Med. J. Cairo Univ., Vol. 80, No. 2, March: 101-113, 2012 www.medicaljournalofcairouniversity.com
Beneficial Health Effects of Fennel Seeds (Shamar) on Male Rats
Feeding High Fat-Diet
AMR A. REZQ, Ph.D.
The Department of Nutrition and Food Science, Faculty of Home Economics, Helwan University, Cairo, Egypt
Abstract and low density lipoprotein cholesterol, and decrease the risk of chronic heart diseases by increasing level of HDL-C as Fennel has been known since antiquity as a medicinal well as enhancing activities of antioxidant enzymes. and aromatic herb, it commonly used in household remedy for various medicinal purposes. The present study was con- Key Words: Fennel – Hyperlipidemia – Hypercholestermia – ducted to investigate the effect of beneficial health effects of Liver functions – Antioxidant system. fennel seeds on feeding rats with high fat-diet. Histopatho- logical changes of aorta, heart and liver were examined. Thirty Introduction five male albino rats of Sprague-Dawley strain weighing
200±5g were used. Animals were divided into five groups of HYPERLIPIDEMIA is a heterogeneous disorder seven rats each: group (1) fed on the basal diet and kept as
a negative control group; group (2) fed on high fat–diet and involving multiple etiologies. It is characterized kept as positive control group; groups (3), (4) and (5) fed on by the elevated in serum levels of free fatty acids, high fat diets supplemented with three different levels of triglycerides (TG), total lipid (TL), total cholesterol fennel seeds (5, 10 and 15%, respectively. The present results (TC), low-density lipoprotein-cholesterol (LDL- revealed that rats fed on high fat-diet only (positive control C) and Apolipoprotein B, and reduced serum high- group) had significant (at p<0.05) increase in serum TL, TG, TC, LDL-C, VLDL-C, AST, ALT, ALP and MDA concentra- density lipoprotein cholesterol (HDL-C) concen- tions, and significant decrease in serum HDL-C level as well tration [1] . as significant decrease in HDL-C/LDL-C ratio value and serum activity of CAT, GPX and SOD enzymes as compared Hyperlipidemia contributes significantly in the to rats fed on basal diet only (negative control group). High development of atherosclerosis and coronary heart fat-diet supplemented with the three different levels of fennel diseases. Atherosclerosis is the most common cause seeds significantly improved serum levels of TL, TG, TC,
LDL-C, VLDL-C, AST, ALT, ALP and MDA, and significant of mortality and morbidity worldwide [2] . High raise in serum HDL-C level, values of HDL-C/LDL-C ratio cholesterol diet leading to hyperlipidemia is re- and improve activities of CAT, GPX and SOD enzymes garded as an important factor in the development compared to the positive control group. Histopathological investigation showed vaculations of tunica media and narrow- of ischemic heart disease. Ischemic stress of the
ing in the lumen of aorta sections and congestion of cardiac heart is a major cause of mortality in civilized blood vessel as well as fatty change of hepatocytes in positive societies [3] . Although several factors, such as diet control rats. Vaculations of tunica media in aorta sections and high in saturated fats and cholesterol, age, family fatty changes of hepatocytes were showed in rats fed high history, hypertension and life style play a significant fat-diet supplemented with 5% of fennel seeds. Slight thick- role in causing heart failure, the high levels of ening in the wall of aorta sections was showed in rats treated with 10% fennel seeds, whereas, other sections showed ap- cholesterol particularly TC, TG and LDL-C is parent normal histological structure. Its liver sections had mainly responsible for the onset of cardiovascular small vacuoles in the cytoplasm hepatocytes. Liver sections diseases [2] . of treated rats with 15% fennel seeds showed small vacuoles in the cytoplasm of some hepatocytes and other sections revealed apparent normal hepatocytes. There were no histo- The use of medicinal plants for health started
logical changes in heart sections of all treated rats with fennel from thousands of years and still a part of the seeds and in aorta of rats treated with 15% fennel seeds. In medical practice in Egypt and other developed
conclusion, the present study revealed that fennel seeds countries. Foeniculum vulgare is an annual, biennial improve dyslipidaemia by improving lipid profile, cholesterol or perennial plant, depending on the variety and it
is a well-known umbelliferous plant. The leaves, Correspondence to: Dr. AMR A. REZQ, The Department of
Nutrition and Food Science, Faculty of Home Economics, Helwan stalk and seeds are edible part. Fennel is the ripe
University, Cairo, Egypt fruit known as seed of Foeniculum Vulgare [4] . It
101 102 Beneficial Health Effects of Fennel Seeds (Shamar) on Male Rats
is a commonly used in household remedy for var- The Gamma Trade Company for Pharmaceutical
ious medicinal purposes [5] . Fennel seed has been and Chemicals, Dokki, Egypt.
