Effect of Gundelia tournefortii L. extract on lipid profile and TAC in patients with coronary artery disease: A double-blind randomized placebo controlled clinical trial

Accepted Manuscript Title: Effect of Gundelia tournefortii L. extract on lipid profile and TAC in Patients with Coronary Artery Disease: A double-blind randomized placebo controlled clinical trial Author: Fatemeh Hajizadeh-Sharafabad Mohammad Alizadeh Mir Hosein Seyyed Mohammadzadeh Saeedeh Alizadeh-Salteh Sorayya Kheirouri PII: DOI: Reference:

S2210-8033(16)30004-5 http://dx.doi.org/doi:10.1016/j.hermed.2016.02.001 HERMED 129

To appear in: Received date: Revised date: Accepted date:

24-6-2015 21-9-2015 4-2-2016

Please cite this article as: Hajizadeh-Sharafabad, Fatemeh, Alizadeh, Mohammad, Mohammadzadeh, Mir Hosein Seyyed, Alizadeh-Salteh, Saeedeh, Kheirouri, Sorayya, Effect of Gundelia tournefortii L.extract on lipid profile and TAC in Patients with Coronary Artery Disease: A double-blind randomized placebo controlled clinical trial.Journal of Herbal Medicine http://dx.doi.org/10.1016/j.hermed.2016.02.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Type of article: Original Research Effect of Gundelia tournefortii L. extract on lipid profile and TAC in Patients with Coronary Artery Disease: A double-blind randomized placebo controlled clinical trial Fatemeh Hajizadeh-Sharafabada, Mohammad Alizadehb*, Mir hosein Seyyed Mohammadzadehc, Saeedeh Alizadeh-Saltehd, Sorayya Kheirourie a

MSc Student, Student Research Committee, Faculty of Nutrition, Tabriz University of

Medical science, Tabriz, Iran . b

Department of Nutrition, Faculty of Nutrition, Tabriz University of Medical science, Tabriz,

Iran. c

Department of Cardiology, Faculty of Medicine, Uremia University of Medical Sciences,

Uremia, Iran. d

Department of Horticultural Sciences, University of Tabriz, Faculty of Agriculture, Tabriz,

Iran. e

Department of Nutrition in Community, Faculty of Nutrition, Tabriz University of Medical

science, Tabriz, Iran.

*Corresponding author: Mohammad Alizadeh , MD., Ph.D. Associate Professor Department of Nutrition, Faculty of Nutrition Tabriz University of Medical Sciences Ghol-Ghashtst. Tabriz, I. R. Iran. ZIP Code: 5166614711 Tel: +98-411-3376228 E-mail: [email protected], [email protected]

Running title: Gundelia tournefortii on lipid profile and TAC

Abstract Context: Gundelia tournefortii (GT) has been known to possess hypolipidemic and antioxidant activities. Objective: This study was carried out to evaluate the effects of GT on total antioxidant capacity (TAC) and lipid profile in patients with coronary artery disease (CAD). Materials and methods: A total of 38 angiographically confirmed CAD patients were enrolled in this randomized, double-blind, clinical trial. The subjects consumed G. tournefortii extract (GTE) or placebo for 8 consecutive weeks. Serum total cholesterol, triglyceride, high density lipoprotein-cholesterol (HDL-c), low density lipoproteincholesterol (LDL-c) and TAC were determined by conventional methods. In addition, dietary intake was recorded using 24-h recall method and converted into nutrients with software Nut4 version1. Results: At the end of the study, the GTE group had recorded a significantly lower energy intake compared to the placebo group (p=0.04). The BMI also significantly decreased in the GTE group by 3% (from 26.5±3.6 kg/m2 at baseline to 25.9±3.6 kg/m2 at the end of the trial). There was a significant reduction in total cholesterol level in the GTE group (151±23.8 mg/dl at baseline to 131.1±25.9 mg/dl at the end of the trial), however, its level increased slightly in the placebo group (133.5±22 mg/dl at baseline to 141.4±22.4 mg/dl at the end of the trial). The mean value of LDL-c level notably decreased in the GTE group from 86±26 to 60.58±29.9 mg/dl (p=0.001). No significant differences were observed in the groups for HDL-c or triglyceride levels; however, TAC significantly changed in the two groups after the intervention. Conclusion: The intervention resulted in a statistically significant difference in total cholesterol, LDL-c and BMI suggesting that GTE may be an appropriate adjunctive medicinal plant to help reduce the major risk factors of CAD. Key terms: total antioxidant capacity, cholesterol, body mass index, adjunctive medicinal plant

