactive compounds

Submitted: May 2015

Abstract:

Fruits and Vegetables are an important part of our diet as they have many positive effects as they
contain vitamins, minerals, flavonoids and polyphenols. The aim of the study is to appreciate the
information obtained about the artichoke, from a large research and support the statement that
artichoke contains healthy protective compounds. Artichoke can be considered one of the world’s
medical plants that can have manifold beneficial effects. Flavonoids and phenols are the two
categories of the bioactive compounds present in the artichoke that can offer the beneficial effects.
The major flavonoids present in the artichoke are luteolin and apigenin where caffeic acid and
dicaffeolquinic acids (chlorogenic acid and cynarin) belong to the phenolic family. Nowadays,
cardiovascular diseases serve as the world’s major cause of death and can be derived by bad eating
habits which lead to high blood cholesterol levels. Artichoke extract compounds have the ability to
reduce the plasma cholesterol levels. The LDL oxidation can be inhibited by the antioxidant activity
of flavones and phenols preventing the onset of cardiovascular diseases, while the strong anti-
cancer effects of the bioactive compounds can lead to cancer cell apoptosis. In many studies done
in vivo and in vitro, the components of the artichoke indicated that have antioxidant,
hepatoprotective and cardioprotective properties. This dissertation summarizes the action of phenols
1
and flavonoids present in the artichoke that give rise to different protective benefits. Based on the
results obtained after research, it is concluded that the often consumption of artichoke will lead to a
healthier life.

Keywords: artichoke, flavonoids, phenols, chlorogenic acid, luteolin, apigenin, caffeic acid,
Hepatoprotective, Cardioprotective, Cancer Cell apoptosis

(Word Count: 252 words)

1.0 Introduction

1.1 The artichoke

Artichoke is a vegetable from relatively small genus (Asteraecea) that is considered as an important
component of the Mediterranean diet. Is a vegetable rich in minerals, dietary fibre and low amount
of lipids. In addition to this, artichoke is full of polyphenol compounds that can show a nutritional,
pharmaceutical and protective properties to humans. Also, artichoke contains phenolic acids that
have a principal role in the human diet, as they are healthy to be consumed by humans.9

1.2 – Different types of artichoke

There are three types of artichoke which include globe artichoke, cardoon artichoke and Jerusalem
artichoke and they can be summarized in Table 1.1

2
 Globe artichoke
The globe artichoke contains a low content of fat and high levels
of minerals (potassium, sodium, phosphorus) as well as vitamin C,
fibres, polyphenols, flavones, inulin hydroxycinnamates
(caffeoylquinic acid derivatives) and luteolin glucosides. 1

Cardoon artichoke
The cardoon artichoke contains polyphenol compounds as well
such as caffeoylquinic derivatives. The chlorogenic acid is found
to have the highest concentration in it. The artichoke is one of the
oldest vegetables that have been cultivated

Jerusalem artichoke
Jerusalem artichoke is not an actual artichoke, but belongs to the
sunflower family but this a brown skinned tuber. It has nothing to
do with Jerusalem though, their name is derived from the Italian
name of sunflower, girasole. Jerusalem artichokes are available
and they are best from November to March. Their white flesh is
sweet, crunchy and is an excellent iron source. (2,3)
Table 1.1 – The three types of artichoke

1.3 – History and cultivation period

Artichokes are available 12 months a year and they have a peak season during spring and fall. There
is not enough information on the origin of the artichoke. It is believed that the wild cardoon was
originated during the Middle Ages in the Mediterranean (ranging from Cyprus to Portugal) by rich
and royal people, Arabs. This is because Arabs showed an interest in growing garden crops (Idrisi
2005).10 The globe artichoke though, it was thought that had Mediterranean basis as well, but
around North-Western Africa. It is assumed that, Sicily and Italy are the originated places (Pignone
and Sonnante 2004). Italy is considered as the first country in the production of globe artichoke
(470 000) and Spain follows (189,000). Other countries that have an increased in the production of
artichokes are Morocco, Grace, USA, China, Peru and Argentina.10

Some historians though, believe that artichoke was first cultivated by the ancient Greeks and
5,
Romans and this is because both of them mentioned their consumption. Ancient Greeks and
Romans, considered the artichoke as a digestive aid. Greeks support that the cardoon artichoke was
3
the first artichoke to be cultivated (thesis) and the artichoke is the improved version of that. Both
cardoon and globe artichokes were originated from the same plant due to the fact that they have
very similar characteristics. 5

Europeans use the leaves of the artichoke as diuretic in order to stimulate the bile production. As
studies have shown, the artichoke has a health, protective and hepatoprotective effect on humans. 5

1.4 - The genome of the Artichoke

The chloroplast genome of the artichoke is a diploid crop and is 152,529 bp long. It is consisted of
one LSC of 83,578 bp, one SSC of 18,641 and a pair of IRs of 25,155 bp each. This genome,
consists of 115 distinct genes and these can include 30 tRNA, 4rRNA and 80 protein coding genes.
Additionally, the artichoke genome includes photosystems I and II, cytochrome b6/f, ATP synthase,
rubisco, RNAP, proteins, ribosomal RNAS, transfer RNAS, and NADH oxidoreductase42.

1.5- The constituents of artichoke

Column1 Column2 Column3
Nutrient Unit 1Value per 100 g
Water g 84.94
Energy kcal 47
Protein g 3.27
Total lipid (fat) g 0.15
Carbohydrate, by difference g 10.51
Fiber, total dietary g 5.4
Sugars, total g 0.99
Minerals
Calcium, Ca mg 44
Iron, Fe mg 1.28
Magnesium, Mg mg 60
Phosphorus, P mg 90
Potassium, K mg 370
Sodium, Na mg 94
Zinc, Zn mg 0.49
Vitamins

4
 Vitamin C, total ascorbic acid mg 11.7
Thiamin mg 0.072
Riboflavin mg 0.066
Niacin mg 1.046
Vitamin B-6 mg 0.116
Folate, DFE µg 68
Vitamin B-12 µg 0
Vitamin A, RAE µg 1
Vitamin A, IU IU 13
Vitamin E (alpha-tocopherol) mg 0.19
Vitamin D (D2 + D3) µg 0
Vitamin D IU 0
Vitamin K (phylloquinone) µg 14.8
Lipids
Fatty acids, total saturated g 0.036
Fatty acids, total g 0.005
monounsaturated
Fatty acids, total g 0.064
polyunsaturated
Cholesterol mg 0
Table 1.2 – All the constituents in an artichoke per 100 g. Data obtained from USDA National
Nutrient data base 44.
Table 1.2 illustrates the different constituents of the artichokes. These can include phenols,
minerals, vitamins and electrolytes.