known since antiquity as a medicinal and aromatic Preparation of fennel seeds: Dried fennel seeds herb, commonly used to flavor breads, fishes, (shamar) were washed with tap water to remove salads and cheeses [6] . Some people use fennel as possible potential dust. Afterwards, it was dried a diuretic, and it may be an effective diuretic and by cotton cloth to remove the excess liquid prior a potential drug for treatment of hypertension [7] . to drying. Drying was achieved at room temperature It can be add into syrup to treat babies with colic for 48 hr. Then a grinder mill and sieves were used [8] . to obtain a powder particle size of less than 0.2mm.
Fennel seeds are rich in carbohydrates, moisture, Preparation of basal diets: The basal diet (AIN- and protein and fat [9] . Its mineral contents are 93M) was prepared according to Reeves et al. [24] . calcium, phosphorous, iron, sodium and potassium. Diet was formulated to meet recommended nutri- Vitamins content are thiamine, riboflavin, niacin ents levels for rats. and C [10] . The major fatty acid components of
fennel seeds are oleic acid and linoleic acid. Fennel Experimental design: seeds are high in isoleucine and histidine [9] . The The experiment was conducted on thirty five seed oil yield varies according to variety and origin male rats weighing approximately 200 ±5g for 4 and the highest concentration of fennel oil ranging weeks. The animals were housed in healthy condi- from 2-7%. Fennel volatile oil is a mixture of tion at room temperature (21-23ºC), with 40-60% different chemicals and the main ingredients are humidity, exposed to a 12: 12-h light-dark cycle anethole, fenchone and estragole [4] . and fed on the basal diet and water was provided
Recently, fennel seeds were found to have a ad libitum for one week before starting the exper-
hypotensive effect [11] , antispasmodic activities imental for acclimatization. After acclimatization [12] , antihirsutism [13] , hepatoprotective [14] , anti- period rats were divided into five groups of seven
inflammatory [15] , antidementia [16] , possess pain rats each: group (1) fed on the basal diet and kept
reliever in primary dysmenorrhoea [17] , antiplatelet as a negative control group (normal rats); the
and antithrombotic [18] , immunomodulatory [19] , remaining four groups fed high fat containing-diet.
protective effect against ethanol induced gastric Group (2) kept as a positive control group; groups
mucosal lesions [20] , anticancer [21] , potential in (3), (4) and (5) fed on high fat diets supplemented
the treatment of glaucoma [22] and antioxidant [23] . with the three different levels of fennel seeds (5,
10 and 15%, respectively). Hyperlipidemia in rats
The current study was aimed to investigate the was done according to the method described by beneficial health effects of fennel seeds (Foenicu- Balkan et al. [25] . In briefly, basal diet was formu-
lum vulgare) administration on hyperlipidemic rats lated with 1% cholesterol, 2% sheep fat and 0.5%
feed on high fat-diet. Histopathological changes cholic acid to enhance the enteral absorption of
of aorta, heart and liver were examined. lipids.
Material and Methods At the end of the experimental period, diets
were withheld from experimental rats for 12-h and Fennel seeds (foeniculum vulgare): Fennel then rats were sacrificed. Blood samples were seeds were obtained from Haraz market for herbs collected from the portal vein into dry clean cen- and medicinal plants market, Cairo, Egypt. trifuge tubes. For serum separation, blood samples
Rats and diet: Thirty five male albino rats of were left at room temperature to get clot, and then
± Sprague-Dawley strain weighing 200 5g were centrifuged for 15 minutes at 3000 rpm. Serum
obtained from the Laboratory Animal Colony, was carefully aspired using a needle and transfers
Ministry of Health and Population, Helwan, Egypt. into dry clean test tubes and kept frozen at-10ºC Basal diet constituents were purchased from El- until chemical analysis. Gomhorya Company for Pharmaceutical and Chem- Aorta and organs such as heart and liver were ical, Cairo, Egypt. removed and washed with saline solution, dried,
Kits: Kits for biochemical analysis of serum and kept in formalin solution (10%) for histopatho-
TL, TG, TC, HDL-C, aspartate aminotransferase logical examination.