Introduction Coronary artery disease (CAD) is one of the major underlying global causes of death (Bundy et al., 2008, Galassi et al., 2006). Approximately, 80% of CADs can be prevented through healthy life style and reducing associated risk factors (Mozaffarian et al., 2014). Consequently, nowadays, herbal medicine, one of the main therapeutic approaches of complementary and alternative medicine, has attracted considerable attention by individuals with CVD for its unique advantages in preventing and treating diseases (Craig, 1999, Keli et al., 1996, Tachjian et al., 2010, Xiong et al., 2014, Zhang and Z.Wang, 2009). Many of the active phytochemicals in herbs, especially polyphenolic compounds, possess hypolipidemic, antioxidant and antiplatelet properties, that could improve the risk factors of CAD (Ahmad and Beg, 2013, C et al., 1996, Peluso, 2006, Quinones et al., 2013). Gundelia tournefortii L. (GT) from the Asteraceae (Compositae) family, locally known as "Kangar" in Iran, is an edible spiny, thistle-like plant native to Iran, Turkey, Azerbaijan, Egypt, Cyprus, Jordan and other areas of Western Asia (C¸ oruh N et al., 2007, MATTHÄUS1 B and M.M., 2011). Common names of GT are Galgal, Tumbleweed, Tumble Thistle, Akkub or Akoub. In the Middle East, the stalk of the plant has been widely used in traditional medicine as a hepatoprotective and blood purifier as well as a potential remedy for diabetes, chest pain and heart stroke (Jamshidzadeh et al., 2005, Halabi S et al., 2005, Hamdan and Afifi, 2004). GT is rich in phenolic compounds, especially flavonoids, including caffeoylquinic acid derivatives (cynarin and chlorogenic acid), quercetin, gallic acid, and other components such as limonene, zingiberene and saponins which are responsible for the biological activity of the plant (Asadi-Samani et al., 2013, Haghi G et al., 2011, Hildebert W et al., 1984, Nakatani et al., 2000, Yamanaka et al., 1997). As potential antioxidants, the polyphenols of this plant may play a substantial role in the prevention of various pathological conditions, especially cardiovascular diseases and cancer (Asgary S et al., 2009, C¸ oruh N et al., 2007, Haghi G et al., 2011, Halliwell, 1994). Some studies have suggested that the anti-atherosclerotic properties of GT are a result of its hypolipidemic, anticoagulant and antioxidant properties (Asgary S et al., 2009, Hammadi S Kh and J., 2004). Furthermore, some animal studies have demonstrated that GT could modulate lipid profile. The suggestion is that it may decrease total cholesterol and low density lipoprotein-cholesterol (LDL-c) (Asgary S et al., 2009, Azeez O. H and A.E., 2012). The plant has also displayed anti-inflammatory, analgesic and

antioxidant effects in both in vitro and in vivo studies(C¸ oruh N et al., 2007, Oryan Sh et al., 2011). Some animal studies have also shown that GT may regulate appetite and energy intake thus conferring a possible anti-obesity effect (Azeez O. H and A.E., 2012, de Melo et al., 2010, Hildebert W et al., 1984). To date, no clinical trials concerning the effects of G. tourneforti extract (GTE) in humans has been conducted. In view of the potential anti-atherosclerotic effects of GT, the present study was intended to investigate the possible effects of GTE consumption on lipid profile and total antioxidant capacity (TAC) in patients with CAD (Bunting et al.).

