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IOSR Journal Of Pharmacy www.iosrphr.org (e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219 Volume 8, Issue 5 Version. I (May 2018), PP. 81-96
81
The chemical constituents and pharmacological effects
of
Foeniculum vulgare
- A review
Prof Dr Ali Esmail Al-Snafi
Department of Pharmacology, College of Medicine, University of Thi qar, Iraq.
Corresponding Author: Prof Dr Ali Esmail Al-Snafi
Abstract: As a result of accumulated experience from the past generations, today, all the
world’s cultures have an extensive knowledge of herbal medicine. Plants are a valuable source of a
wide range of secondary metabolites, which are used as pharmaceuticals, agrochemicals, flavours, fragrances,
colours, biopesticides and food additives. This study was designed to highlight the chemical constituents and
pharmacological effects of
Foeniculum vulgare
.
Keywords:
Foeniculum vulgare
, chemical constituents, pharmacology, herb, medicinal plant
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Date of Submission: 28-05-2018
Date of acceptance: 11-06-2018
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I. INTRODUCTION:
As a result of accumulated experience from the past generations, today, all the
world’s cultures have an extensive knowledge of herbal medicine. Plants are a valuable source of a
wide range of secondary metabolites, which are used as pharmaceuticals, agrochemicals, flavours, fragrances,
colours, biopesticides and food additives(1-30).
Foeniculum vulgare
contained saponins, flavonoids, cardiac glycosides, sterols,
triterpenes, coumarins, proteins, volatile oils, trace elements and vitamins. It possessed CNS,
reproductive, urinary, antidiabetic, antioxidant, anticancer, antimicrobial, cardiovascular, immunological,
dermatological and many other pharmacological effects. This study was designed to highlight the chemical
constituents and pharmacological effects of
Foeniculum vulgare
.
Plant profile:
Synonyms:
Anethum dulce
DC.,
Anethum foeniculum
L. ,
Anethum minus
Gouan,
Anethum
panmori
Roxb.,
Anethum panmorium
Roxb. ex Fleming,
Anethum pannorium
Roxb.,
Anethum rupestre
Salisb.,
Foeniculum azoricum
Mill.,
Foeniculum divaricatum
Griseb.,
Foeniculum dulce
Mill.,
Foeniculum giganteum
Lojac.,
Foeniculum officinale
All.,
Foeniculum panmorium
(Roxb.) DC.,
Foeniculum piperitum
C. Presl,
Foeniculum rigidum
The chemical constituents and pharmacological effects of Foeniculum vulgare - A
review
82
Brot. ex Steud,
Foeniculum vulgare
var. capillaceum Burnat,
Foeniculum vulgare
subsp.
capillaceum (Burnat) Holmboe,
Foeniculum vulgare
var. dulce (Mill.) Batt. & Trab.,
Foeniculum vulgare
var. inodorum Maire,
Foeniculum vulgare
subsp. piperitum (C.
Presl) Bég. ,
Foeniculum vulgare
var. piperitum (C. Presl) Ball,
Foeniculum vulgare
var.
sativum C. Presl,
Foeniculum vulgare
subsp. sativum (C Presl) Janch ex Holub,
Ligusticum
foeniculum
(L) Roth, Ligusticum foeniculum (L) Crantz,
Meum foeniculum
(L) Spreng,
Selinum foeniculum
E. H. L. Krause,
Seseli foeniculum
Koso-Pol and
Tenoria romana
Schkuhr ex Spreng(31).
Taxonomic classification:
Kingdom: Plantae, Phylum: Spermatophyta, Subphylum: Angiospermae, Class:
Magnoliopsida, Order: Apiales, Family: Apiaceae, Genus: Foeniculum, Species:
Foeniculum
vulgare
(32-33).
Common Names:
Arabic: shmar, shumar, bisbas, razianj, haba helwa; Brazil: Endro, erva-doce, funcho;
Chinese: hui xiang; Cuba: hinojo común English fenne, common fennel, Florence fennel,
Roman fennel, sweet fennel, anise, sweet anise, aniseed, aniseed weed; French: aneth
doux, fenouil, fenouil commun, fenuil doux; Germany: Echter Fenchel, Garten- Fenchel,
Gemüsefenchel, Gewürzfenchel, wilder Fenchel; Hindi: Badi saunf, Bari saunf, Moti saunf,
Saunf, Saumph; Indonesia: adas, adas londo, hades; Iran: Razianeh, Italy: finocchio;
Japan: ui-kyo; Laos: phak s'i; Malaysia: adas pedas; Netherlands: venkel
Philippines: anis, haras; Portuguese: funcho; South Africa: vinkel; Spanish: fonol, hinojo;
Sweden: faenkaal, fänkål; Thailand: phakchi-duanha, thian-klaep, yira(33).
Distribution:
It probably originated from southern Europe and the Mediterranean region. It is
cultivated throughout much of the world as a spice, medicinal or essential oil plant, or as a
vegetable, and has become naturalized in many places. Now it is recorded in Africa:
(Algeria, Egypt, Libya, Morocco, Tunisia, South Africa); Asia: (Georgia, Afghanistan, Iran,
Iraq, Palestine, Jordan, Lebanon, Syria, Turkey, Pakistan); Europe: (Ukraine, Albania,
Bosnia, Herzegovina, Bulgaria, Croatia, Greece, Italy, Montenegro, France,
Portugal, Spain, United Kingdom); Australasia: (Australia, New Zealand); Northern
America: (Mexico; United States); Southern America: (Brazil, Costa Rica, El
Salvador, Guatemala, Honduras, Venezuela, Argentina, Chile, Paraguay, Uruguay)(34-35).
Description:
Foeniculum vulgare
is a biennial plant with a thick rootstock, erect, much-branched,
smooth, often 1 meter or more in height. Leaves are 2-, 3-, or 4-pinnate and about 20
centimeters long; the segments are filiform and 2 to 4 centimeters long. Umbels are 5 to 10
The chemical constituents and pharmacological effects of Foeniculum vulgare - A
review
83
centimeters in diameter; the rays number: 8 to 15, about 2 to 3 centimeters long, but longer
in fruit, each with 20 to 30 pedicelled yellow flowers. Fruit is ridged, very aromatic, oblong
or ellipsoid, about 5 millimeters long. Seeds are somewhat dorsally compressed(36-37).
Traditional uses:
Fennel was considered as one of the oldest medicinal plants and culinary herbs. It
was used over 4000 years ago. Fennel was used by the ancient Egyptians as a food and
medicine, and it was considered a snake bite remedy in ancient China. It was used since
ancient times to treat menstrual disorders, dyspepsia, flatulence and cough, and to reduce
the griping effect of laxatives(38).
Foeniculum vulgare
was widely used in traditional Arabian
medicine as diuretic, appetizer, and digestive(39). The fruit, seeds and young leaves were
used for flavoring sweets, dishes and dainties. The young leaves, raw or cooked, were used
as flavoring. The seeds have an anise-like flavor and used as flavoring. The infused fruits
were used as carminative. Roots were employed as purgative. Crushed fruits were
inhaled to counter faintness. Infusion of fruit was used for flatulence. Shoots of young
plant were used as carminative and in respiratory disorders. Juice of fruit was used to
improve eyesight. Decoction was gargled as a breath freshener or applied as an eyewash.