(AST), alanine aminotransferase (ALT), alkaline
Biochemical analysis: phosphatase (ALP), malondialdehyde (MDA),
catalase (CAT), glutathione peroxidase (GPX) and Lipid profile and lipoprotein cholesterol assay:
superoxide dismutase (SOD) were purchased from Serum TL concentration was determined colori- Amr A. Rezq 103
metric using spectrophotometer apparatus adjust Results
at 520nm as described by kit instructions (Randox Serum total lipids, triglycerides and total cho- Co., Ireland). TG, TC and HDL-C concentrations were determined using enzymatic methods as de- lesterol concentrations: Recorded data in Table (1) illustrated that feeding animal with high fat scribed in the instructions provided with the kits diet (positive control group) produced a significant (Analyticon® Biotechnologies AG, Germany). The (p<0.05) elevation in serum TL concentration absorbance of the testes samples were read using ± (442.43 0.37mg/dL), as well as significant increase spectrophotometer adjusted at 546nm for TG and ± in TG and TC concentrations (135.43 0.30 and TC, and 500nm for HDL-C. ± 99.14 0.26mg/dL, respectively) as compared to Low density lipoprotein cholesterol concentra- the feeding animal with normal basal diet only ± ± (371.29 0.42, 115.14 0.51 and 58.14±0.26mg/dL, tion was calculated by using formula of Friedwald respectively). Supplemented high fat diet with et al. [26] . Then ratio of high density lipoprotein fennel seeds at different levels reduced significantly cholesterol to low density lipoprotein cholesterol (p<0.05) serum TL, TG and TC levels as compared (HDL-C/LDL-C) was measured. Very low density to feeding animal with high fat diet only. lipoprotein cholesterol (VLDL-C) was calculated using the following equation: Serum LDL, HDL and VLDL-cholesterol con-
VLDL-c (mg/dL) = TG/5 centrations: Data in Table (2) revealed that serum LDL-C and VLDL-C levels were higher signifi- Liver functions assay: Serum AST, ALT and ± ± cantly at p<0.05 (59.04 0.18 and 27.06 0.10mg/ ALP activities were determined using colorimetric dL, respectively), while HDL-C level was lower methods as described in the kits instruction (Dia- significantly (13.00±0.31mg/dL) in positive control mond Co, Hannover, Germany). The absorption ± rats compared with negative control rats (11.11 of the test samples were read at 505nm for AST 0. 11, 23.03±0. 1 0mg/dL, 24.00±0.3 1 mg/dL, respec- and ALT and at 510nm for ALP. tively). High fat diets supplemented with fennel
seeds at different levels reduced significantly serum Malondialdehyde assay: Serum MDA concen- levels of LDL-C and VLDL-C, and raised signifi- tration as indicator of lipid peroxidation was de- cantly serum HDL-C level compared with feeding termined. The principle of the methods is spectro- rats with high fat diet. photometric measurements of the color produced by the reaction of thiobarbituric acid (TBA) with HDL/LDL-C ratio: As shown in Fig. (1) results MDA. The concentration of MDA was then calcu- demonstrated that mean ±SE for value of HDL- µ lated and expressed as moles/dl [27] . C/LDL-C ratio was lower significantly ( p<0.05) ± in positive control rats (0.22 0.06) compared with Antioxidant defense system assays: Activity of ± the negative control rats (2.16 0.04). In contrast, CAT, GPX, SOD enzymes were determined by feeding rats with high fat-diet supplemented with Autoanalyzer (Roche-Hitachi, Japan) using com- different levels of fennel seeds induced significantly mercial kits according to the methods described ± higher in values of HDL/LDL-C ratio (0.61 0.02, by Sinha, [28] , Hissin and Hiff, [29] ; Kakkor et al. ± ± 0.92 0.02 and 1.33 0.05, respectively) compared [30] respectively. to positive control rats.
Histopathological examination: Aorta, heart Liver functions: Serum AST, ALT and ALP and liver of the scarified rats were taken and im- concentrations as indicator of liver function in rats
mersed in 10% formalin solution. The fixed spec- are shown in Table (3). Data showed that positive
imens were then trimmed, washed and dehydrated control group had significant (p<0.05) increase in
in ascending grades of alcohol. Specimens were serum AST, ALT and ALP levels (26.86 ±0.51, then cleared in xylol, embedded in paraffin, sec- 21.86±0.26 and 50.29±0.18U/L, respectively) com-
± tioned at 4-6 microns thickness, and stained with pared with the negative control group (16.14 0.40,
Heamtoxylin and Eosin stain for histopathological 13.29±0.29 and 37.14±0.34U/L, respectively).