Materials and methods Preparation of the extract and placebo capsules The aerial parts of GT (Figure 1) were collected from mountainous areas around Urmia, Western Azerbaijan, Iran in May 2013 and its identity was confirmed by a panel of expert botanists at the Botany Department, Tabriz University, Tabriz, Iran. The plant specimen with the necessary field records was prepared and stored in the herbarium at Tabriz University. Thereafter, 170 kg of the fresh plant was dried in a shaded and ventilated place at room temperature. Dried plant material (aerial parts) were ground to a powder using a steel commercial blender. The powdered plant (9 Kg) was then macerated in 96% aqueous EtOH at room temperature for 72 h. The extract was filtered through filter paper (Whatman, No 1) and concentrated under a vacuum reduced pressure and low temperature (40°C) on a rotary evaporator (Laborata 4000; Heidolph, Germany). The extract yield obtained from the powdered extract was 38 mg/g. The extract was frozen at -80°C for one week. The whole freeze dried extract (350 gr) was then placed at room temperature and mixed with 350 gr of the excipient (microcrystalline cellulose and lactose). The whole extract powder (the mixture of extract and excipient) and placebo were filled into capsules with identical appearance using a handoperated capsule-filling machine to preserve the double blind condition. Each GTE capsule contained 250 mg of hydroalcoholic extract, 200 mg microcrystalline cellulose, 50 mg lactose and 4 mg magnesium stearate. Whereas, the placebo capsules contained 450 mg microcrystalline cellulose, 50 mg lactose and 4 mg magnesium stearate.

Subjects The study screened 60 potentially suitable individuals who were admitted to the heart hospital of Seyed-al-Shohada in Urmia, Iran and 45 men were enrolled. The inclusion criteria used were as follows: men* aged 40 to 80 years, angiographically CAD with more than 60% diameter stenosis of at least one of the major coronary vessels and BMI between 20 and 30 kg/m2. The exclusion criteria used were: triglyceride>500 mg/dl, any change in treatment one month before the expected change of medicinal plan during the study, clinical diagnosis of cardiomyopathy, myocardial infarction, valvular heart disease, dysrhythmia, heart failure, cancer, diabetes mellitus, chronic inflammatory disease, autoimmune disease, history of hypersensitivity to GT and current administration of antioxidant or vitamin supplements. *To address possible confounding factors only men were enrolled into the trial on the basis that it is evident from the current literature that in both pre and postmenapausal women significant changes, mostly attributed to alterations in serum levels of steroid hormones, may affect the atherogenic lipid profile and oxidative balance and subsequently the development of ischemic heart disease (Bittner, 2001; Mccrohon et al 1999). Furthermore the use of different levels of either hormone replacement therapy or foods high in phytosterols which is traditionally practised in the locality where the study was conducted was considered to be a further complication in this initial exploratory study. All the subjects gave written, informed consent prior to participation in the study and understood that they could withdraw at any time. Local research ethics committee of Tabriz University of Medical Sciences approved the study (Reference no: 92173). This study is registered at the Iranian Registry of Clinical Trials (IRCT registration number: IRCT2013102311288N6, at http://www.irct.ir/searchresult.php?keyword=&id=11288&field=&number=6&prt=5384&tot al=10&m=1). Study Design The current study was carried out using a double-blind, randomized, placebo-controlled, parallel design at Tabriz University of Medical Science, Tabriz, Iran from April to July, 2014. After obtaining the patients consent, they were randomly allocated to either the GTE (500 mg capsules/day, n=19) or placebo groups (n=19) using a computer-generated random number table. All researchers, participants and staff of patients' recruitment center were ‘blinded’ to treatment assignment. The daily dosage was equivalent to about 6 g of fresh aerial parts of GT as used in traditional medicine. The patients were asked not to change their routine medical treatments during the study and their dietary habits and life style were to remain the