1.5.1 – Beneficial effects of the artichoke

The artichoke extract is used as an herbal medicine (Gebhart 2001). It is considered to have
phytopharmaceuticals and clinical effects that were evident by biomedical researches that will be
described below. Since ancient times, it was used to cure diseases including gastrointestinal,
metabolic and cardiovascular.7

1.5.2 – Phenolic acids

Cynara Codinculus L is a type of globe artichoke that is full of phenolic acids and flavonoids and
are considered as the most active compounds. The phenolic acids are comprised by two subgroups
such as hydroxybenzoic and hydroxycinnamic acids. Hydroxycinnamic acids includes chlorogenic
acid, coumaric, ferulic acids and caffeic acid derivatives which include cynarin, luteolin,
scolymoside and cynaroside. Cynarin was the first one that was isolated and was originally
considered as the most active compound into the artichoke. The chlorogenic acid is known as the

5
most powerful antioxidant that is beneficial in many cases. Other antioxidants present in artichoke
include silymarin, and ferulic acid that assist to body protection against free radical agents.8

1.5.3 - Flavonoids

The flavonoids are the bigger group of plant polyphenols and they are subdivided into six classes.
These classes include flavonols, flavones, isoflavones, flavanones, anthocyanins and flavanols. In
globe and cardoon artichokes the main anthocyanin are cyanidin glycosides which have a violet
colour in the external bracts of some globe artichoke genotypes. The flavones indicate other
biological effects like the destruction of UV – induced skin carcinogens and vasomodulating which
are justified in vitro8.

1.5.4 – Vitamins and Minerals

Apart from the polyphenol part in artichoke, there are different minerals, vitamins and nutrients that
seem to be protective (Table 1.4). In terms of vitamins it is rich in niacin, vitamin B6, thiamine and
pantothenic acid. Minerals like copper, calcium, potassium, iron and manganese are also found.
Potassium is important because it helps in body fluids and helps to control the heart rate as well as
the blood pressure. Copper and iron are useful in the production of red blood cells and blood cell
formation respectively. 4

1.6 – Aims and Objectives

The aims of this project is to appreciate the information and knowledge obtained from literature and
find out which are the health protective compounds found in the artichoke.

The aim of the project is divided into three objectives. Such objectives include the presentation the
active compounds of the artichoke and how they show protection against different diseases such as
cardiovascular disease, diabetes and cancer.

The second objective is includes to showto put together a portfolio of the artichoke and summarise
the gained knowledge gained.

Last objective, may be used as a guide to a person that is interested to find out more information
about this specific topic.

6
2.0 Methods

The artichoke is a compound that is rich in bioactive protective compounds and can give rise to
beneficial effects and it is considered to by protective against chronic diseases. These can be
supported from different epidemiological studies that were done on humans, animals and cell
cultures.

In this research project, the effect of artichoke on cancer, cardiovascular diseases and diabetes was
examined including a research on the protective compounds such as polyphenols that include
flavonoids and caffeoylquinic acids. A search in “Web of sciences”, “Science Direct” and “Pub
Med” was done to see if the statement that artichoke has beneficial compounds is supported. The
search terms used were “Artichoke and liver disease”, “choleretic activity of artichoke”,
“Hepatoprotective activity of artichoke”, “artichoke and cardiovascular disease” and “artichoke and
cancer”.

7
Different studies were either based on humans, animals or cell cultures supported. Many results
were obtained, but, some topics were irrelevant to the topics that were searched and therefore they
were excluded.

Human studies involve different trials such as the double blind trials which include two groups; the
constituent group and the placebo group. The two groups are given randomly something to consume
without knowing what it contains and then the results are recorded. The placebo group is used in
order to have a value for comparison as well as it gives reliable and accurate results. Another type
of study could be a pilot study but is a much smaller study that can be used in clinical trials to
investigate different doses and administrations and is carried out in order to see if a full scale
project will be set.31

Animal studies, are based on animals especially rats because rats is the animal that resembles more
in human metabolism. The animals are put into an experimental room where the temperature is
optimum for them (around 20oC). People fed the animal with the extract (In this case artichoke
extract) and then the animal is screened in order to see the effects of that extract on the rats.

Also, cell culture studies on cell cultures were carried to investigate the artichoke extract on
diseases. This could be done by incubating a small artichoke extract with a human extract that has a
disease (eg: liver extract). After the incubation, these studies can show in vitro the effect of
artichoke on cell extracts as well as on animal extracts as well.

3.0 Results
Search Topic Total results Relevant Irrelevant
results results
Artichoke and Liver disease 40 22 18
Artichoke and Cardiovascular diseases 73 36 37
Artichoke and Cancer 73 30 43
Choleretic activity of artichoke 8 4 4
Hepatoprotective activity of artichoke 1 - 1
Table 2.1 illustrates all the relevant and irrelevant results that were obtained from the literature
search that was done using the search terms indicated in the Methods section. A great deal of them

8
was excluded, not only because they were irrelevant but also because there were other studies had
better quality information.

Table 2.1 – The relevant and irrelevant results that were obtained from the literature search.

Table 2.2 – Bioactive compounds present in the artichoke

Artichoke bioactive compounds
Flavonoids Phenols and Polyphenols
Luteolin 3-0 Caffeoylquinic acid (chlorogenic acid)
Apigenin 1.3-di-O-caffeoylquinic acid (cynarin)
Caffeic acid

Table 2.2 refers to all the bioactive compounds that have been found to be present in the artichoke.
The searches also revealed that these compounds had protective effects, some towards liver disease,
others against cancer or cardiovascular diseases.

As such the following tables present the data from a series of papers reporting the role of these
bioactive compounds in liver disease, cardiovascular disease and cancer.

3.1.1 – Bioactive phytochemicals present in artichoke that are effective against liver diseases –
study designs in vivo (animals).
Table 2.3 – Effect of artichoke against liver disease, in vivo
Compound Study Animal Treatment Duration Concentration Result
or pre-
study
treatment

Chlorogenic E. Speroni Rats (Male 1 week 20 minutes 48 rats used- - no significant

acid et al Sprague- prior to experiment received a dose recovery of serum
9
 (2003)29 Dawley experiment of 40 and 80 Aspartate
rats about they were mg/kg that Transferase and
150-180g) undergoing corresponds to Alanine
standard the caffeoyl transferase
diet. derivative - no choleretic
content effect
- no significant
protection in the
rat liver
Caffeoylquini E. Speroni Rats (Male 1 week 60 minutes 12 rats- given - No choleretic
c acid et al Sprague- prior to experiment a dose of 0.005 effect
derivative - (2003)29 Dowley experiment and 0.01 - no significant
Cynarin rats about they were mg/kg, recovery of serum
150-180g) undergoing corresponding Aspartate
standard to 1 and 2 Transferase and
diet. g/kg solution Alanine
of phosphoric transferase
acid (0.01 M) - not significant
protection

Table 2.3 indicates the effect of artichoke against liver disease in studies that were done in vivo.
Speroni et al (2003), tested under standardised conditions, different artichoke extracts on rats. The
rats were starved for 18 hours prior to the experiment and they were divided into groups from which
the one group was given chlorogenic acid and the other received cynarin29.