[31] examination as described by Carleton, . Feeding high fat diet supplemented with 5, 10 and
15% of fennel seeds induced significant ( p<0.05) Statistical analysis: Results were expressed as decrease in serum AST, ALT and ALP levels com- mean±SE. All data from the experiment were ex- pared to the positive control group. amined statistically by one-way analysis of variance
with computerized SPSS package program (SPSS Serum malondialdehyde concentration and
6.00 software for Windows) by ANOVA test. A p- activity of catalase enzyme: Tabulated results as
value <0.05 was considered statistically significant. shown in Table (4) revealed that positive control 104 Beneficial Health Effects of Fennel Seeds (Shamar) on Male Rats
rats had significant (p<0.05) increase in serum high fat diet supplemented with the three different ± µ MDA level (2.79 0.003 mol/dL) and significant levels of fennel seeds was detected as showed in ± decrease in the activity of CAT enzyme (42.19 Fig. (6). However, congestion of cardiac blood µ 0.27 mol/dL) compared with the negative control vessel and hyalinosis of its wall was showed in ± µ rats (1.25 ±0.002 and 68.56 0.49 mol/dL). How- rats from positive control group (Fig. 7).
ever, feeding rats with high fat-diet supplemented Liver: Liver sections of rats from negative with 5%, 10% and 15% of fennel seeds significantly ± ± control rats revealed normal histological structure reduced serum MDA (1.68 0.003, 1.48 0.004 and 1.41 ±0.004µmol/dL, respectively) levels and sig- of hepatic lobule as shown in Fig. (8). Liver sections of rats from positive control rats revealed fatty nificant increase activity of CAT enzyme compared change of hepatocytes and congestion of hepatic with the positive control rats. sinusoid, vacuolization of hepatocytes and necrosis
Activity of GPX and SOD enzymes: Recorded of sporadic hepatocytes as shown in Figs. (9,10,
results in Table (5) demonstrated that the positive respectively). Treated rats with 5% fennel seeds
control rats fed on high fat-diet only had significant revealed fatty change of hepatocytes as shown in
Fig. (11). Examined liver sections of hyperlipidemic (p<0.05) decrease in the activity of GPX enzyme ± rats treated with 10% fennel seeds revealed only (8.09 0.16mmol/dL) compared with the negative
± small vacuoles in the cytoplasm of hepatocytes as control rats fed on the basal normal diet (18.67 0.16 mmol/dL). Feeding rats with high fat-diet supple- shown Fig. (11). Meanwhile, liver sections of treated rats with 15% fennel seeds showed small mented with fennel seeds at different levels (5, 10 vacuoles in the cytoplasm of some hepatocytes as and 15%) increased significantly activity of GPX ± ± ± shown in Fig. (12), whereas, other sections revealed enzyme (9.28 0.03, 10.74 0.04 and 15.65 0.16 apparent normal hepatocytes. mmol/dL, respectively) compared with the positive
control rats. Table (1): Serum TL, TG and TC concentrations in hyperlip- With regard to the activity of SOD enzyme in idemic rats. serum of rats, tabulated results revealed that positive ± control rats had significant (p<0.05) decrease in Parameters as Mean SE ± Groups serum activity of SOD (55.95 0.17U/dL) enzyme TL (mg/dL) TG (mg/dL) TC (mg/dL) compared with the negative control rats (95.30 ±0.14 ± e Negative group 371.29 ±0.42e 115.14 0.51 58.14±0.26e U/dL). Feeding supplemented diets with the three ± ± ± different levels of fennel seeds increased signifi- Positive group 442.43 0.37a 135.43 0.30a 99.14 0.26a ± cantly (p<0.05) the serum activity of SOD (68.98 5% fennel 399.29±0.23b 129.29±0.42b 72.57±0.20b ± ± 0.17, 75.99 0.04, 87.88 0.04U/dL, respectively) ± c ± c ± c 10% fennel 388.43 0.43 122.15 0.40 66.14 0.26
enzyme compared to the positive control rats 15% fennel 375.86±0.26d 118.29±0.29d 61.71 ±0.15d (55.95±0.17U/dL).
A uses harmonic mean sample size = 7 rats.
Data represented as Mean ±SE. Histopathological examination: Means with different superscript letters are significantly different at Aorta: Fig.s (2-5) showed histopathological p<0.05.
structure of aorta sections in experimental animals.
Normal histological structure was showed in normal rats fed on normal basal diet (Fig. 2). However, Table (2): Serum LDL-C, HDL-C and VLDL-C concentrations vaculations of tunica media as well as narrowing in hyperlipidemic rats. in the lumen was showed in rats fed on high fat- ± Parameters as Mean SE diet (Fig. 3). Aorta sections of feeding rats with Groups LDL-C HDL-C VLDL-C high fat diet supplemented with 5% fennel seeds
(mg/dL) (mg/dL) (mg/dL) revealed vaculations of tunica media as showed in
± a Fig. (4). However, slight thickening in the wall Negative group 11.11 ±0.11 e 24.00 0.31 23.03±0.10e was showed in aorta sections of feeding rats on e Positive group 59.04±0.18a 13.00±0.3 1 27.06±0.10a high fat diet supplemented with 10% fennel seeds d ± b 5% fennel 28.80±0.16b 18.00±0.31 25.86 0. 1 0 (Fig. 5), whereas, other sections revealed apparent ± c ± c ± c 10% fennel 21.71 0.19 19.86 0.26 24.43 0.10 normal histological structure. Normal histological
15% fennel 17.20±0.33d 21.86±0.34b 23.66±0.10d structure of aorta was showed in feeding rats with high fat diet supplemented with 15% fennel seeds. A uses harmonic mean sample size = 7 rats.