Decoction of seeds was used to regulate menses and as diuretic and emmenagogue.
Poultice was used to relieve breast swelling in nursing mothers. Infusion of seeds was used
for stomatitis, abdominal cramps, colic, flatulence. Fennel water (aqua foeniculi) was used
for colic and flatulence in children. Hot infusion of fruit and of roots was used for
amenorrhea. Infusion of roots was given for toothaches and postpartum pains. Infusion of
seeds was used for flatulence in babies. Infusion of root was also used for urinary
disorders. Oil was used for flatulence and intestinal worms. Paste of seeds or fruit were
used in cooling drinks for fevers. Seeds also used as stimulant and to enhance libido, to
increase breast milk production, for the treatment of venereal diseases, easing childbirth and
soothing cough(36).
Parts used: Whole plant, roots, seeds and oil of seed(36).
Physicochemical parameters of the essential oil of fennel fruit:
Moisture %: 3.35- 4.75; Solubility: alcohol, cloroform, carbon tetrachloride, hexane; acid
value (mg/KOH/g): 1.5-2.45; Saponofication value (mg/KOH/g): 121.50-145.75; Ester value:
116.00-141.30; Peroxide value (mEq/kg): 5.65-6.45; Iodine value (g/g): 94.25-98.5;
Refractive index at 25oC: 1.5465±0.30-1.5575±0.25; Congealing point (16.4oC):
16.4±0.5- 16.7±0.5; Optical rotation (-2.25 ± 0.70 to + 10.25 ± 0.43) - ( -2.10 ± 0.36 to +
10.35 ± 0.45) and Specific gravity at 25oC: 0.978±0.035 -0.985±0.032 (40).
Chemical constituents:
The preliminary phytochemical study revealed the presence of saponins, flavonoids,
cardiac glycosides, sterols, triterpenes, coumarins and volatile oils (39, 41). It
also contained
The chemical constituents and pharmacological effects of Foeniculum vulgare - A
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84
protein, fat, minerals, fibre and carbohydrates. The minerals and vitamins identified in
Foeniculum vulgare
were included calcium, potassium, sodium, iron, phosphorus, thiamine,
riboflavin and niacin (42).
Triterpenes, flavanoid glycosides, smaller terpenes (monoterpenoids, sesquiterpenoids
and diterpenoids) and reducing sugars were isolated from the seeds of
Foeniculum
vulgare
(43)
.
Total phenolic content in organic fennel oil was 262.59 ± 15.5 mg Gallic Acid
Equivalents/l(44). The phenolics identified in the fruit of this plant were neochlorogenic acid
(1.40%), chlorogenic acid (2.98%), gallic acid (0.169%), chlorogenic acid (6.873%), caffeic
acid (2.960%),
p
-coumaric acid (4.325%), ferulic acid-7-
o
-glucoside (5.223%), quercetin-7-
o
-
glucoside (3.219%), ferulic acid (3.555%), 1,5 dicaffeoylquinic acid (4.095%), hesperidin
(0.203%), cinnamic acid (0.131%), rosmarinic acid (14.998%), quercetin (17.097%), and
apigenin (12.558%)(45). However, Parejo
et al
., isolated 3- caffeoylquinic acid, 4-
caffeoylquinic acid, 1.5-Odicaffeoylquinicacid, rosmarinic acid, eriodictyol-7-Orutinoside,
quercetin-3-O-galactoside, kaempferol-3-Orutinoside, kaempferol-3-O-glucoside,
hydroxylcinnamic acid derivatives, flavonoid glycosides and flavonoid aglycones from the
aqueous extract of fennel fruits (46). The furocoumarins imperatorin, psoralen, bergapten,
xanthotoxin and isopimpinellin were isolated from the methylene chloride extract. The
flavonoids isorhamnetin 3-
O
-α-rhamnoside, quercetin and kaempferol were isolated from the
ethyl acetate extract, whereas quercetin 3-
O
-rutinoside, kaempferol 3-
O
-rutinoside and
quercetin 3-
O
- β-glucoside were isolated from the methanol extract (47).
Nutritional analysis showed that the plant contained moisture:90.21 g, Energy:
31 kcal, Protein: 1.24 g (Essential amino acids: Leucine: 0.63 g, Isoleucine: 0.73 g,
Phenylalanine: 0.45 g, Tryptophane: 0.53 g and Non-essential amino acid (Glycine:
0.55 g, Proline: 0.53 g), Total lipid (fat): 0.2 g (Fatty acids, total saturated: 0.09 g, Fatty
acids, total monounsaturated: 0.068 g, Fatty acids, total polyunsaturated: 0.169 g),
Carbohydrate: 7.3 g, Total dietary fiber: 3.1 g, Sugars: 3.93 g, Minerals (Calcium:
49 mg, Iron: 0.73 mg, Magnesium: 17 mg, Phosphorus: 50 mg, Potassium: 414 mg,
Sodium: 52 mg, Zinc: 0.2 mg), Vitamins (Vitamin: 12 mg, Thiamin: 0.01 mg, Riboflavin:
0.032 mg, Niacin: 0.64 mg, Vitamin: 0.047 mg, Folate: 27 μg, Vitamin A: 48 μg
Vitamin E: 0.58 mg, Vitamin K: 62.8 μg)(47).
Essential oils were isolated from fennel aerial parts collected in Cape Verde and
from a commercial fennel EO of Portugal were analyzed by NMR, GC and GC-MS. trans-
Anethole (32 and 30%, respectively), limonene (28 and 18%, respectively) and fenchone
(10% in both cases) were the main compounds identified in the essential oils isolated
from fennel from Cape Verde and Portugal, respectively(48).
Foeniculum vulgare
essential oil from Turkey contained 74.8% (E)-anethole, 11.1%
limonene, 4.7% methyl chavicol, 2.5% fenchone and 1.3% α-pinene(49).
The chemical constituents and pharmacological effects of Foeniculum vulgare - A
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85
Sing
et al
., investigated the chemical components of volatile oil of
Foeniculum
vulgare
( from Gorakhpur), they found that the oil contained (%): acetic acid-ethyl ester:
trace, 3-Methylbutanal: 0.1, 2-Methylbutanal: trace, Alpha-Thujene: trace, Alpha-Pinene: 0.2,
Camphene: trace, Sabinene: trace, Beta-Pinene: 0.2, Myrcene: 0.1, Delta-3-Carene: 0.1,
Alpha-Terpinene: trace, p-Cymene: 3.1, Limonene: 3.1, 1,8-Cineole: 0.1, trans-beta-
Ocimene: 0.1, Gamma-Terpinene: 2.1, Fenchone: 8.6, Linalool: 1.2, Camphor: 0.3, Beta-
Terpineol: trace, Terpinen-4-ol: 0.2, Alpha-Terpineol: 0.2, Methyl chavicol: 4.7, Fenchyl
acetate: 0.2, Cuminal: 0.4, cis-Anethole: 0.4, p-Anisaldehyde: 0.5, trans-Anethole: 70.1,
Thymol: 0.1, Alpha-Copaene: 0.1, Beta-Caryophyllene: 0.2, Alpha-Humulene: tracea and
Delta-Cadinene: trace (50).