3.1.2 Bioactive phytochemicals present on artichoke that are effective against liver diseases – study
designs in vivo (humans).
Table 2.4 – Effect of artichoke against liver disease, in vivo
Compound Study Gender and Duration State of Source Result
n health

10
 Caffeoylquinic R. Huber N=17 12 weeks Chronic 10 - increases choleresis
acids including et al. Both male(8) Hepatitis C capsule in healthy volunteers
caffeic acid, (2009) 35 and female (3mornin and show
dihydrocaffeic (9). g, 3 hepatoprotective
acid, ferulic Age: 57+/- 9 lunch,4 effects
acid, dinner) - The patients were
dihydroferulic containin highly motivated with
acid g with this therapy.
artichoke - no effect on elevated
extract) aminotransferase
levels
Caffeoyl quinic G. 247 patients 6 weeks Persistent 2 Generally observation
acids, Holtmann aged between pain in the capsules, of improvement in
flavonoids et al 18-75 upper 3 times dyspeptic symptoms
(2003)36 abdomen, per day of
functional medicatio
dyspepsia n
containin
g 320 g of
artichoke
or
placebo

Table 2.4 refers to studies done on humans that showed the protective effects of artichoke
compounds. Huber et al (2009), tested different capsules that contained artichoke extract on people
that were suffering from hepatitis C. His results were positive as the choleresis increased and the
capsule showed no effect on the aminotransferase levels35.

Holtman et al (2003) examined a double blind trial to see the effect of artichoke on patients
suffering from dyspepsia. These patients were complaining about upper abdomen pain and therefore
they were given 2 capsules as medication containing 320 g of artichoke, 3 times per day. He
observed that, generally the patients showed an improvement in dyspeptic symptoms.

3.1.3 Bioactive phytochemicals present on artichoke that are effective against liver diseases – study
designs in vitro.
Table 2.5 – Effect of artichoke against liver disease, in vitro
Compound of Study Cell type Pretreatm Duration Concentr Result
artichoke ent ation
Chlorogenic Gebhardt Male Exposure 40 minutes 1.5-2.5% - Reduction of MDA
11
 acid and Sprague – of production and
Fausel Dawley rats hepatocyte inhibition of
(1997) 26 (220-300g) cultures to chemiluminescent
used as t-BMP at xanthine oxidase
isolated 0.8 mM for assay
hepatocyte 40 minutes - showed the most
donors, hepatoprotective
suspended in effects of all the
Williams bioactive compounds
medium E.
Caffeoylquinic Rolf Rats – Male 12 hour 20-60 min -1.5 - Inhibition of MDA
acid derivative Gebhardt. Sprague light and mg/ml by 7% induced by t-
- Cynarin (1997) Dawley dark cycle BHP which inhibited
(220-300g) by 11%.
act as -showed antioxidant
hepatocyte properties and
donors hepatoprotective
effect
Caffeoylquinic Gebhardt Male Exposure 40 min 0.2-0.8% - Reduction of MDA
acid derivative and Sprague – of production and
- Cynarin Fausel Dawley rats hepatocyte inhibition of
(1997) 26 (220-300g) cultures to chemiluminescent
used as t-BMP at xanthine oxidase
isolated 0.8 mM for assay
hepatocyte 40 minutes - showed the most
donors, hepatoprotective
suspended in effects of all the
Williams bioactive compounds
medium E.

Luteolin Gebhardt Male Exposure 40 min 0.2-0.8% Reduction of MDA

and Sprague – of production and
Fausel Dawley rats hepatocyte inhibition of
(1997) 26 (220-300g) cultures to chemiluminescent
used as t-BMP at xanthine oxidase
isolated 0.8 mM for assay
hepatocyte 40 minutes
donors,
suspended in
Williams
medium E.

Bioactive phytochemicals present on artichoke that are effective against liver diseases – study
designs in vitro (continued)
Table 2.6 – Effect of artichoke against liver disease, in vitro
Compound of Study Cell type Pretreat Duration Concentrati Result
artichoke ment on

Caffeic acid R. Male Exposur 40 min 1.5-2.5% Reduction of MDA

Gebhardt Sprague – e of production and
and M. Dawley rats hepatocy inhibition of
Fausel (220- te chemiluminescent
(1997) 26 300g)isolate cultures xanthine oxidase
d hepatocyte to t- assay
donors, BMP at
suspended in 0.8 mM
Williams for 40

12
 medium E. minutes
Chlorogenic Rolf Rats – Male 12 hour 20-60 Extraction -Inhibition of
acid Gebhardt. Sprague light and minutes and isolation Malondialdehyde
(1997) Dawley dark of rat (MAD) that is
(220-300g) cycle hepatocytes induced by t-BHP by
and 16% and 17%
inhibition respectively.
with - antioxidant effect
artichoke
extract for
40 minutes
(3 mg/ml)
Cynarin Rolf Rats – Male 12 hour 20-60 Extraction -hepatoprotective and
Gebhardt. Sprague light and minutes and isolation antioxidant effects
(1997) Dawley dark of rat
(220-300g) cycle hepatocytes
and
inhibition
with
artichoke
extract for
40 minutes
(3 mg/ml)

Table 2.6:

MDA= Malondialdehyde,

t-BMP= tert-butyl hydroperoxides ; solution that can be used in oxidation process

Tables 2.5 and 2.6 illustrate the effect of the artichoke extract against liver diseases on studies done
in vitro.

In addition, different studies in vitro were also carried out and can be summarised in the table 3.1.3.
Gebhardt and Fausel (1997) isolated Male Sprague Dawley rats. These hepatocyte donors were
treated with William’s medium E, and then was exposed to t-BHP cultures at 0.8 mM for 40
minutes following by 2-hour incubation. Different bioactive compounds presence in the artichoke
including chlorogenic acid, cynarin, luteolin, and caffeic acid indicated protective effects. Such
protective effects are hepatoprotective and antioxidant activity and reduction in production of
malondialdehyde (MDA). MDA can cause lipid peroxidation and damages to DNA26.

13
 Gebhardt (1997) tested the antioxidative and protective effects of artichoke extract on male
Sprague Dawley rat hepatocyte donors. The rats were kept for 12 hours in the dark and light cycle
before the experiment. Chlorogenic acid, showed a decrease in MDA and an antioxidant effect,
whereas cynarin indicated antioxidant and hepatoprotective effects27.

Bioactive phytochemicals present on artichoke that are effective against liver diseases – study
designs in vitro (continue).
Table 2.7 – Effect of artichoke against liver disease, in vitro
Compound of Study Cell type Pretreat Duration Concentr Result
artichoke ment ation

Cynarin Tomas Male 18h - 3mg/ml Hepatoprotective

Adzet et al Sprague fasted properties
(1987)37 Dawley rats before
were isolated isolation
by
collagenase

Caffeic acid Tomas Male 18h - 1 mg/ml -Hepatoprotective

14
 and derivatives Adzet et al Sprague fasted properties
(1987)37 Dawley rats before - Antioxidant activities
were isolated isolation
by
collagenase
Luteolin-7- Tomas Male 18h - 0.01 - Hepatoprotective
glucoside Adzet et al Sprague fasted mg/ml properties
(1987)37 Dawley rats before - acts exclusively upon
were isolated isolation GOT activity
by
collagenase

Table 2.7 indicates the effect of artichoke extract on studies done in vitro against liver diseases.
Tomas Adzet et al (1987), isolated Male Sprague Dawley rats after fasting them for 18 hours.
Bioactive compounds including caffeic acid, cynarin and luteolin-7-glucoside illustrated to have
protective effects against liver disease37.