Data represented as Mean ±SE.
Heart: Normal histological pattern of heart Means with different superscript letters are significantly different at tissue of negative control rats and feeding rats with p<0.05. Amr A. Rezq 105
Table (3): Serum AST, ALT and ALP concentrations in hyper-
lipidemic rats.
Parameters
Groups
AST (U/L) ALT (U/L) ALP (U/L) ± c Negative group 16.14±0.40d 13.29±0.29e 37.14 0.34
Positive group 26.86±0.51 a 21.86±0.26a 50.29±0.18a ± b 5% fennel 23.00±0.53b 17.57±0.20b 38.43 0.20 ± c ± c ± c 10% fennel 19.71 0.57 15.71 0.29 37.43 0.37
15% fennel 17.14±0.40d 14.43±0.20d 36.00±0.31 d
A uses harmonic mean sample size = 7 rats. ± Data represented as Mean SE.
Means with different superscript letters are significantly different at
p<0.05.
Table (4): Serum MDA concentration and activity of CAT Fig. (2): Aorta of rat from negative control group showing no enzyme in hyperlipidemic rats. histopathological changes (H & E x 400).
Parameters
Groups µ MDA ( mol/dL) CAT (mmol/dL)
Negative group 1.25 ±0.002e 68.56 ±0.49a
Positive group 2.79 ±0.003 a 42.19 ±0.27e
5% fennel 1.68 ±0.003b 52.43 ±0.23 d ± c ± c 10% fennel 1.48 0.004 56.53 0.17
15% fennel 1.41 ±0.004d 63.04 ±0.23b
A uses harmonic mean sample size = 7 rats. ± Data represented as Mean SE.
Means with different superscript letters are significantly different at
p<0.05.
Table (5): Serum activity of GPX and SOD enzymes in
hyperlipidemic rats.
Parameters
Groups
GPX (mmol/dL) SOD (U/dL)
Fig. (3): Aorta of rat from positive control group showing Negative group 18.67±0.16a 95.30±0.14a vaculations of tunica media as well as narrowing in Positive group 8.09±0.16e 55.95±0.17e the lumen (H & E x 400). 5% fennel 9.28 ±0.03 d 68.98±0.17d
10% fennel 10.74±0.04c 75.99±0.04c
15% fennel 15.65±0.16b 87.88±0.04b
A uses harmonic mean sample size = 7 rats. ± Data represented as Mean SE.
Means with different superscript letters are significantly different at
p<0.05.
3
2.5 ± 2.16 0.04 2 ± 1.33 0.05
1.5
1 ± 0.92 0.02 HDL/LDL-C ratio ± 0.61 0.02 0.5 ± 0.22 0.06 0 –ve +ve 5% 10% 15% Fig. (4): Aorta of rat from hyperlipidemic rats treated with Groups of rats 5% fennel seeds showing vaculations of tunica media
Fig. (1): HDL/LDL-C ratio in hyperlipidemic rats. (H & E x 400). 106 Beneficial Health Effects of Fennel Seeds (Shamar) on Male Rats
Fig. (5): Aorta of rat from hyperlipidemic rats treated with Fig. (8): Liver of normal rats showing normal histological
10% fennel seeds showing slight thickening in the structure of hepatic lobule (H & E x 400).
wall (H & E x 400).
Fig. (6): Heart of rat from normal group showing no histo- Fig. (9): Liver of positive control rats showing fatty change
pathological change (H & E x 400). of hepatocytes (H & E x 400).
Fig. (7): Heart of positive control rats showing congestion of Fig. (10): Liver of positive control rats showing congestion
cardiac blood vessel and hyalinosis of its wall (H & of hepatic sinusoid, vacuolization of hepatocytes
E x 400). and necrosis of sporadic hepatocytes (H & E x 200). Amr A. Rezq 107
Discussion
Hyperlipidemia is known as a risk factor for
cardiovascular disease, especially atherosclerosis,
which is one of the major causes of premature
death globally and it is expected to be the most
important cause of mortality. It has been well
established that nutrition plays an important role in the etiology of hyperlipidemia and atheroscle-
rosis. The current study was aimed to investigate the beneficial health effects of fennel seeds (Foe-
niculum vulgare) administration on hyperlipidemic
rats feed on high fat-diet. Histopathological changes
of aorta, heart and liver were examined.