However, Upadhyay , isolated 36 components from the essential oil of
Foeniculum
vulgare
from Gorakhpur, Uttar Pradesh, India. The main constituents of essential oil were
identified as 9-octadecenoic acid (18.56%), 8Z)-14-methyl-8-hexadecenal (7.75%), pentad
ecanecarboxylic acid (4.25%), o-benzenedicarboxylic acid (14.47%), 1,3,3-trimethyl-2-vinyl-1-
cyclohexene (10.77%), 2-methyl-3-oxoestran- 17-yl acetate (5.46%), 1H-benzocycloheptene
(10.71). However, the major and minor constituents isolated from Fennel (
Foeniculum
vulgare
) essential oil were included (0.71%) Tetradecane, Hexadecane; (2.05%) Ethanone,
1-(4-methyl-3-cyclohexen-1-YL)-1-(4-methyl-3-cyclohexen-1-YL)ethanone, 2-propanone; (3.67%)
H-Benzocycloheptene, 2,4a,5,6,7,8,9, 9a-octahydro-3,5,5-trimethyl-9-methylene-, Longifolene;
(0.15%) Phenylmethyl ester; (2.25%) cis-(-)-2,4a,5,6,9a-Hexahydro-3,5,5,9-tetramethyl (1H))
benzocycloheptene; (10.71%) 1H-Benzocycloheptene; (0.26%) m-Methyl acetophenone;
(0.21%) alpha.-Caryophyllene; (0.14%) 2-Cyclopenten-1-one, 2-hydroxy-3-methyl-Corylon;
(0.54%) p-Guaiacol; (0.48%) 2-(4a,8-Dimethyl-2,3,4,4a,5,6-hexahydro-naphthalen-2-yl)-prop-
2-en-1-ol; (0.66%) Vetivenene Neoisolongifolene, Aromadendrene; (0.90%) Anthracene,
1,2,3,4,5,6,7,8-octahydro-1-methyl-; (1.74%) 1-Methyl-6-(3-methylbuta-1,3-dienyl)-7-oxabicyclo
[4.1.0] heptane; (1.12%) 1-hydroxy-2-methoxy-2-methoxy-4-methylbenzene; (0.26%) 1-
(2,3-Dihydroindol-1-yl)-4-phenyl-butan-1,4-dione; (0.26%) 5,5 Dimethyl-3-vinyl cyclohex-2-en-
1-one; (0.54%) 2-Methoxy-4-ethylphenol, 1,2-Dimethoxy-4-methylbenzene; (0.37%) Bis(4-
methylphenyl) methanedisulfonate; (0.32%) (-)-5-xatricyclo [8.2.0.0(4,6)] Dodecane, Cedran-
9-one; (1.22%) 2,2-dimethyl-3-phenylpropanoate; (0.29%) -Methyl-6-(3-methylbuta-1,3-
dienyl)-7-oxabicyclo [4.1.0] heptane; (0.45%) 2,7-dimethyloct-7-en-5-yn-4-yl ester; (2.04%)
2-Methyl-6-(4-methyl-1,3-cyclohexadien-1-yl)-2-hepten-4-one; (3.16%) 3-Methyl-2-butenoic
acid; 5.46 2-Methyl-3-oxoestran-17-yl acetate; (0.70%) 3,3,6-Trimethyl-1-indanone; (10.77%)
1,3,3-Trimethyl-2-vinyl-1-cyclohexene; (14.47%) o-Benzenedicarboxylic acid; (0.49%) 1-
Isopropyl-1,2,3,4-tetrahydroisoquinoline; (0.20%) 3,4-Dimethyl-1,5-cyclooctadiene; (1.84%)
2-hydroxy-1-(hydroxymethyl)ethyl ester; (4.25%) Pentadecanecarboxylic acid; (7.75%) 8Z)-
14-Methyl-8-hexadecenal; (18.56%) 9-octadecenoic acid and (1.00%) 2-cis,cis-9,12-
Octadecadienyloxyethanol (51).
The chemical constituents and pharmacological effects of Foeniculum vulgare - A
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86
Analyses (GC and GC/MS) of
Foeniculum vulgare
roots and schizocarp ( from the
city of Niš, Serbia) essential oils and diethyl ether extracts resulted in identification of 89
different components. The most abundant classes of constituents were the phenylpropanoids
(69.5-85.5%) and monoterpenoids (11.7-26.9%). The dominant volatile metabolites of
schizocarps were fenchone (13.3-18.8%) and (
E
)-anethole (66.1-69.0%). Contrary to that,
terpinolene (6.2-6.5%) and dillapiole (71.4-77.5%) were the major volatiles of fennel roots (52).
The chemical analysis of the aerial parts and fruits of
Foeniculum vulgare
Mill.
subsp.
piperitum
collected from North Western Mediterranean coastal strip near El-Salloum,
Egypt showed the presence of the following fatty acids(%): capric acid 2.83 and3.23,
undecanoic acid 18.21 and 20.09, lauric acid 2.13 and 2.45,myristic acid 10.51 and
11.20, pentadecanoic acid 1.79 and 2.10, pentadecenoic acid 7.33 and 7.68,
pentadecadienoic acid 9.29 and 10.91, palmitic acid 31.51 and 33.47, stearic acid 0.69
and 0.77, oleic acid 1.55 and 0.40, linolieic acid 0.43 and 0, linolenic acid 0.65 and
0.38, arachidic acid 0.76 and 1.31, behenic acid 0 and 0.41, erucic acid 0.87 and 1.33
and tetracosenoic acid 1.89 and 0 respectively. Hydrocarbons and sterols identified in the
aerial parts and fruits of
Foeniculum vulgare
(100) were included:
n
-Decane 3.75 and 4.29,
n
-Dodecane 2.16 and 2.84,
n
-Tridecane 0.88 and 0.34,
n
-Pentadecane 0.47 and 1.09,
n
-
Hexadecane 0.49 and 0.65,
n
-Heptadecane 1.64 and 1.44,
n
-Octadecane 1.71 and 2.19,
n
-
Nonadecane 0 and 1.11,
n
-Eicosane 5.89 and 10.43
n
-Monocosane 2.72 and 1.88,
n
-
Docosane 0.96 and 1.39,
n
-Tricosane 0 and 2.37,
n
-Tetracosane 0.45 and 0.89,
n
-
Pentacosane 2.25 and 4.59,
n
-Hexacosane 2.86 and 5.51,
n
-Heptacosane 0.41 and 0.27,
n
-
Octacosane 0.37 and 0.44,
n
-Nonacosane 0.79 and 1.76,
n
-Triacontane 0.53 and 1.35,
n
-
Monotriacontane 0.48 and 0.89,
n
-Dotriacontane 2.09 and 2.28,
n
-Tetratriacontane 4.52 and
3.34,
n
-Hexatriacontane 10.27 and 0,
n
-Octatriacontane 7.91 and 2.83,
n
-Tetracontane 1.71
and 0.84, Cholesterol 5.52 and 5.95, β–Sitosterol 5.52 and 5.95, Campesterol 3.33 and
4.04 and Stigmasterol 14.86 and19.04 respectively(47).