3.2.1 Bioactive phytochemicals present on artichoke that are effective against cardiovascular
diseases – study designs in vitro.
Table 2.8 – Effect of artichoke against cardiovascular diseases, in vitro
Compound of Study Cell type Pre-treatment Duration Result
artichoke and
concentration
Luteolin and its Ning Xia Human 1-100 mg/mL 6 or Enhances the secretion
7-O-glucoside et al. Coronary 24hours of nitric oxide
cynaroside (2014)23 smooth
muscle cell
Luteolin Huige Li Human 10% CO2 in Incubation Increase endothelium
et al umbilical vein Dulbecco’s for 18h nitric oxide (reduced
(2004)24. endothelial modified CVD)
cells Eagle’s medium
(Sigma)

15
 Luteolin Rolf Cultured Rat Williams E Incubation - Inhibition of
Gebhardt hepatocytes medium for 2 hours cholesterol.
(1998)12 - blocked cholesterol
biosynthesis especially
in the presence of
insulin
- monophasic
Luteolin Wang et Cultured Rat 500-1000 mg of - total - antioxidant activity
al.(2003)38 hepatocytes extract with running
100mL. 60% time:25
methanol mins

Chlorogenic Wang et Cultured Rat 500-1000 mg of - total - antioxidant activity

acid al.(2003)38 hepatocytes extract with running
100mL. 60% time:25
methanol mins

Table 2.8
The Williams solutions contained 10 % newborn calf serum, 2 mM glutamine, penicillin
(50 U/ml), streptomycin (50 mg/ml) and 1027 M dexamethasone

The effect of artichoke extract against cardiovascular diseases can be shown on table 2.8 in vivo.

Starting with the in vitro studies, Xia et al23 investigated the effect of artichoke extract on human
coronary smooth muscle cell. They observed that luteolin and its 7-O-glucoside cynaroside
enhanced the secretion of nitric oxide. Nitric oxide is found on the surface of blood cells and when
it is present it increases the blood flow. By increasing the blood flow, the oxygen uptake increases
as well and this makes the heart functioning more efficient.

In addition to cardiovascular diseases, Huige Li et al24, analysed the effect of artichoke extract on
human umbilical vein endothelial cells using supplemented with 10% fetal bovine serum, 2 mM L-
glutamine, 1 mM sodium pyruvate, 100 U/ml penicillin, 100 g/ml streptomycin, and 1
hypoxanthine, amethopterin/methotrexate, and thymin. Their results showed that various
polyphenols increased the effect of nitric oxide on endothelium cells, particularly by luteolin.
Cynaroside was also found to increase nitric oxide24.

Furthermore, Wang et al, investigated 500-1000 mg of artichoke extract on cultured rat hepatocytes
and found that chlorogenic acid and luteolin have antioxidant activities. Antioxidant activities of
16
artichoke extracts can result in the lowering of cardiovascular disease. This is because, by having
antioxidant activities, they will prevent the oxidation of LDL on the endothelium cells.

Gebhardt12, examined the effect of artichoke on cultured rat hepatocytes, after 2 hour incubation
with Williams E medium. Luteolin was found to reduce cholesterol and blocks cholesterol
biosynthesis particularly in the presence of insulin. By lowering the cholesterol levels, especially
LDL cholesterol, cardiovascular diseases can be reduced as well. Cynarin and caffeic acid though
showed no effect at all.

Bioactive phytochemicals present on artichoke that are effective against cardiovascular diseases –
study designs in vitro (continue).
Table 2.9 – Effect of artichoke against cardiovascular diseases, in vitro
Compound of Study Cell type Pre-treatment Duration Result
artichoke and
concentration
Chlorogenic Rolf Cultured Rat 100 mg of Incubation - inhibition by 15% at
acid Gebhardt hepatocytes artichoke was for 2 hours 100 mg/ml
(1998) mixed with - small inhibition effect
Williams E -
medium
Chlorogenic Andrea Plant cells - - - antioxidant activities
acid Moglia et
al (2008)32

Chlorogenic Andrea Plant cells - Free radical

acid, luteolin Moglia et scavengers
glucosides and al (2008)32
dicaffeolquinic
acid

17
 Apigenin Wang et al Cultured Rat 500-1000 mg of - total - Antioxidant activity
(2003)38 hepatocytes extract with running
100mL. 60% time:25
methanol mins
Cynaroside Li, Xia, Human 10% CO2 in Incubation Increase endothelium
Isolde umbilical vein Dulbecco’s for 18h nitric oxide (reduced
Brausch, endothelial modified CVD)
Ying Yao cells Eagle’s medium
and Ulrich (Sigma)
Forsterman supplemented
n (2004)24 with 10% fetal
bovine serum

In vitro studies can also be seen in table 2.9 where the effect of artichoke against cardiovascular
diseases is shown.
12
Rolf Gebhardt et al , analysed the effect of artichoke on cultured rat hepatocytes following
incubation for 2 hours using William solution E containing 10% newborn calf serum, 2 mM
glutamine, penicillin (50 U/ml), streptomycin (50 mg/ml) and 1027 M dexamethasone. Chlorogenic
acid found to inhibit cholesterol levels.

32
Andrea Moglia et al , examined the plant cells and he observed that chlorogenic acid has
antioxidant activities as well as Chlorogenic acid, luteolin glucosides and dicaffeolquinic acid can
act as free radical scavengers32. In addition, Wang et al.38 investigation showed the antioxidant
effects of apigenin38.

Bioactive phytochemicals present on artichoke that are effective against cardiovascular diseases –
study designs in vitro (continue).
Table 2.10 – Effect of artichoke against cardiovascular diseases, in vitro
Compound of Study Cell type Pre-treatment Duration Result
artichoke and
concentration

Quercetin, Laura Chinese 10% heat 30 minutes - Electrophilic

luteolin vicedo hamster ovary inactivated fetal compounds that could
Jacociunas cells bovine alkylate DNA
et al. serum,2mM L-
(20126 glutamine, 100
U/ml penincilin
and 100 μg/ml

Cynarin Wang et al Cultured Rat 500-1000 mg of - total Highest antioxidant

(2003) 38 hepatocytes extract with running activity
100mL. 60% time:25
methanol mins

18
 Cynarin and Rolf Cultured Rat Williams E Incubation - no effect at all
caffeic acid Gebhardt hepatocytes medium for 2 hours
(1998)

Table 2.10
William’s solution contains 10% newborn calf serum, 2 mM glutamine, penicillin (50
U/ml), streptomycin (50 mg/ml) and 1027 M dexamethasone

Additionally, the effect of artichoke against cardiovascular diseases can be shown in vitro in Table
2.10.