Fig. (11): Liver of treated rats 5% fennel seeds showing fatty Hyperlipidemia or dyslipidaemia is the presence
change of hepatocytes (H and E x 400). of elevated or abnormal levels of lipids and/or
lipoproteins in the blood. Lipid and lipoprotein
abnormalities are regarded as a highly modifiable
risk factor for cardiovascular disease due to the
influence of cholesterol, one of the most clinically
relevant lipid substances in atheroscterosis [32] .
Ample of evidence exists with respect to the fact
that HDL cholesterol is inversely related to total
body cholesterol and a reduction of plasma HDL cholesterol concentration may accelerate the de-
velopment of atherosclerosis leading to ischemic heart diseases, by impairing the clearing of choles-
terol from the arterial wall [33] . From the obtained
results it was observed that keeping the animal on
high fat-diet resulted in dyslipidemic changes as
illustrated by the significant increase in serum TL, TG, TC, LDL-C and VLDL-C, as well as a signif-
icant reduce in serum HDL-C level and value of Fig. (12): Liver of rat from hyperlipidemic group treated with HDL-C/LDL-C ratio compared to the rats on nor- 10% fennel seeds showing small vacuoles in the mal diet. These results were confirmed with histo- cytoplasm hepatocytes (H and E x 400). logical changes of feeding rats with high fat diet
only, which showed vaculations of tunica media
and narrowing in the lumen of aorta sections as
well as congestion of cardiac blood vessel and
hyalinosis of its wall. This result was in accordance
with Farmer and Gotto, [34] who reported that
plasma levels of LDL are associated with the
occurrence of atherosclerosis and impairment of
endothelial function of arteries in hyperlipidemic
patients. Parathasarathy et al. [35] reported that
hypercholesterolemia is one of the major risk factors for coronary artery disease and atheroscle- rosis. LDL-C plays a crucial role in the atherogen-
esis and it is the oxidative modification that imparts an atherogenecity to LDL. This result was con-
firmed by Szilvassy et al. [36] who indicated that
although hyperlipidemia increases oxidative stress
in the cardiovascular system, it renders the heart
and the vasculature more susceptible to stress. Fig. (13): Liver of rat from hyperlipidemic group treated with
15 % fennel seeds showing small vacuoles in the Recently, Ouwens et al. [37] identified that devel-
cytoplasm of some hepatocytes (H and E x 400). opment of hypercholestremia, which is one of the 108 Beneficial Health Effects of Fennel Seeds (Shamar) on Male Rats
risk factors for cardio vascular diseases is associated management of hyperlipidemic patients [44] . Anti-
with increased blood levels of TC, LDL-C and oxidative properties and radical scavenging activity
VLDL-C as well as lowered levels of HDL in rats may be the possible mechanisms by which fennel
fed on high fat-diet. Jain et al. [38] reported that ameliorated the TL, TC, TG and LDL-C [20] .
coronary heart disease is caused by the narrowing Flavonoids are reported to increase HDL-C con-
of the artery that supplies nutrients and oxygen to centration and decrease in LDL and VLDL levels
the heart. The main reason for this narrowing is in hypercholesteremic rats [45] . Furthermore, Gib-
atherosclerosis. Moreover, there is a relationship ney et al. [46] reported that hypolipedemic effect between the elevated in plasma lipids and the of fennel may be due to the high content of poly-
development of atherosclerotic plaques. Woo et unsaturated fatty acids from omega-6 and omega-
al. [39] showed that high fat-diet caused significantly 3 families that found in this plant and these com-
elevated in serum TG and TC levels, significantly pounds have strong biological properties in low
decreased in serum HDL-C compared to the con- concentrations.
trols rats. Liver function tests, which include liver en-
When high fat-diet was supplemented with the zymes, are groups of clinical biochemistry labora-
three different levels of fennel seeds (5, 10 and tory blood assays designed to give information
15%), the elevated levels of TL, TG, TC, LDL-C about the state of liver functions. The used serum
and VLDL-C condition has shown considerable liver chemistry test in the present study includes
decline which were significantly. This decline as serum AST, ALT and ALP. The activities of AST
effect by feeding fennel seeds was more detectable and ALT are cytosolic marker enzymes reflecting
with increasing the level of it. Moreover, serum hepatocellular necrosis as they are released into
level of HDL-C and mean values of HDL-C/LDL- the blood after cell membrane damage. Therefore,
C ratio were significant increase, compared to we used the activities of AST, ALT and ALP in the
feeding rats with high fat-diet only. Elevated level circulation as indicators of hepatic functions.
of HDL-C is considered as cardio protective effect.