Cultivated and wild growing samples of
Foeniculum vulgare
from R. Macedonia were
studied for their volatiles and fatty acid composition. The main essential oil components
were: trans-anethole >80%, estragole < 6%, limonene < 6%, anisaldehyde < 1% and 0.5
% fenchone. The dominant fatty acid was (petroselinic and oleic acid) 75.0-82.8%, followed
by linoleic acid 10.8-16.2%, palmitic 4.3-6.9%, stearic 1.2-1.7% and myristic acid 0-2.9%
(53).
Pharmacological effects:
Effects on urinary system:
The ethanolic fruit extract (500 mg/kg dose) showed, statistically, highly significant
diuretic effect in rats, that was evident both after 5 (P<0.0l) and 24h (P
<
0.05) of its
administration. The plant-induced diuresis comparable to that of urea (960 mg/kg) and was
The chemical constituents and pharmacological effects of Foeniculum vulgare - A
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87
almost double that of the control animal's urine output. The diuresis was not associated with
changes in sodium and/or potassium excretion (39).
The diuretic activity of aqueous and 80% methanol extracts of
Foeniculum vulgare
Mill. (Apiaceae) leaf was evaluated in rats using different doses of aqueous or 80%
methanol extract (100, 200 and 400 mg/kg) orally. Rats treated with 200 and 400 mg/kg
doses of aqueous and 80% methanol extract of
Foeniculum vulgare
showed an increased
urine volume (P<0.001). However, 100 mg/kg dose of both extracts failed to produce
significant increase in 24 h urine volume compared to control groups. Both extracts
increased natriuresis, kaliuresis and chloriuresis (P<0.001) at the middle and higher doses
(54).
CNS effects:
The anxiolytic activity of the essential oil of
Foeniculum vulgare
(50, 100, and 200
and 400 mg/kg) was studied in mice using elevated plus maze (EPM), staircase test (SCT)
and open field test (OFT). In EPM test, 100 and 200 mg/kg doses of the essential oil
significantly increased percent number of entries and time spent in open arms compared to
control. In SCT test, these doses also reduced rearing significantly compared to controls,
while only the 200 mg/kg dose significantly increased number of squares crossed at the
center in the OFT test (55).
The anxiolytic activity of ethanolic extracts of
Foeniculum vulgare
fruit was
evaluated by elevated plus maze, rota rod, open field test, and hole board model in mices.
The efficacy of extract (100-200 mg/kg) was compared with standard anxiolytic drugs
diazepam (1mg/kg). Extract administered animals showed exploratory behavior with all tests
similar to diazepam. The results showed that the extract significantly increased the number
of entries and time spent in the open arm in the elevated plus maze apparatus. In open
field test, the extract showed significant increase in number of rearings, assisted rearing and
number of square crossed (56).
The anxiolytic activity of the crude ethanolic extract of
Foeniculum vulgare
was
studied in albino mice by elevated plus-maze model. The extract at doses of 200 mg/kg
and 400 mg/kg has been found to possess significant anti-anxiety activity on the tested
experimental models. The extract (400 mg/kg) exhibited maximum anti-anxiety effect. At a
higher dose the extract showed increase number of entries and time spent in open arm of
elevated plus-maze model. The effect produced by the extract was comparable to that
of diazepam (57).
The anti-stress and memory-enhancing properties of
Foeniculum vulgare
boiling
water extract (50, 100 and 200 mg/kg, orally) were studied in experimental rats. Urinary
levels of vanillylmandelic acid (VMA) and ascorbic acid in rats were used to evaluate anti-
stress activity. Conditioned avoidance response was measured in normal and scopolamine-
induced amnesic rats to study the memory-enhancing effects. Lipid peroxidation inhibition
The chemical constituents and pharmacological effects of Foeniculum vulgare - A
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88
assay in liver and brain homogenates of rats was used to evaluate antioxidant activity. Daily
administration of
Foeniculum vulgare
extract (50, 100 and 200 mg/kg body weight) 1 h prior
to induction of stress significantly (p < 0.05) altered the stress-induced urinary biochemical
levels of VMA from 395.79 ± 11.23 to 347.12 ± 12.28, 311.21 ± 12.48 and 258.86 ± 10.26
μg/kg, respectively, in 24 h, as well as ascorbic acid excretion levels from 65.74 ± 9.42 to
78.59 ± 8.44, 108.41 ± 15.62 and 125.82 ± 16.94 μg/kg within the same period,
respectively. These changes occurred in a dose-dependent fashion, and the levels in the
control groups were unchanged. The memory deficits induced by scopolamine (1mg/kg, ip)
in rats was reversed by
Foeniculum vulgare
dose-dependently. The extract also exhibited
potent antioxidant effect by inhibition of lipid peroxidation in both rat liver and brain
homogenates to a greater extent than the standard antioxidant, ascorbic acid (58).
The antidepressant effect of
Vetiveria zizanioides
and
Foeniculum vulgare
in
comparison with antidepressant drug fluoxetine was investigated in depressive behavior in
albino rats. Both Forced swimming test and Tail suspension test were used for screening
antidepressant effect. The ethanolic extract of
Vetiveria zizanioides
(100mg/kg) and
Foeniculum vulgare
(200mg/kg) together, fluoxetine (10mg/kg) and saline were administered
30 minutes prior to the tests and the immobility period was recorded for 6 minutes.
Vetiveria zizanioides
(100mg/kg) and
Foeniculum vulgare
(200mg/kg) produced significant
antidepressant effect by reduction in immobility period as compared to control. But when
given both together they were equally effective as fluoxetine (10mg/kg) (59).
The antidepressant effects of methanolic extract of
Foeniculum vulgare
fruits
(MEFV) was investigated using force swim test in rats (FST), potentiation of norepinephrine
(NE) toxicity in mice and haloperidol induce catalepsy (HIC) in mice. The extract of
Foeniculum vulgare
(250 and 500 mg/kg) was administered orally to rats used in FST and
500mg/kg was administered in HIC and in NE toxicity test in mice. The dose of 250mg/kg
and 500mg/kg of extract significantly (P<0.001) reduced the immobility times in rats, 500
mg/kg showed more potent effect than imipramine (30mg/kg). In NE toxicity model it was
observed that MEFV dose not interfere with adrenergic system. A significant (P<0.001)
reduction in the duration of catalepsy was observed in the MEFV treated group and
Fluoxetine group as compared to the haloperidol treated group. In HIC, mice were sacrificed
on the seventh day and TBARS, glutathione, nitrite activities were estimated. Monoamine
oxidase inhibiting effect and anti-oxidant effect of
Foeniculum vulgare
may be contributing
favorably to the antidepressant-like activity (60).
The nootropic and anticholinesterase potential of
Foeniculum vulgare
was studied in
mice. Methanolic extract of the whole plant of
Foeniculum vulgare
administered for eight
successive days ameliorated the amnesic effect of scopolamine (0.4 mg/kg) and aging-
induced memory deficits in mice. The passive avoidance paradigm was used as
exteroceptive behavioral model for assessing memory.
Foeniculum vulgare
extract increased
step-down latency and acetylcholinesterase inhibition in mice significantly. The authors
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postulated that
Foeniculum vulgare
can be employed in treatment of cognitive disorders
such as dementia and Alzheimer's disease (61).