Wang et al.38 reported that Cynarin showed to have the highest antioxidant activity of all the
compounds38. In addition, Laura Vicedo Jacociunas et al 6, assay the effect of artichoke on Chinese
hamster ovary cells and it was observed that Quercetin and luteolin can show electrophilic
compounds that could alkylate DNA6.

3.2.2 Bioactive phytochemicals present on artichoke that are effective against cardiovascular
diseases – study designs in vivo (animals).
Compound Study Animal Pre-treat Duratio Concentra Result
n tion
Luteolin Zhiyi Golden Access to food 0.08–10.65 - Inhibits the biosynthesis of
Qiang et Syrian and water in a mg/g 14C-acetate
al11. hamsters temperature - reduced oxidised LDL
(male controlled room -HMG-CoA reductase inhibitory
weight with a light– effect
approxima dark cycle of 12 -
tely 115 g, h.
female
weight
approxima
tely 95 g, 8
week old)
Luteolin Saenz Male Fed on standard 0.5% - Protect low density lipoprotein
Rodriguez Wistar rats chow diet, from oxidation
et al. fasted overnight - decrease hepatic cholesterol
(2002)33 and have free synthesis
access to water
Hydroxyci Antonio Male Free access to - 1g - Protects the protein from
19
nnamic Jimenez- Wistar rats food and water oxidation
acid Escrig et (n=20)
al. (2003)34
Chlorogeni Antonio Male Free access to 1g - Antioxidant activities
c acid, Jimenez- Wistar rats food and water
cynarin,lut Escrig et (n=20)
eolin al. (2003)34
Chlorogeni Zhiyi Golden Access to food 0.3–18.3 HMG-CoA reductase inhibitory
c acid Qiang et Syrian and water in a mg/g effect
al11. hamsters temperature
(male controlled room
weight with a light–
approxima dark cycle of 12
tely 115 g,
female
weight
approxima
tely 95 g, 8
week old)
Table 2.11: effect of artichoke against cardiovascular diseases in vivo.

Studies in vivo were also done in order to see the effect of artichoke against cardiovascular disease.
Zhiyi Qiang et al11, examined on golden Syrian hamsters the effect of 0.08-10.65 mg/g of artichoke.
It was concluded that luteolin can decrease cardiovascular diseases. This can be done by inhibiting
the biosynthesis of 14C-acetate and also reduce the LDL oxidation.

Antonio Jimenez-Escrig et al34, saw that hydroxycinnamic acids can protect against protein
oxidation. Protein oxidation can result in atherosclerosis, diabetes and other neurological diseases.
If protein oxidation is inhibited then, cardiovascular diseases can be prevented. He also concluded
that chlorogenic acid, cynarin and luteolin showed antioxidant activities.

33
Moreover, T. Saenz Rodriguez et al assay the effects of artichoke on cardiovascular disease on
male Wistar rats. It was illustrated that luteolin, can show protection of low density lipoprotein
against oxidation and also, decreases the hepatic cholesterol synthesis33.

Also, Zhiyi Qiang et al11, analyse the effect of 0.3-18.3 mg/g artichoke on golden Syrian hamsters.
The hamsters had free access to food and water. It was deduced that, chlorogenic acid, indicated the
reduction of HMG-Co A which is responsible for the synthesis of cholesterol.

20
Table 2.11:
HMG-CoA reductase: HMG-CoA is the enzyme responsible for the production of cholesterol in the
liver. This enzyme is inhibited
3.2.3 Bioactive phytochemicals present on artichoke that are effective against cardiovascular
diseases – study designs in vivo (humans).
Table 2.12 – Effect of artichoke against cardiovascular diseases, in vivo
Compoun Study Gender Duratio State of Food Source Result
d and n n health frequencey
questionnai
re (FFQ)
Luteolin Bundy et Male 6 weeks Random Yes- asking Capsule -decrease in the
al. (n=14) selection on mood of ALE total cholesterol
(2008)43 Female and containi (significant
(n=24) symptoms ng 2.5% difference of 6.1%.
total p=0.025)
caffeoyl - no statistical
quinic difference in the
acids HDL concentration
and - increase in biliary
0.1% secretion
luteolin

Table 2.12
ALE= Artichoke Leaf Extract
HDL= High density Lipoprotein

21
In addition to in vivo animal studies, there are also in vivo human studies which can be shown in
table 2.12. R. Bundy et al 43, detected the effect of artichoke on human. They were given capsules
with artichoke extracts that contain an amount of caffeoylquinic acids and luteolin. A significant
difference (6.1%) in total cholesterol (p=0.025) and an increase in biliary secretion was observed.

3.3.1 Bioactive phytochemicals present on artichoke that are effective against cancer – study
designs in vitro.
Table 2.13 – Effect of artichoke against cancer, in vitro
Compound of Study Cell type Pre-treatment Duration Result
artichoke and
concentration
Chlorogenic Stefania Rat Collagenase in - - Increase dead cancer
acid Miccadei hepatocytes Williams E cells
et al medium - reduces MDA
(2008).28 production
- prevents the loss of
GSH
Chlorogenic Stefania HepG2 cells 10% fetal calf - - Apoptosis in cancer
acid with Miccadei (human serum, cells (HepG2)
artichoke et al hepatoma cell penincillin, - Artichoke extract
extract (2008)28. line) streptomysin showed apoptosis but
chlorogenic acid does
not kill the HepG2 cells
at the same incubation
time.
Caffeic Stefania Rat Collagenase in - - showed antioxidant
acid/chlorogenic Miccadei hepatocytes Williams E activity
acid/ ferulic et al medium
acid (2008).28

22
 Clorogenic acid, Anna Breast cell 200-1200 - Induces apoptosis of
caffeic acid, Maria line μM breast cancer cell
ferulic acids, Mileo et
artichoke al16
extract
Apigenin Ela Nur DLD1 - - apoptosis on cancer
Simsek* colorectal cells
Tuna Vysal cancer cell
(2013)21 line

Apigenin Zhong et al HCT-116 McCoys 5A 25 -apoptosis

201017 cells medium with mg/kg or - suppressed tumor
fetal bovine formation
serum and
50mg/kg
gentamicin
Hydroxycinnam S. Nadova Murine L1210 10% FCS, 100 3.44% - antiproliferative
ic acid et al. leukemia cells U/ml activity
(2007)18 penincillin, - chemotherapeutic
streptomycin , effects that cause
glutamine in apoptosis
atmosphere with
5% CO2

Table 2.13:
HepG2 = cell culture that is used during in vitro studies, to see the effect of a compound
on cancer (carcinogenic hepatocyte cells).
MDA= Malondialdehyde

Compounds in the artichoke can show health protective activities against cancer. Different vitro and
in vivo studies were done in order to support the above statement. This can be shown in tables 3.2
and 3.3.

Stefania Miccadei et al 28, investigated the effect of artichoke on both rat hepatocyte isolation and
on HepG2 cells (human hepatoma cell line). It was concluded that on isolated rat hepatocytes,
chlorogenic acid can show effects by causing apoptosis in cancer cells. And by preventing the loss
of GSH. Moreover, caffeic acid, chlorogenic acid and ferulic acid showed antioxidant activity. On
human cells, chlorogenic acid and artichoke extract, cause death to cancer cells. The artichoke
extract, displayed apoptosis but the chlorogenic acid does not cause apoptosis at the same
incubation time28.