same for the whole duration of the study. None of the subjects started any new medications for the period of the study. The participants were requested to report if they experienced any adverse effects. Anthropometric measurements (weight and height) were recorded and BMI was calculated. Patients’ dietary intake was measured using a 24-h recall questionnaire by a nutritionist before and after the study intervention. Foods were converted into nutrients with the software Nut4 version 1. The participants also filled out questionnaires regarding their demographic characteristics plus medical and smoking history. Physical activity level was assessed using the International Physical Activity Questionnaire for 7 days (VasheghaniFarahani et al., 2011). Blood samples were collected by venipuncture immediately before and after 8 weeks of treatment and directly spun at 3000 rpm for 10 min at 4°C; the serum was removed and stored at -80°C prior to analysis for measurement of plasma concentrations of the total antioxidant capacity (TAC), serum total cholesterol, triglyceride, high density lipoprotein-cholesterol (HDL-c) and LDL-c. TAC was assessed using enzyme-linked immunosorbent assays (Human TAC ELISA Kit, LDN Labor Diagnostika Nord GmbH & Co. KG, Germany). Serum total cholesterol, triglyceride and HDL-c were measured by enzymatic-colorimetric assays using commercially available kits (Randox Laboratories, Antrim, UK); Friedewald formula was used to calculate the serum LDL-c concentrations(Friedewald et al., 1972).

Statistical analysis Normality of data was checked using the Kolmogorov-Smirnov Test. Continuous variables were represented as mean and standard deviation or frequencies and percentages for normally distributed and categorical variables, respectively. Pearson’s and Spearman’s correlation tests were used to explore the relationship between BMI, demographic variables, lipid profile and TAC where appropriate. Paired sample t-test and Wilcoxon rank-sum test were used to compare means between two groups where appropriate. All analyses were performed using SPSS, ver 13.5.

Results The flow of volunteers through each stage of the trial is detailed in Figure 2 following the Consort recommendations for reporting trials statement (Moher et al., 2001). Of the 45 subjects randomized into the trial, three (one in the GTE group due to myocardial infarction and two in the placebo group due to changes in medication regimen) did not receive the intervention. Four (two in the GTE group and two in the placebo group) did not continue the

intervention in the middle of the study, because of changes in their medication regimen. Finally, 38 volunteers completed the eight weeks study protocol. Demographic characteristics were summarized in Table 1. Volunteers were over 50 years old in both the groups (60±10.8). The majority of the volunteers reported light amounts of physical activity (Table 1). Individual characteristics did not differ between the experimental and placebo groups. There was a statistically significant relationship between triglyceride and BMI (p=0.008, r=0.42). There was a reverse correlation between BMI and HDL-c (p=0.01, r=-0.42) and between LDL-c and HDL-c (p=0.01, r=-0.46). The calorie intake of patients was statistically significant before and after intervention in GTE group (p=0.04), but it was not significant in the placebo group (p=0.12). Among the three macronutrients, carbohydrate intake decreased after intervention in the GTE group (p=0.03) (Table 2). There was also a significant decrease in the BMI of the GTE group from 26.5±3.6 kg/m2 at baseline to 25.9±3.6 kg/m2 at the end of the trial (p=0.005). BMI decreased non-significantly in the placebo group from 24.7±3.5 kg/m2 at baseline to 24.4±3.9 kg/m2 at the end of the trial (p=0.998) (Table3). Figure 3 shows the changes in lipid profile percentage. There was a significant difference in the changes of total cholesterol in the two groups after the intervention (p=0.02). The total cholesterol concentration decreased in the GTE group from 151±23.8 mg/dl at baseline to 131.1±25.9 mg/dl at the end of the trial. In contrast, there was a slight increase in the serum cholesterol of the placebo group from 133.5±22 mg/dl at baseline to 141.4±22.4 mg/dl at the end of the trial. The mean value of LDL-c level remarkably changed in the two groups after the intervention (p=0.002). LDL-c decreased in the GTE group from 86±26 mg/dl at baseline to 60.58±29.9 mg/dl at the end of the trial, whereas it increased in the placebo group from 66.5±20.3 mg/dl at baseline to 73±25.1 mg/dl. No further statistically significant differences were observed for HDL-c or triglyceride in the two groups. However, TAC significantly increased in both groups after the intervention (Table 4), and there were no adverse effects reported.