Gastrointestinal effects:
Both
Foeniculum vulgare
essential oil and anethole (100 mg/kg, orally) provided
significant protection toward ethanol induced gastric lesions in rats (62).
The gastric ulcer protective potential of an aqueous suspension of
Foeniculum
vulgare
was evaluated against different acute gastric ulcer models, pyloric ligation (Shay),
hypothermic restraint stress, indomethacin and by necrotizing agents (80% ethanol, 0.2 M
NaOH and 25% NaCl). Pretreatment with
Foeniculum vulgare
suspension, 250 and 500 mg/
kg bw orally (intraperitoneally in Shay rat model) showed a dose-dependent ulcer protective
effects in all the models. Furthermore, it offered protection against ethanol-induced
depletion of gastric wall mucus, replenished the reduced nonprotein sulfhydryls concentration
and modulated malondialdehyde contents in the gastric tissue. Ethanol induced
histopathological lesions was reversed by
Foeniculum vulgare
(63).
The anti-ulcerogenic and antioxidant effects of aqueous extracts of
Foeniculum
vulgare
(FVE) (75, 150 and 300 mg/kg) was evaluated in ethanol-induced gastric lesions in
rats. Pretreatment with FVE significantly reduced ethanol-induced gastric damage. The anti-
ulcerogenic effect of FVE was highest in 300 mg/kg group (P < 0.001). Pretreatment with
FVE also significantly reduced the MDA levels, and significantly increased GSH, nitrite,
nitrate, ascorbic acid, retinol and β-carotene levels (64).
The antiulcerogenic property of
Foeniculum vulgare
was evaluated in Wistar albino
rats. The aqueous suspension of fennel was given in two doses (250 and 500 mg/kg b w,
orally). Gastric acid secretion studies were undertaken using pylorus ligated (Shay) rats.
Gastric lesions in the rats were induced by noxious chemicals including ethanol, strong
alkalis and indomethacin. The levels of gastric wall mucus (GWM), nonprotein sulfhydryls
(NP-SH) and malondialdehyde (MDA) were also measured in the glandular stomach of rats
following ethanol administration. The gastric tissue was also examined histologically. In
pylorus-ligated Shay rats, the suspension of fennel significantly reduced the basal gastric
acid secretion, titratable acid and stomach ulceration (64 %, 39 % and 100 %), respectively.
The suspension significantly (P < 0.001, P < 0.01 and P < 0.01) attenuated gastric
ulceration induced by necrotizing agents (80 % ethanol, 0.2 mol/l NaOH, 25 % NaCl)
respectively and indomethacin was found to be (P < 0.01). The cytoprotective and antiulcer
effect was further confirmed histologically. Furthermore, the suspension significantly
replenished the ethanol-induced depleted levels of GWM (P < 0.001), NP-SH (P < 0.05)
and diminished (P < 0.01) (MDA) concentration of the stomach (65).
The anti-colic effectiveness of fennel seed oil emulsion was studied in infantile
colic ( 125 infants, 2 to 12 weeks of age). The use of fennel oil emulsion eliminated colic,
according to the Wessel criteria, in 65% (40/62) of infants in the treated group, which was
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significantly better than 23.7% (14/59) of infants in the control group (P < 0.01). Side effects
were not reported for infants in groups during the trial (66).
Hydro distilled fruit extract of
Foeniculum vulgare
showed prominent antispasmodic
activity in acetylcholine induced spasm. Also hydro distilled extract of
Foeniculum vulgare
showed receptor blocking action (antispasmodic) as that of standard agent (atropine) on
isolated guinea pig ileum (40).
The laxative effect of a phytotherapic compound containing (
Pimpinella anisum
L.,
Foeniculum vulgare
Miller,
Sambucus nigra
L., and Cassia
augustifolia
)
was evaluated by a
randomized, crossover, placebo-controlled, single-blinded trial included 20 patients with
chronic constipation. Half of the subjects were received the phytotherapic compound for 5-
day period, whereas the other half received placebo for the same period. Both treatment
periods were separated by a 9-day washout period followed by the reverse treatment for
another 5-day period. Mean colonic transit time assessed by X ray was 15.7 hours (95%CI
11.1-20.2) in the active treatment period and 42.3 hours (95%CI 33.5-51.1) during the
placebo treatment (P < 0.001). Number of evacuations per day increased during the use of
active tea from the second day of treatment (P < 0.001). Patient perception of bowel
function was improved (P < 0.01), but quality of life did not show significant differences
among the study periods. The findings of the randomized controlled trial revealed that the
phytotherapic compound exerted laxative effects and was a safe alternative option for the
treatment of constipation (67).
Foeniculum vulgare
ethanolic
fruit extract administration (500 mg/kg) to rats caused
a 33% increase of the collected bile volume that was statistically significant (P<0.0l)
compared with control values. The bilirubin content in the collected bile was similar in both
treated and control groups (39).
Antimicrobial effect:
The antibacterial effects of methanolic extracts of 23 fennel samples were evaluated
against many bacterial isolates. The seed extracts of two samples showed moderate to
good inhibitory activities (MICs=62.5-125μg/ml) against three bacteria (68).
Crude extracts of
Foeniculum vulgare
seeds was investigated for
antimicrobial
activity against
Staphylococcus aureus
,
Micrococcus
spp
and
Entecococcus
spp
.
The
results showed that the ethanolic extract had greater activity against
Micrococcus
spp.
(MIC=250μg/ml) (43).
Antibacterial activity of aqueous and organic
Foeniculum vulgare
seed extracts was
assessed against
Enterococcus faecalis
,
Staphylococcus aureus
,
Escherichia coli
,
Klebsiella
pneumoniae
,
Pseudomonas aeruginosa, Salmonella typhi
,
Salmonella typhimurium
,
Shigella
flexneri
, using agar diffusion assay. Out of the aqueous extracts prepared in three different
ways, hot water extract of seeds (prepared at 40°C) gave better inhibition zones as
compared to extracts prepared at ambient temperature of water and boiling water. Organic
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extracts showed similar results as observed in case of aqueous extracts with some
variations. The extracts prepared in hexane and acetone gave relatively better inhibitory
zones ranging from 9–30 mm (69).
The antimicrobial effect of the methanol, ethanol, diethyl ether, and hexane extracts
of seed of
Foeniculum vulgare
was investigated against
Escherichia coli
,
Salmonella typhi
,
Bacillus cereus,
Staphylococcus aureus
,
Candida albicans
and
Aspergillus flavus
.
Methanolic extract showed more antimicrobial activity than the other extracts. The results
indicated that
Bacillus cereus
and
Aspergillus flavus
were the most sensitive
microorganisms, showing the largest inhibition zones and the lowest MIC values. The least
antimicrobial activity was recorded against
Escherichia coli
(45).
The antibacterial activity of aqueous extract of
Foeniculum vulgare
was studied
against
E. coli, Klepsiella spp. and Pseudomonas spp
. The aqueous extracts of
Foeniculum
vulgare
showed antibacterial activity, it inhibited the coliform and
Klebsiella
spp (70).