21
Additionally, E.N. Simsek and T. Vysal make an investigation on DLD1 colorectal cancer cells
and it was observed that apigenin causes induction at p21 and NAG-1 on the cancer cells. The last
one was also seen by Zhong et al 17.

18
S. Nadova et al , looked the effect in murine L1210 leukaemia cells and it was reported that
hydroxycinnamic acid can have chemotherapeutic effects by causing apoptosis18.
23
 Compound Study Animal Pre-treat Durati Concentrati Result
on on

Silymarin Rajesh Six week Electric 30 - inhibitory effect on

Agarwal old clippers second TPA-induced epidermal
et al. femal applied 1 day s ODC
(1994)19 SENCA before the - strong anti-oxidant
R mice experiment. properties
from Treated with - anti-tumor promoting
Harlen skin tumor effect
Sprague promoters in
Dawley acetone or
silymarin
3.3.2 Bioactive phytochemicals present on artichoke that are effective against cancer – study
designs in vivo.
Table 2.14 – Effect of artichoke against cancer, in vivo

24
The effect of artichoke extract against cancer was studies in vivo and this can be indicated in the
table 2.14. In vivo study done by Rajesh Agarwal et al (1994), was positive as silymarin showed an
inhibitory effect on TPA-induced epidermal ODC, and also strong anti-oxidant and anti-tumour
effects.19

4.0 Discussion:

This dissertation focuses on the health protective compounds of globe artichoke. As highlighted
artichoke contains a range of bioactive protective compounds that can be beneficial against cancer,
cardiovascular diseases and liver disease. Supporting evidence was found in scientific studies both
in vitro and in vivo.

It was evident that large number of scientific publications were associated with the hepatoprotective
activity of caffeoylquinic and dicaffeolquinic acid are found to give the largest results in both in
vivo studies and in vitro studies.

25
Adzet et al37, showed in vitro the hepatoprotective activity against CCL4 toxicity of range of
artichoke polyphenols including cynarin, luteolin-7-glucoside and caffeic acid. CCL4 is acutely
toxic, which gives an increase in serum transaminases that induce liver injury, and its toxic effects
can be given by glutamate oxaloacetate transferase and glutamate pyruvate transferase. Cynarin and
caffeic acid, showed the highest hepatoprotective activity because they have an antioxidant activity
and they prevent the activity of CCL4, which challenges the oxidation of the phospholipids that
make up the liver lipid membrane37. By inhibiting the activity of CCL4 means that the phospholipids
cannot be oxidised and thus damage of the liver will be avoided. Cynarin was tested in a range of
concentrations 0.01, 0.1, 1, and 3 mg/ml but only in 3mg/ml showed the maximum antioxidant
effects against liver damage. 3mg/ml is 5800 μmols/L which is actually a very high concentration.
In the other concentrations which are lower, there was not effect at all. Isochlorogenic acid causes
the glutamic Oxaloacetic translaminase (GOT) to increase and this can help in the indication of
liver disease because it is a biomarker. During the same study, it is reported that cynarin can be
hydrolysed to caffeic acid during incubation, which was found to have hepatoprotective activity at a
dose of 1 mg/ml.

Additionally, CCl4 can cause severe hepatic damage like viral hepatitis. Sue Z-X et al 39found that
due to it's strong anti-oxidative activity, chlorogenic acid has been shown be protective towards
CCl4 which can induce liver damage39.

Different in vivo studies were also been done to show that artichoke contains bioactive protective
compounds. Huber et al35, tested artichoke capsules on people suffering from chronic hepatitis C.
He concluded that caffeoylquinic acids including caffeic acid, ferulic acid, dihydroferulic acid were
found beneficial. This is because the volunteers with Hepatitic C showed hepatoprotective effects
and they also had increase in choleresis. However, there was no effect reported on aminotransferase
levels. Alanine transaminase which can be used as a biomarker of liver disease. There are normal
ranges for this enzymes, and if its found above the range it indicates liver damage. Since no effect is
observed, the effects of artichoke are unclear.

Holtmann et al36 tested patients a high degree of abdominal pains and dyspepsia. Patients were
given randomized artichoke leaf extract. They generally observed an improvement in dyspeptic
symptoms but there was no report on specific flavonoids except caffeoylquinic acid.36

Gebhardt 27, also showed that the MDA was reduced in the presence of caffeic acid, chlorogenic
acid and cynarin, indicating again the hepatoprotective effects27. However, positive effects were
only evident when the phenolic compounds concentrations were very high. This paper can be
criticised in that a range of concentrations should be used. Nevertheless, xanthine oxidase levels

26
were reduced by and this could due to the presence of caffeic acid which can have an inhibitory
effect against that enzyme40.

However, Speroni et al29, carried out an analysis on rats using four different artichoke extracts.
Chlorogenic acid (40 and 80 mg/kg) and cynarin (0.005 and 0.01 mg/kg) did not show choleretic
effect which is the increase in the bile secretion or protection on the rat hepatocytes at all. This
difference from the other studies, could be because the concentrations used were very small.

It was also evident in other studies done by K. Janbaz40 that caffeic acid offers hepatoprotection by
inhibiting the effect of CCL4. This is thought to happen because the rise of serum transaminase
levels (including AST and ALT) is prevented by caffeic acid. Caffeic acid was found to inhibit
xanthine oxidase which is an important producer of superoxide. These actions together may be
important in the antioxidant activity of caffeic acids.

Gebhardt and Fausel26 investigated the effect of artichoke polyphenols and flavonoids on isolated
rat hepatocytes. Before exposing the hepatocytes to artichoke extract, t-BMP was added which
causes oxidation processes and this is measured as lipid peroxidation. Lipid peroxidation causes cell
damage which results in increased lactose dehydrogenase (LDH) leakage. LDH is an enzyme that is
present in many tissues and organs including the heart, liver and blood cells and this enzyme can be
used to monitor how far the individual is from getting liver disease or kidney damage is 25. In these
experiments they added polyphenol and flavonoid concentrations in a range of 1.5-2.5% and 0.2-
0.8% respectively. Their study can be considered to be reliable because a range of concentrations
was used and therefore the effect of artichoke components could be assessed at each concentration.
It was found that both flavonoids and polyphenols like chlorogenic acid, cynarin and luteolin
resulted in a reduction in the MDA production. MDA acts as a biomarker of oxidative stress,
therefore if it is reduced, the oxidative stress is prevented leading to a healthier liver. Also, the LDH
leakage reduced indicating that there was a hepatoprotective activity of cynarin, chlorogenic acid
and luteolin. They can be considered as antioxidants as they prevent oxidative stress and lipid
peroxidation26.

The bioactive compounds in the artichoke, can also act as antioxidants in the plasma. By acting as
antioxidants, they can prevent the LDL oxidised leading to the prevention of atherosclerosis. In
addition, artichoke constituents can also reduce the LDL cholesterol levels, suggesting that
cardiovascular diseases incidence can also be reduced.