Discussion To the best of the authors’ knowledge, this is the first study that examines the effects of GTE on lipid profile and TAC in humans. The main findings of this study were a considerable reduction in the total cholesterol, LDL-c and BMI in patients with CAD after an 8 week intervention period. HDL-c also increased by 2% in the GTE group more than placebo group. Triglyceride concentration increased in the placebo group by 17% more than the GTE group.

These results indicated that in this trial GTE was able to suppress some major risk factors of CAD, especially the dyslipidemia and high BMI. Many researchers believe that the properties of GT are similar to artichoke (H., 1999). The hypolipidemic and antioxidant properties of artichoke have been known for many years (Wo´jcicki J et al., 1981). In a study by Rafe Bundy et al., artichoke leaf extract decreased the total cholesterol level by 4.2% after 12 weeks with no inhibiting effect on LDL-c, HDL-c or triglyceride levels (Rafe Bundy et al., 2008). (Rafe Bundy et al., 2008). In another study, after 6 weeks supplementation with artichoke juice or placebo, a remarkable reduction in the concentrations of total cholesterol and LDL-c was observed in both artichoke and placebo groups and levels of triglyceride were increased by 5.7 percent (table 5). (Graziana Lupattelli et al., 2004). Interestingly, the degree of the changes in total plasma cholesterol, LDL-c and HDL-c values in the current study was greater than those previously reported for artichoke (in regard to the dose and duration of the intervention) (Table 5). Key compounds of GTE are mono and dicaffeoylquinic acids, particularly cynarin and chlorogenic acid which are potentially responsible for the antioxidant and hypocholestrolemic effects of both GTE and artichoke (Asadi-Samani et al., 2013, Haghi G et al., 2011, Nakatani et al., 2000). The findings in this study concurred with those of Asgary et al. in an animal model, indicating that GT decreased the level of LDL-c and total cholesterol and enhanced HDL-c in rabbits(Asgary S et al., 2009). Azeez et al. also showed a remarkable reduction in body weight, triglyceride and total cholesterol level in mice treated with GTE. They suggested that these effects were due to the flavonoid compounds of GTE through the inhibition of lipoprotein oxidation and increase in LDL receptor activity and/or saponin contents of GTE(Azeez O. H and A.E., 2012). Hildebert and colleagues identified seven saponins from GT by the use of droplet countercurrent chromatography. They indicated that the major saponin contents of GT were glycosylated derivatives of oleanolic acid (OA) (Hildebert W et al., 1984). The underlining mechanism by which GTE induces hypolipidemic effects was not investigated. Based on the current literature however, this might be attributed to its flavonoid contents and the saponins which are found in the plant (Hammadi S Kh and J., 2004, Hildebert W et al., 1984). Other studies demonstrated that the cynarin and chlorogenic acid content of GTE could inhibit hydroxymethylglutaryl-CoA-reductase (HMG CoA reductase) and may cause a reduction in de novo cholesterol synthesis (K., 1997, Mills S. and K, 1999). The gallic acid content of GTE may be an effective element in preventing cardiac dysfunctions (Dhalla et al., 1985, Patel and Goyal, 2011). All things considered, it appears