The essential oils of the fruits of and
Foeniculum vulgare
Miller var.
vulgare
(Miller)
were assayed
in vitro
for antibacterial activity against
Escherichia coli
and
Bacillus
megaterium
, bacteria routinely used for comparison in the antimicrobial assays, and 27
phytopathogenic bacterial species and two mycopathogenes responsible for cultivated
mushroom diseases. A significant antibacterial activity, as determined with the agar diffusion
method, was shown by
Foeniculum vulgare
var.
vulgare
oil (71).
Essential oil was investigated for its antibacterial and antifungal activity against
seven infectious microbial pathogens,
Escherichia coli
(ATCC 25922),
Bacillus cereus
(ATCC
11778),
Lactobacillus acidophilus
(ATCC 53103),
Micrococcus luteus
(ATCC 9341),
Staphylococcus aureus
(ATCC 25923),
Klebsiella pneumoniae
(ATCC 15380) and
Streptococcus pneumoniae
(ATCC 12755), as well as
Aspergillus niger
,
Candida albicans
and
Rhizopus stolonifer
. The
Foeniculum vulgare
essential oil showed the diameter of
inhibition zone (DIZ) ranging from 19.4 ± 0.07 - 26.4 ± 0.09 mm at a concentration of 28
μg/disc in all the ten tested strains. The minimum inhibitory concentration (MIC) of essential
oil against bacterial and fungal strains was obtained in the range of 7.0 - 56 μg/ml (51).
The antibacterial effects of the ethanolic fruit extract were studied against
Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa
and
Proteus vulgaris.
The plant extract prevented the growth of
Staphylococcus aureus
and
Bacillus subtilis
. The minimum inhibitory concentration was found to be similar for both
microorganisms (1 mg/ml). Other tested organisms were not affected at any of the
concentrations used (39).
The antimicrobial effect of organic and aqueous leaves extracts of
Foeniculum
vulgare
was studied against
Staphylococcus aureus
,
Pseudomonas aeruginosa
,
Enterococcus hirea
,
Escherichia coli
and
Candida albicans
. All extracts of
Foeniculum
vulgare
showed antibacterial activity against all the tested microorganisms. The most
significant and active extract, were methanol and ethyl acetate against all the tested
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bacteria in comparaison to the hexane and aqueous extracts. On the other hand, the results
of antifungal activity of aqueous extract was better than the hexane and dichloromethane
extracts against
Candida albicans
(ATCC and CBS) (MIC = 0.78 mg/ ml). It appear that
C.
albicans
ATCC was the least susceptible microorganisms to the ethyl acetate extract (72).
The antifungal effects of
Foeniculum vulgare
were studied against
Aspergillus niger
, Aspergillus flavus
and
Fusarium graminearum
.
Foeniculum vulgare
showed antifungal
activity at a dose of 4 µl. Moreover, with the using food poison technique, the volatile
oil and extract5both showed good to moderate zone of inhibition (50).
The
in vitro
antifungal activity of
Foeniculum vulgare
essential oils was
investigated against three
Candida albicans
strains of different origin using disc and well-
diffusion and microdilution method, and compared to Nystatine and Fluconazole as standard
anti-mycotics. The results indicated that the studied essential oils showed antifungal activity
against all the isolates of
C. albicans
(MIC values:0.06mg/ml - 0.23mg/ml) (73).
Antiparasitic effects:
The larvicidal activity of the essential oils and its major constituents were evaluated
against third instar larvae of
Aedes aegypti
for 24 h. Pure compounds, such as limonene
isomers, were also assayed. The lethal concentrations LC50, C90 and LC99 were determined
by probit analysis using mortality rates of bioassays. A 99% mortality of
Ae. aegypti
larvae
was estimated at 37.1 and 52.4 µl/l of fennel essential oils from Cape Verde and Portugal,
respectively(48).
The repellent activity of (+)-fenchone and (E)-9-octadecenoic acid was tested against
Aedes aegypti
females using skin and patch tests in comparison with the commercial
repellent agent (N,N-diethylm-toluamide (DEET) and (Z)-9-octadecenoic acid). In a skin test
with female mosquitoes. (+)-Fenchone and (Z)-9-octadecenoic acid (0.4mg/cm2) exhibited
moderate repellent activity 30 min after treatment(74).
The larvicidal activity of essential oils was investigated against malaria vector,
Anopheles stephensi
. Of oils of three plants,
Foeniculum vulgare
oil was the most effective
against
A. stephensi
with LC50 and LC90 values of 20.10 and 44.51 ppm, respectively(75).
The essential oil of the leaves, flowers, and roots of
Foeniculum vulgare
exerted
larvicidal activity against fourth-instar larvae of the mosquito
Culex pipiens molestus
.
Terpineol and 1,8-cineole content of
Foeniculum vulgare
were the most effective contents
against
Culex pipiensmolestus
bites offering complete protection for 1.6 and 2 h,
respectively(76).
Antidiabetic effect:
The antiglycation properties of methanolic extracts of 23 fennel samples were
evaluated in the bovine serum albumin (BSA)/glucose system. The level of glycation,
conformational alterations and protein binding to RAGE receptors were assessed by Congo
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red binding assay and a brown staining method. Some samples showed high anti-glycative
activity(60).
Effect on reproductive system:
The anti-fertility effect of
Foeniculim vulgare
seed extract was studied in male rats.
Rat groups were orally administered 1 ml of hydro-alcoholic extract of fennel seed in four
doses of 35, 70, 140, and 280 mg/kg/bw daily for 60 days. After the last gavage, the rats
were anaesthetised and the caudal part of the right epididymis was used for sperm
counting. After fixation of the testes, microscopic sections were prepared and histological
changes were evaluated. The number of spermatogonia after doses of 140 and 280 mg/kg
and Sertoli cells after a dose of 140 mg/kg decreased significantly as compared with the
control group (P < 0.05). The number of primary spermatocytes and sperm count decreased
significantly in the treated groups (70, 140, and 280 mg/kg) compared to the control group
(P < 0.05). Furthermore, thickening of the basement membrane, cell apoptosis, and irregular
arrangement of the germinal epithelium were observed in the treated groups(77).
The compound anol or anethole, the major active compound of fennel oil, is
considered to be an active estrogenic agent due to its structural resemblance to
diethylstilbesterol, a synthetic estrogen. The effect of acetone extracts of
Foeniculum
vulgare
seeds at different dose levels (50, 150 and 250ug/100gm bw) was investigated on
mammary glands and oviducts of castrated rats. The extract was found to increase nucleic
acids and protein concentration as well as the organ weights in both tissues. The medium
and high doses were very effective. The results confirmed the estrogenic nature of the seed
extract(78).
The essential oil of fennel seeds (500, 750, 1000 mg/kg for 30 days) was
investigated for its and anti-osteoporotic activities in ovariectomized rat osteoporosis model.
The findings (assessed on the basis of bone mineral density and uterine weight) showed
that the fennel essential oil has a preventive effect on development of osteoporosis in
ovariectomized rats. This protective effect on early post-ovariectomy bone loss was dose
dependent and at the dose of 1000 mg/kg, it was even more than estradiol of 0.082±0.008
g cm2, P<0.05)(79).