This result was confirmed by histological study, In the current study data revealed that significant which revealed apparent normal histological struc- increase in the activities of liver enzymes (AST,
ture of heart in all treated rats with fennel seeds. ALT and ALP) in feeding rats with high fat-diet.
Epidemiologic studies have shown an inverse These elevations in liver enzymes may be attributed
correlation between HDL-C level and the risk of to their release from the cytoplasm into the blood cardiovascular disease. Increasing the HDL cho- circulation after rupture of the plasma membrane, lesterol level by 1mg may reduce the risk of car- cellular damage. This result confirmed by histo-
diovascular disease by 2 to 3 percent [40] . The logical changes of liver sections of positive control present data agreed with Fatiha et al. [41] who rats, which showed congestion of hepatic sinusoid,
reported that hyperlipidemic rats treated with fennel vacuolization of hepatocytes and necrosis of spo-
extract had significant decrease in plasma levels radic hepatocytes as well as fatty changes of hepa-
of TL, TG, TC, LDL-C and VLDL, and significant tocytes. This observed in the elevations were agreed
increase in HDL-C level. This result suggests that with Arkkila et al. [47] who reported that elevated
cholesterol-lowering activity of the fennel can activity of serum AST are a common sign of liver
result from a rapid catabolism of LDL-C through and cardiovascular diseases. The observed increases
its hepatic receptors for final elimination in the in serum AST and ALT levels may be attributed to
form of bile acids as demonstrated by Guimaraes excessive release of such enzymes from the dam-
et al. [42] . Cao and Prior, [43] suggested that the aged liver cells as a result of hyperlipidemia into
hypolipedemic activity of fennel could be attributed the blood circulation. Where, there is an inverse
to the presence of the valuable polyphenolic com- relationship between the liver activity and the level pounds especially tannins, and flavonoids. Eleni of enzymes in serum. Since AST and ALT were
and Bairaktari, [40] demonstrated that flavonoids significantly higher in fatty liver and the severity
and anthocyanins, a heterogeneous group of of fatty liver was positively related to increases in polyphenols, have exhibited a variety of pharma- hyperlipidemia, so AST and ALT were significantly
cological activities, including the antiatherogenesis higher in hyperlipidemic cases [48] . This result was
effect. Anethole (t-anethole) that is the main com- in accordance with Tebib and Rouanet, [49] who pound in all fennel volatile oils possesses significant showed that an activity of liver enzymes increases
antioxidant activity. The presence of t-anethole in hypercholesterolemic animals. The uptake of
and flavonoids content in fennel may be associated LDL-C is dependent on receptors in plasmatic
with lowering TL, TC, TG and LDL-c levels. So membrane. This may be happened in hepatic cells
fennel suggested being a new alternative for clinical of the animal fed cholesterol-supplemented diets, Amr A. Rezq 109
explanatory their higher LDL-C. Eman et al. [50] significantly decreased in hyperlipidemic control
showed highly significant increase in serum levels rats when compared with normal control rats. GSH
of AST and ALT. In addition to, many histopatho- is known as antioxidant, which is usually present
logical and histochemical changes were detected as the most abundant low-molecular mass thiol in
in liver tissue of the hyperlipidemic rats. Jain et most organisms. It has various functions in the
al. [38] demonstrated that hyperlipidemia is asso- defense against oxidative stress and xenobiotic
ciated with hepatic fat accumulation. Amin and toxicity. It can act as an electron donor for glu-
Nagy, [51] also, indicated that serum AST and ALT tathione peroxidase (GPX) in animal cells, and
concentrations was significantly higher in the high also directly reacts with ROS. GSH is readily
fat diet rats compared to the control rats. The oxidized to glutathione disulfide (GSSG) by glu-
elevation effect of high fat diet on liver functions tathione peroxidase, as well as by the reaction with
may be related to oxidative stress, which increased ROS, which may subsequently cause the reduction
in metabolic syndrome due to dyslipidaemia result- in GSH levels. The efficiency by which glutathione
ing from increased levels of free fatty acids and peroxidase can scavenge peroxides increases with
TG that led to increased formation of foam cells, increasing GSH concentration. Increasing intrac-
rendering LDL-C less dense and more vulnerable ellular GSH is associated with increasing the ability
to oxidation and uptake by macrophages [52] . of cells to scavenge strong oxidants. Conversely,
decreases activities of GSH and GPX enzymes
In contrast, the present results revealed that results in greater damage as a result of oxidative
feeding rats with high fat-diet supplemented with stress [59] .