that herbs with gallic acid were the strongest inhibitors of lipogenesis, especially cholesterol synthesis (Chi-Hua Lu and Hwang, 2008, Liu et al., 2001). The hydrolysis of saponin to sapogenin in the gastrointestinal tract could stimulate secretion of bile acids by the liver. Saponin decreases absorption of cholesterol in the intestine and may stimulate the liver to convert cholesterol to bile acids(Petit P et al., 1995, Sauvaire Y et al., 1996). In general, investigations have revealed that plants belonging to the Asteraceae family exert a true choleretic action when they were tested in the same animal model(García MD et al., 1990). The current study revealed a greater reduction in calorie intake in the GTE group as compared to the placebo group (a reduction of 763 Kcal in GTE group compared to 177 Kcal in placebo). It is suggested that glycosylated derivatives of oleanolic acid (a pentacyclic triterpene that occurs widely in many plants as the free acid or the aglycone for many saponins) may contribute in weight loss by mobilization of visceral fat deposits (de Melo et al., 2010, Hildebert W et al., 1984). The inhibition of alpha-amylase activity may hinder the digestion of carbohydrates and this may in part account for the weight loss observed in OAtreated mice (H. Ali et al., 2006). In addition, OA decreases ghrelin and enhances leptin secretions which results in down regulation of appetite (de Melo et al., 2010). It is generally accepted that the oxidation of LDL-c by reactive oxygen species accelerates the initiation and progression of atherosclerosis (Zapolska-Downar et al., 2002). Ox-LDL is a potent stimulator of oxidative stress that causes dysfunction of endothelial cells (Selwyn et al., 1997, Cominacini et al., 2000). In this study however no effect was demonstrated for GTE on TAC. Conversely, several previous studies have indicated high antioxidant capacity of GTE. In a study by Sekeroglu et al., the seed of GT represented notable radical scavenging effect against 2, 2-diphenyl-1 picrylhydrazyl (DPPH) (Sekeroglu N et al., 2012). Coruh et al. found that methanol extracts of GT had remarkable antioxidant capacity as compared to αtocopherol by the inhibition of glutathione-S-transferase activity (which is important for the detoxification of by-products of lipid peroxidation or DNA hydroperoxides in biological systems). They also reported that DPPH radical scavenging activity and inhibition percent of lipid peroxidation by seeds were much higher than the aerial parts of GTE. In addition, total phenolic contents of the seed extract were also much higher than the aerial parts(C¸ oruh N et al., 2007). The contradiction between the findings of the current study with the reports of Coruh et al. could be attributed to the fact that the aerial parts of GT have less antioxidant capacity than the seeds. In addition, the doses used in these studies (in vitro and animal model) were remarkably higher than the current study (C¸ oruh N et al., 2007, Azeez O. H and A.E., 2012, Sekeroglu N et al., 2012). No serious adverse events were documented in the

trial and the overall judgment of tolerability was given as 'good' or 'excellent' in 98.5% of cases.

Limitations Our study had some limitations. Firstly, because there were no previous studies on human subjects the dose used was that used in traditional medicine therefore it is possible that GTE did not have influence on TAC due to the low doses of the extract used in the trial. Secondly, to address medical ethics, the authors did not recommend any changes in routine medications of the study participants which could have influenced lipid profile and TAC. However, to minimize this effect, the subjects were randomly matched for therapeutic regimens within the two groups.

Conclusion In conclusion, GT was able to improve the lipid profile, particularly total cholesterol and LDL-c, in the study subjects with good tolerability and thus it may be used as an appropriate medicinal plant for modifying the risk factors attributed to CAD. In addition, it is suggested that GTE may be a beneficial adjunct therapy for the management of atherosclerosis in patients with CAD.

Conflict of interest All the authors declare no competing interests.

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Enrolment

Assessed for eligibility n =60

Did not meet inclusion criteria n =15

Analysis

Follow-up

Allocation

Randomized n =45

Allocated to intervention n =22 Did not receive intervention n =1

Myocardial infarction

Discontinued intervention n =2 Changes in medication regimen

Analyzed n =19

Allocated to intervention n =23 Did not receive intervention n =2 Changes in medication regimen

Discontinued intervention n =2 Death

Analyzed n =19

Fig 2. The flow of volunteers through each stage of the study, as based on recommendations

made in the CONSORT statement

Fig 3. changes percent of TC (A), LDL (B), HDL (C) and TG (D) concentration by GTE compared to placebo. Results are expressed as mean and SEM. TC: total cholesterol; LDL : low density lipoprotein; HDL: high density lipoprotein; TG: triglyceride; GTE: Gundelia tournefortii extract.