The clinical efficacy of fennel extract was compared with echinophora-platyloba in
the primary dysmenorrhea. The clinical trial was carried out on sixty unmarried students with
mild and moderate dysmenorrhea in Shahrekord university of medical sciences. The severity
of pain was detected by the visual analogue scale during two cycles before and two cycles
after the intervention. There was no significant difference in the mean of dysmenorrhea
severity during the two cycles before the intervention between the two groups, but during
the two cycles after the intervention, both drugs could reduce the severity of dysmenorrheal
pain but fennel extract showed more significant (P<0.001) reduction (80).
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Antiinflammatory and analgesic effects:
The analgesic and anti-inflammatory action of the ethanolic extracts of
Foeniculum
vulgare
(50,100 and 200mgm/kg, ip ) was studied in
Wistar rats and Swiss Albino mice.
Analgesia was studied in Albino rats using formalin test and in Albino mice using writhing
test. Anti-inflammatory activity was investigated by carrageenan- induced hind paw edema.
The ethanolic extract produced significant (P<0.001) dose-dependent inhibition of pain
response elicited by acetic acid and formalin tests. It also exerted dose dependent
inhibition of edema development in the carrgeenan induced inflammation (42).
The antiinflammatory effect of the essential oil of
Foeniculum vulgare
was
investigated using the model of carrageenan induced rat paw edema. It showed anti-
inflammatory effect comparable to that of etodolac at 0.050 and 0.200 ml/kg doses (49).
The effects of
Foeniculum vulgare
extract in reduction of pain and other systemic
symptoms accompanying primary dysmenorrhea were studied using double-blind clinical trial
carried out on female students [90 (46 cases and 44 controls)] at Shahid Beheshti
University, Iran. Five capsules containing 46 mg of
Foeniculum vulgare
and identical
placebos were provided to be taken daily by the case and control groups respectively,
during the first three days following the onset of dysmenorrheal pain whenever they needed
the medications. The severity of pain in the treated group with
Foeniculum vulgare
extract,
showed a significant difference (P<0.001) in comparison with the placebo group, in addition
to significant differences in systemic symptoms (81).
The antinociceptive activities of some components of
Foeniculum vulgare
(alpha-
pinene, limonene, fenchone, trans-anethol and alpha-copaene) were investigated for
analgesic effects in mice using tail-flick tests. The drugs were injected intraperitoneally in
doses of 0.05, 0.1 and 0.2 ml/kg. Alpha-pinene and fenchone caused significant reduction in
the nociceptive threshold in the tail-flick test, while, other tested compounds showed no
significant analgesic effects (82).
The methanolic extract of the aerial parts of
Foeniculum vulgare
subsp.
piperitum
exhibited the highest antinociceptive activity at a dose level of 2000 mg/kg, while the activity
exhibited by the ethyl acetate extract was at (800 mg/kg). On the other hand,
n
-hexane
extract (700 mg/kg) and methylene chloride extract (500 mg/kg) exhibited similar
antinociceptive activities, being less than that of acetylsalicylic acid (200 mg/kg). The results
also revealed that the extracts under investigation exhibited significant anti-inflammatory
activity. The methanolic extract possessed the highest activity, where it significantly
decreased the weight of edema induced by carrageenan in the rat paw at dose levels of
1500 and 2000 mg/kg, it exerted a protective effect of 28 and 47%, respectively, compared
to the control value, while ibuprofen (35 mg/kg), used as a reference drug, exhibited a
protective effect of 52.23 % (47).
Crude ethanolic extracts of
Foeniculum vulgare
seeds was investigated for
antinociceptive activity. Results showed that the dose of 298 mg/Kg, compared to the
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indomethacin pattern, led to a significant reduction in the number of abdominal writhings in
the animals (43).
The hot plate method was used to determine the analgesic activity of the plant .
Foeniculum vulgare
ethanolic fruit extract (500 mg/kg, orally) showed a moderate analgesic
activity that was significant after 90 (P<0.5)
and 150 minutes (P<0.0l) of its administration.
The observed analgesia was of higher magnitude at 150min than after 90min. The ethanolic
fruit extract similarly showed an antipyretic activity that was evident at 30 and 90 minutes
(P<0.0l) but not at 150 minutes(39).
Effect on osteogenesis:
The effects of
Foeniculum vulgare
extract on proliferation and osteogenesis progress
were studied in human mesenchymal stem cells. Results of MTT assay and alkaline
phosphatase activity revealed that
Foeniculum vulgare
extract, at range of 5 to 50 µg/ml,
positively affect cell proliferation and mineralization. The most proliferation and enzyme
activity were seen with dose of 5 µg/ml (83).
Bronchodilatory effects:
The bronchodilatory effects of
Foeniculum vulgare
(aqueous and ethanol extracts
and essential oil) were examined by using precontracted isolated tracheal chains of guinea
pig. The results indicated bronchodilatory effects of ethanol extract and essential oil of
Foeniculum vulgare
which was not due to inhibitory properties of the plant on muscarinic
and histamine H1 and/or an stimulatory effect on β2-adrenergic receptors (84).
Effect on glucoma:
A single drop application of aqueous extract of
Foeniculum vulgare
was evaluation
for oculohypotensive activity in experimental models of glaucoma. The evaluation of
oculohypotensive activity of
Foeniculum vulgare
was done in rabbits with normal intraocular
pressure (IOP) and with experimentally elevated IOP achieved with water loading and
steroid induced glaucoma models. The aqueous seed extract of
Foeniculum vulgare
exhibited 17.49, 21.16 and 22.03% reduction of intraocular pressure (IOP) in normotensive
rabbits at 0.3%, 0.6% and 1.2% (w/v) concentrations respectively. The 0.6% concentration
was evaluated in acute and chronic models of glaucoma. A maximum mean difference of
31.20% was observed between vehicle treated and extract treated eyes in water loading
model, and a maximum mean IOP lowering of 31.29% was observed in steroid induced
model of glaucoma (85).
Hepatoprotective and nephroprotective effects:
The potential protective effect of fennel essential oils was studied against carbon
tetrachloride (CCl4) induced fibrosis in rats. Administration of CCl4 (1.5ml/kg
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/kg bw ) intrapretoneally (ip) in olive oil (1:7 dilution) for 7 successive weeks
resulted in liver damage manifested by significant increase in serum AST, ALT, ALP,
decreased total protein and increased triglycerides, total cholesterol, LDL and decreased
HDL level. Rats treated orally with essential oil of
Foeniculum vulgare
(Fennel, 200
&400kg/bw) for 7 successive weeks showed a significant protection against induced increase
in serum liver enzyme (AST,ALT, ALP), restored total protein level and ameliorate the
increased triglycerides, total, cholesterol, LDL and decreased the HDL. These protective
effects were further confirmed by histopathological examination (86).
The effect of (whey protein) concentrate (WPC) (0.5g/kg/day) or fennel seed extract
(FSE) (200mg/ kg/day) was evaluated on paraoxonase-1 activity (PON1) and oxidative
stress in liver of tienilic acid (TA) treated rats. TA administration significantly increased ALT
and AST, total- and direct bilirubin levels, serum tumor necrosis factor-α and nitric oxide
levels. Furthermore, serum PON1, and hepatic reduced glutathione, glutathione-S-transferase
and Na+/K+-ATPase values were diminished with a significant rise in the level of hepatic
lipid peroxidation. Triglycerides, total- and LDL-cholesterol levels were significantly elevated,
while HDL-cholesterol was unchanged. The administration of either WPC or FSE to TA-
treated animals significantly protected the liver against the injurious effects of tienilic acid.