Luteolin appears to have the most publications relating to its effects on cardiovascular protection.
Xia et al 23 found that luteolin and its glucosides can enhance the secretion of nitric oxide by human
coronary smooth muscle cells23. Nitric oxide can be found on the surface of endothelial cells and is
27
very protective, causing the vessels to dilate promoting the blood flow. The increase in blood flow
can lead to more sufficient oxygen uptake and therefore, better heart functioning. The same results
24
were also obtained by Li et al who tested luteolin on the human umbilical vein endothelial cells.
A range of concentrations of 0-100 μg/ml was used and it was obtained that luteolin can increase
the eNOS promoter activity in a concentration-depended manner. Gebhardt 12, found that luteolin
can block the biosynthesis of cholesterol especially under the presence of insulin. The effect of
luteolin though, should be tested without the presence of insulin in order to evaluate the effect of
this flavonoid alone. However, he also found that chlorogenic acid can inhibit the cholesterol
biosynthesis but its effect is small, it reached 15% inhibition at 100 mg/ml.

The antioxidant activities of the constituents artichoke were supported by in vitro studies as well.
32
For example, Moglia et al observed that chlorogenic acid can act as an antioxidant, but she also
observed that chlorogenic acid along with luteolin and dicaffeolquinic acid can act as free radical
scavengers32.

The antioxidant activity of luteolin, cynarin, apigenin and chlorogenic acid was also reported by
Wang et al38. Wang et al.38 reported that cynarin showed the highest antioxidant activity in rat
hepatocyte models. However, not all the have shown positive results 38. For example, Gebhardt 12,
investigated cynarin and caffeic acid on rat hepatocytes, but no effects were observed. Despite this,
they observed beneficial effects of luteolin and chlorogenic acid in this model. They reported that,
despite the fact that chlorogenic acid was present four times more than luteolin, the latter had a
bigger inhibitory effect on cholesterol synthesis and this is because luteolin can be secreted from
cynarside under physiological condition, therefore if secreted, the concentration can increase. 12

Moving on to studies carried out in vivo, again luteolin appears to have the largest number of
scientific publications in both animals and humans. Luteolin, has been shown to have a beneficial
role in the inhibition of cholesterol biosynthesis. The flavone is secreted into the digestive tract,
liver cells and other cells from its glucosides by the enzyme β-glucosidase. This is supported by
11
animal studies done by Qiang et al that luteolin, inhibits the biosynthesis of cholesterol by 60%
and inhibits the 14C- labelled acetate. The principal enzyme in the cholesterol synthesis is HMG-
CoA reductase and it is the enzyme that luteolin acts upon, in order to reduce cholesterol
biosynthesis. However, other inhibition mechanisms may also be activated and this could play a
role in the inhibition. It was shown by Qiang et al11 that the plasma lipid peroxidation was
diminished which can be directly proportional to the inhibition of atherogenesis that is correlated to
the lipid oxidation11. Although luteolin indicated that is a bioactive compound, it is worth
mentioning that the concentrations used in the study were very high (0.08mg/g-10.65mg/l= 2790-
37206 μmols/L) compared to that of the blood (1 μmols/L). If much lower concentration was used,
28
luteolin might not show protective effects. HMG-CoA reductase activity can also be reduced by
chlorogenic acid.

Rodriguez et al 33, supported that luteolin again shows protection of low density lipoprotein from
being oxidised. If LDL cholesterol gets oxidised on artery wall, atherosclerosis will follow. Also, a
decrease in the hepatic cholesterol synthesis was seen.

Furthermore, in vivo studies carried out in humans, have shown healthy effects against CVD. A
43
randomised double blind controlled trial was done by Bundy et al that included 14 Male and 24
Female. The subjects were randomly assigned to either placebo or a polyphenol containing capsule.
The capsule contained luteolin and caffeoylquinic acid concentrations of 0.1% and 2.5%
respectively. This concentration of luteolin (0.1%) is equivalent to 3.500 mmoles/L and the
concentration of chlorogenic acid is 70 mmoles/L. The plasma maximum chlorogenic acid
concentration in other studies has been shown to be up to 120 nM of which 1-2% is excreted in
urine. This is quite a low concentration, nevertheless this study found that the plasma cholesterol
decreased. Plasma total cholesterol showed a decrease from 7.16 (0.62 mmols/L) to 6.86 (0.68
mmols/L). By using baseline values showed a significant difference of 6.1% in the total cholesterol
and increase in biliary secretion were reported. This decrease in the cholesterol levels is most
12
probably due to luteolin because as said above, the study done by R. Gebhardt et al indicated that
luteolin can inhibit HMG-CoA reductase which is the enzyme responsible for the cholesterol.

Atherosclerosis, diabetes and other neurological diseases can be caused when specific proteins are
oxidised. Hydroxycinnamic acid has been shown to be protective against protein oxidation and this
has been supported by the work of Jimenez-Escrig et al .34 They also reported that chlorogenic acid,
cynarin and luteolin indicated antioxidant activities inhibiting the protein oxidation on Male Wistar
rats.

Cancer is the leading cause of death in many countries and therefore attention has been fpcised on
cancer prevention and treatment in the recent years13. Under the search term “artichoke and cancer”
or “anticarcinogenic activity of artichoke”, the results were surprisingly few. Although the results
were few, they showed positive effects against cancer. Studies in vitro done by Miccadei et al 28,
indicated the effect of artichoke on both rat hepatocytes and on human hepatoma cells known as
HepG2. It was observed that chlorogenic acid causes apoptosis against cancer cells meaning that it
kills cancer cells. This is very important because if the cancer cells undergo apoptosis, the
individual may cured. Also chlorogenic acid is found to be protective towards GSH which is an
antioxidant and is very important in the cells particularly where the concentration is 5mM. By
preventing the loss GSH, artichoke leaves found to be protective against oxidative stress as well. In

29
addition to this, hydroxycinnamic acids including caffeic acid, chlorogenic and ferulic acid appear
to have antiproliferative activity. The hydroxycinnamic acids referred above appeared to act as
antioxidants as well leading to anticarcinogenic activities. Their antioxidant activity is a result of
their chemical structure and is explained by their ability of scavenging free radicals. There is
evidence that the hydroxycinnamic acids have inhibitory effect on cancer cells. There are many
studies in vitro that were done that showed the anticarcinogenic effect of the hydroxycinnamic acids
against colon cancer, liver cancer, gastric cancer, prostate, breast and lung cancer13.

14
Wang et al , investigated the effect of caffeic acid phenethyl ester on HCT116 cells. It was
observed that caffeic acid reduced the b-catenin protein expression which is a protein responsible
for the cell-cell adhesion and mutations in cancer. By reducing this protein, the antiproliferative
activity increases. Caffeic acids appeared to show a decrease in tumour development as well as
increase in apoptosis14. Another study that was demonstrated by Weng and Yen 15, showed the
chemoprotective effects of the phytochemicals chlorogenic acid and caffeic acid against cancer
invasion and metastasis. It was concluded that caffeic acid, inhibited the CT26 cell invasion that can
lead to colon cancer. For liver cancer it was found that the chlorogenic acid and caffeic acid can act
as anti-invasive on the rat hepatoma cell live (AH109A) and this was supported in vitro.
Chlorogenic and caffeic acid can destroy Hep3B cells and HepG2 respectively. Caffeic acid can be
protective against prostate cancer as well and can be responsible for the inhibition of PC3 cells.