different levels of fennel seeds produce significant
decrease in serum AST, ALT and ALP levels and It is well known that free radical scavenging
improved liver functions compared to the feeding enzymes like SOD protects the biological systems
from oxidative stress. The current study showed a rats with high fat diet only. This effect may be
related to antioxidant properties of fennel. Ozbek significant decrease in the activities of SOD in
hyperlipidemic rats as compared to normal rats. et al. [14] reported that essential oil of fennel had hepatoprotective activity against carbon tetrachlo- This depletion could be due to an enhanced pro- duction of free radicals as a result of lipid peroxi- ride (CCl4) which induces liver injury in rat’s dation. The increased in MDA was consistent with model as it decreases levels of serum AST, ALT, the observation that these free radicals reduced the ALP and bilirubin. Fennel contains several types of phenolic and flavonoids that is known as anti- activity of the endogenous antioxidant enzyme SOD [60] . oxidants and had strong free radical scavenging.
It is of the most effective antioxidants in the food industry [15] . D-limonene and ß-myrcene com- The present results agreed with Prasad et al. [61] who showed significant increase in serum pounds found in fennel (Foeniculum vulgare) have a potent hepatoprotective action [53] . Lately, chem- MDA levels, a decrease in SOD activity in hyper- ical composition of fennel demonstrated the pres- cholesterolemic. These results suggest that hyper- cholesterolemia produces oxidative stress in the ence of anethole as the most potent antioxidant myocardium which may be due to a decrease in [54] . Presumably, fennel functions as an antioxidant, the antioxidant reserve. Amin and Nagy, [51] re- stops the propagation of the peroxidative chain ported that high fat-diet generates oxidative stress reaction, by inhibiting 5-hipoxigenase [55] . in rats as shown by a marked increase in the levels
Oxidative stress is known to describe the lack of MDA and a distinct diminution in GSH enzyme,
of equilibrium between the production of free as well as activities of the antioxidant enzyme
radicals and the antioxidant protective activities catalase. All showed reduced activity in hyperlip-
in a given organism [56] . Hyperlipidemia enhanced idemic rats. Recently, Yogendrasinh and Rajendra,
oxidative stress with the oxidation of low density [62] found that there was significant lipid-
LDL-C [57] . Free radicals have been implicated in peroxidation in hyperlipidemic rats as indicated
the pathogenesis of many degenerative disease, by increased MDA levels compared with normal
including diabetes, and atherosclerosis and cancer rats.
[58] . The levels of reactive oxygen species are con-
The present study showed that lipid–peroxida- trolled by antioxidant enzymes namely, SOD, GSH,
tion was increased significantly in hyperlipidemic CAT, and non-enzymatic scavengers [63] . These
control rats as indicated by the increased in serum antioxidants are produced either endogenously or
MDA level compared with the normal control rats. received from exogenous sources and protect cells
The activities of CAT and GPX enzymes were against oxidative stress [64] . The protective antiox- 110 Beneficial Health Effects of Fennel Seeds (Shamar) on Male Rats
idant mechanisms employ both enzymatic and non- Conclusion:
enzymatic substances such as phenolic and flavones In generally, hyperlipidaemia is associated with [65] . Feeding rats with high fat-diet supplemented abnormalities in fatty acid metabolism. It is char- with 5%, 10% and 15% fennel seeds produced acterized by an increase cardiovascular risk. Treat- significant reduce in serum MDA and significant ing with fennel turned back total lipids to the increase the activities of CAT, GPX and SOD normal values. Fennel exhibited good radical scav- enzymes compared to the feeding rats with high enging activity and enhance the activities of anti- fat-diet only. Therefore, fennel seeds reduced oxidant enzymes. Essential oil of fennel has also oxidative stress and improve antioxidant defense. strong radical scavenging and has a strong protec- This action of fennel may be related to its antiox- tive effect against lipid peroxidation. Antioxidative idant activity. This result agreed with Roberto et properties and radical scavenging activity may be al. [66] who showed that fennel extract has antiox- the possible mechanisms by which fennel amelio- idant effects, reducing MDA level and increasing rated the total lipids, cholesterol, triglycerides and plasma SOD as well as CAT activities. Aqueous LDL-C. Anethole (t-anethole) is the main com- extracts of fennel provide to have antioxidant pound in all fennel volatile oils possesses significant activity higher than some well known antioxidant antioxidant activity. The presence of t-anethole such as ascorbic acid [67] . Biochemical assays and flavonoids content in fennel may be associated revealed a significant increase in the content/ with lowering total lipids, cholesterol, triglycerides activities of phase I and phase II enzymes with a and LDL-C levels. So fennel suggested being a significant enhancement in the activities of antiox- new alternative for clinical management of hyper- idant enzymes. These findings were indicative of lipidemic patients. the chemopreventive potential of fennel against
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