Table 1 Demographic characteristics of participants at baseline Mean(SD)

Mean(SD)

GTE (n=19)

Placebo (n=19)

Age (years)

57.5 (10.8)

62.6 (10.8)

Body mass index (kg/m2)

26.5 (3.6)

24.7(3.9)

Physical activity (n)

1.94 (1.7)

2.36 (2.3)

Hardly any

3

2

Light

10

12

Moderate

6

4

Great

0

1

N (%)

N (%)

Yes

11(61)

13(69)

No

8(39)

13(69)

8(45)

12(63)

Smoking history

hypertension

Table2 Comparison of dietary intake in the study groups at baseline and at the end of study. Variable

Energy (kcal/day)

Carbohydrate (g/day)

Protein (g/day)

Fat (g/day

a

Intervention(n=19)

Placebo (n=19)

P-valuea

Initial

3120±341b

2903±280

0.37

End

2357±131

2726±121

0.12

P-valuec

0.04

0.42

Initial

320±82

362±91

0.54

End

260±61

320±74

0.34

P-valuec

0.03

0.19

Initial

134±23

143±41

0.31

End

111±14

135±32

0.19

P-valuec

0.21

0.51

Initial

144±61

97±24

0.21

End

97±31

102±34

0.44

P-valuec

0.08

0.90

Independent t-test; p<0.05 considered significant

b c

Period

Mean±SD

Paired t-test; p<0.05 considered significant

Table3 Anthropometric indices in two groups at the baseline and at the end of study. variable

Weight (kg)

period

Intervention

Placebo

p-valuea

Initial

79.7±10.6b

71.6±15

0.06

End

77±10.11

71.5±14

0.22

P-valuec

0.006

0.973

160±6.4

159±8.6

0.12

Initial

26.5±3.6

24.7±3.5

0.13

End

25.6±3.6

24.4±3.9

0.45

P-valuec

0.005

0.998

Height (cm)

BMI (kg/m2)

a

Independent t-test; p<0.05 considered significant

b c

Mean±SD

Paired t-test; p<0.05 considered significant

Table4 Comparisons of biochemical parameters before and after the intake of GTE and Placebo. variable

GTE(n=19)

Placebo(n=19)

Before

After

p

Before

After

p

151±23.8

131.1±25.9

0.04

133.5±22

141.4±22.4

0.30

LDL-c (mg/dl)

86±26

60.58±29.9

0.001

66.5±20.3

73±25.1

0.40

HDL-c (mg/dl)

42.6±6.1

50.1±15

0.06

46.1±20

49.8±10.1

0.33

Triglycerides

128.8±33.9

138.4±48.9

0.79

100.8±42.5

116.1±33.03

0.94

3.2±0.8

0.03

2.4±1.0

3.1±0.7

0.04

Total cholesterol (mg/dl)

(mg/dl) TAC(mmol/l)

2.5±0.9

LDL-c: low-density lipoprotein cholesterol; HDL-c: high-density lipoprotein cholesterol; TAC: total antioxidant capacity

Table 5 Comparison of the effects of Gundelia Tournefortii extract (current study) with Artichoke extract on the lipid profile TC¶ Studies

LDL-c¶

HDL-c¶

TG¶

Daily dosage/Duration Subjects

EXP*

PLB**

EXP*

PLB**

EXP*

PLB**

EXP*

PLB**

(weeks) Current study

38 patients with CAD

Englisch, et al;

143 patients with

2000

hyperlipoproteinemia

Bundy, et al; 2008

75 healthy adults

Fallah Huseini, et

72 patients with type 2

al; 2012

diabetes

Lupattelli, et al; 2004

18 hyperlipemic patients

250 mg (8 )

-10.8

+8.4

-30.2

+22.4

+19.9

+17.3

+7.9

+1.1

450 mg (6)

-18.5

-8.6

-22.9

-6.3

NS

NS

NS

NS

320 mg(12 )

-4.2

+1.9

-5.1

+1.7

-0.6

+0.6

-5.3

-1.8

120 mg (8 )

-6.7

+2.1

-6.3

+4.4

-6.6

-4.4

-17.9

-7.6

20 ml (6)

-6.5

-6.7

-8

-8.8

-7.1

0

+5.7

-7.3

¶ expressed as percent of changes. * and ** represents experimental and placebo groups, respectively. NS: percent of changes was not statistically significant (exact values were not available).

23