Nadova et al 18 investigated the inhibitory effect of artichoke on leukaemia cells. The results showed
that hydroxycinnamic acid showed antiproliferative activity which means that it does not allow to
the cancer cells to multiply. Additionally, hydroxycinnamic acid can show cytotoxic effects against
leukaemia cells at a concentration of 3.44%18.

Mileo et al 16, showed that polyphenols found in the artichoke can cause apoptosis towards breast
cancer cells. Cancer metastasis is the stage where the cancer cells can move from the primary stage
to second stage where the formation of tumours occur. Mileo et al 16 found that the artichoke extract
inhibited the metastasis of cancer on breast cells. Chlorogenic acid, ferulic and caffeic acid were
used at a concentration ranging of 200-1200μM and are found to have antitumor activities and
antioxidant activities causing apoptosis to cancer cells at a concentration of 800 μM which is
relatively high concentration.

It was supported that the use of Bax and Bc12 plays a crucial role. Bax causes cell apoptosis where
Bc12 protects the cells from undergoing apoptosis. Bc12 is supported to be the pathway where
artichoke extracts induce apoptosis to the cancer cells. Mileo et al12, supported that induction of p21

30
gene along with the artichoke extract induces apoptosis, more studies are needed to support the
above statement16.

Colorectal cancer cell apoptosis was supported by Simsek E.N and Uysal T20, which make an
investigation to see the apoptotic effects of artichoke on those cells. DLD1 cells were used and it
was found that apigenin has anticarcinogenic activities. Apigenin is a flavonoid that can be anti-
mutagenic, and anticarcinogenic. This was also supported by Zhong et al 17 which make a study on
the effect of apigenin (25 mg/kg or 50mg/kg) on colorectal cancer cells. It was concluded that
apigenin can cause apoptosis to HCT-116 cancer cells. 25 mg/kg can be consider as a low
concentration where 50 is considered high concentration. It was also concluded that it inhibited
tumour formation17.

Antioxidant effects can be shown by silymarin which is another constituent of artichoke. Agarwal
et al 19 saw that the effect of silymarin on cancer. Silymarin have very strong antioxidant properties
and can act as anti-hepatotoxic. It offers inhibition to TPA. Silymarin can possess anti-tumour
function against tumour promoters19. This is because the major component of silymarin is silibin
which induces strong anti-cancer effects and can inhibit the cancer cell proliferation by blocking the
cell cycles at G1 and G2 reported by Ge et al 41.

The beneficial effects of the bioactive artichoke compounds against liver disease, CVD and cancer
that were described can be summarized in the table 3.0.

Some articles may be conflicting but despite this, it can be concluded that the artichoke contains
bioactive compounds that show health protective activities. Studies in vivo and in vitro supported
this statement, however more evidence is also needed. Studies in vitro can be considered to give
overestimated or underestimated results because different substances and chemicals can also be
used and may have an impact on the results.

31
 Effect of artichoke compound on the diseases
Bioactive compound Liver damage CVD Cancer

Chlorogenic acid i) MDA Inhibition i) Antioxidant i) Cancer cell

ii) Free radical apoptosis (breast
savenging cancer)
ii) Increase the
number of cancer
cell deaths
Luteolin i) Acts on GOT i) Increases Nitric -
activity Oxide
ii) Reduces MDA ii) Blocks
cholesterol
biosynthesis
iii) Antioxidant
activities
iv) Protects LDL
oxidation
v) Inhibits 14C
acetate
vi) Free radica
scavenging
Cynarin i) Inhibition and i) Antioxidant -
reduction in activity
MDA
ii) Antioxidant
activity

Apigenin - i) Antioxidant i) Cancer cell

activity apoptosis
Caffeic acid i) Increase - i) Antioxidant
choleresis (bile activity
acid secretion)
ii) Reduced MDA
and inhibits
xanthine
oxidative assay
iii) Antioxidant
activity
Hydroxycinnamic acid - i) protects against protein i) Antiproliferative
oxidation activity
ii) Chemoprotective
effects
Cynaroside - i) Increase nitric
Oxide
Silymarin - - i) Antioxidant and
anti-tumour
activities
Table 3.0 – Summary of the effect all the bioactive artichoke compounds

32
5.0 Limitations

Doing this literature dissertation, there were different limitations that came across. Firstly there
were time constrains. Due to time constraints, only two scientific search data bases were used and
there are in fact several more that could have been searched in. Additionally, it was hard to perform
a prober comprehensive situation as the articles and journals were very long, and we attended
university lectures as well.

Moreover, there were a lot of journals that were unavailable and this was difficult as the full
information on the topic was important for the study. Furthermore, there was a limitation regarding
the search terms, for instance “Liver disease”, is also called “Hepatic disease”. Therefore, if “liver
disease” was searched, the study results done on “hepatic disease” would not come up as they are
named differently.

33
6.0 Conclusion

Globe artichoke is rich in medicinal substances and is considered as an herbal medicine 21. Artichoke
is a good source of many flavonoids and phenols that can be beneficial antioxidants and can be
favourable against different diseases including liver disease, cardiovascular disease and cancer.
They possess health protective effects and can give health benefits for humans. All these research
done suggests that consumption of vegetables especially artichoke can be directly proportional to
health benefits. Artichoke is very rarely eaten, therefore people must be informed of its healthy
substances so they start to eat it more often, maybe once a week, as most people do not like it.
Although, there are different artichoke capsules that can be obtained by people that do not like
eating it, it is better to eat the whole food.

Clinical and non-clinical trials have confirmed the therapeutic effects of the globe artichoke.

It is supported by Vincenzo Lattanzio et all22 that among all the plants against liver complains,
globe artichoke is assumed to be the most efficacious.

Artichoke extract is considered to have a cardio protective effect and can have lipid-lowering effect.
According to K. Kraft20 study, artichoke can reduce the atherosclerosis by reducing the cholesterol
synthesis and by the inhibition of LDL oxidation by the bioactive compounds present.

Anti-carcinogenic effect of the artichoke was also improved by studies in vivo and in vitro.
Phenolic acids present in the artichoke can inhibit invasive and metastatic behaviours of cancer
cells. It is recommended that a daily consumption of vegetables that contain phenols can impede
metastasis of cancer cells15.

It was also suggested by E.N. Simsek and tuna Uysal21 that because artichoke has beneficial
chemical effects against cancer, in future it can be used in the establishment of anticancer drugs.

34
7.0 Acknowledgement:

I would like to thank my supervisor Dr Jonathan Brown for all his support, his patience and caring
throughout the dissertation. He was always listening to me, supporting and encouraging me to
continue the hard work, as it was the first time that I was doing such a long research project.

35
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