This appeared from the improvement of hepatic functions, atherogenic markers, Na+/K+-
ATPase activity, endogenous antioxidants and hepatic lipid peroxidation level; WPC showed
the strongest protection effect (87).
The nephroprotective effects of different oral doses of aqueous extract of
Foeniculum
vulgare
seeds 250 mg/kg,
Solanum nigrum
500 mg/kg fruit and their mixture (of 250 and
500 mg/kg/oral respectively ) were studied in gentamicin induced nephrotoxicity in albino
rabbits. All the treatments were continued for 21 days. Blood samples were taken from all
groups at day 21 to determine serum urea, creatinine, albumin, plasma malondialdehyde
and catalase. Histopathological parameters of kidneys were also examined at day 21.
Gentamicin induced oxidative stress and caused structural changes in the kidneys. The
aqueous extract of
Foeniculum vulgare
seeds,
Solanum nigrum
fruit and their mixture
significantly prevented renal damage by normalizing increased levels of renal markers.
Mixture of both plants at high doses exhibited the more nephroprotective and antioxidant
activities (88).
The renoprotective effect of the aqueous extract of
Foeniculum vulgare
(150 mg/kg
bw) was studied in experimental PCOS female rats. The mean values of blood urea
nitrogen in PCOS rats treated with low dose of extract of
Foeniculum vulgare
and estradiol
valerate and non-treated, was significantly (P<0.05) increased compared with non-PCOS
and PCOS rats treated with high dose of extract of
Foeniculum vulgare
(89).
The protective effect of fennel essential oil (250, 500, and 1000 mg/kg/day, for 10 days)
as a phytoestrogen source was studied against cisplatin -induced nephrotoxicity in rats.
The serum levels of blood urea nitrogen (BUN) and creatinine (Cr), kidney tissue damage
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score (KTDS), kidney weight (KW) and body weight changes in CDDP-treated groups
increased significantly (P < 0.05). Fennel essential oil did not reduce the BUN, Cr, KTDS,
KW and body weight. Also, the serum and tissue levels of nitrite were not altered
significantly by fennel essential oil (90).
Antimutagenic and anticancer effects:
The potential antimutagenic and cancer chemoprevention effects of the hot water
crude extract of sweet fennel (
Foeniculum vulgare
Mill.) seeds were evaluated in well known
genetic model organisms: mice and Drosophila, using mutagenicity, molecular and
biochemical assays. In mice, mitomycin C (MMC) was administered to mice as a positive
control alone before and after treatment with 5 or 0.5 mg/Kg bw or in combination with
fennel crude extract as acute (24h) and sub acute (5 consecutive days) doses, respectively.
Chromosomal aberration assay in mice bone marrow cells revealed slight insignificant effect
of fennel extract on aberrant mitosis rate, while it gave remarkable significant reduction of
the MMC induced chromosomal aberrations. This effect was found to be dose-dependent.
However, random amplified polymorphism of DNA (RAPD) showed clear variation between
different classes of treated and non treated animals against MMC treatment, which reflected
DNA protective effect of fennel extract. The serum uric acid, urea and creatinine (kidneys
function) and liver function (GOT and GPT activities) were slightly affected by MMC, which
were improved by the ingestion of fennel extract. In Drosophila, fennel extract significantly
decreased the frequency of cholchicine induced aneuploidy and chromosomal aberrations in
post and pre-treatments (91).
The apoptotic activity of crude methanolic
Foeniculum vulgare
leave ethanolic
extract was investigated in cervical cancer cell lines (HeLa). The induction of apoptosis
was determined by analyzing DNA fragmentation in cervical cancer cells treated with active
fraction of crude methanol extract using agarose gel electrophoresis. Fragmentation of the
DNA was observed at different plant sample concentrations. Morphological observations were
carried out and apoptosis body was observed at 125µg/ml of the extract.
Foeniculum
vulgare
induced apoptosis on cervical cancer cell line and inhibited cell proliferation through
DNA fragmentation (92).
The anticarcinogenic potential of anethole was studied in Ehrlich ascites tumour
(EAT) in the paw of Swiss albino mice. The results revealed that anethole increased the
survival time, reduce the tumour weight and volume and body weight of the EAT-bearing
mice. It caused a significant cytotoxic effect in EAT cells in the paw, reduced the levels of
nucleic acids and MDA, and increased NP-SH concentrations. The histopathological changes
observed after treatment with anethole were comparable to the standard cytotoxic drug,
cyclophosphamide. The results on the frequency of micronuclei and the ratio of
polychromatic erythrocytes to normochromatic erythrocytes showed anethole to be
mitodepressive and non-clastogenic in the femoral cells of mice (93).
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Antioxidant effect:
The effects of fennel extract ( 70% ethanol) at a dose of of 100 and 200 mg/kg for
5 days, interaperitoneally, on serum level of oxidative stress was studied in female mice.
Results revealed that fennel extract can decrease the serum level of oxidative factors in
female mice; the authors concluded that it can be introduced as a novel medicine for
treatment of infertility (94).
Many phenolic compounds (3- caffeoylquinic acid, 4-caffeoylquinic acid, 1.5-
Odicaffeoylquinicacid, rosmarinic acid, eriodictyol-7-Orutinoside, quercetin-3-O-galactoside,
kaempferol-3-Orutinoside, kaempferol-3-O-glucoside, hydroxylcinnamic acid derivatives,
flavonoid glycosides and flavonoid aglycones) isolated from the plants were antioxidants (46).
The antioxidant value of
Foeniculum vulgare
was evaluated by measuring peroxide
and thiobarbituric acid values for oil at fixed time intervals. Both, the volatile oil and extract
showed strong antioxidant activity in comparison with butylated hydroxyanisole (BHA) and
butylated hydroxytoluene (BHT). In addition, their inhibitory action on linoleic acid system
was confirmed by monitoring peroxide accumulation in emulsion during incubation through
ferric thiocyanate method (50).
The antioxidant activity of fennel oils was measured in terms of hydrogen donating
or radical scavenging ability, using the stable radical DPPH. Fennel oil showed radical
scavenging ability at all tested concentrations, DPPH % Inhibition 11.24-21.88, IC50: 45.89g/l.
Ferric reducing capacity of fennel oil was 0.19-0.37 mmol/l Trolox (44).
Dermatological effects:
The response of idiopathic hirsutism to topical
Foeniculum vulgare
extract cream
was evaluated clinically in a double blind study. 38 patients were treated with creams
containing 1%, 2% of
Foeniculum vulgare
extract and placebo. Hair diameter and rate of
growth were evaluated. The efficacy of treatment with the cream containing 2%
Foeniculum
vulgare
was better than the cream containing 1%
Foeniculum vulgare
and these two were
more potent than placebo. The mean values of hair diameter reduction was 7.8%, 18.3%
and -0.5% for patients receiving the creams containing 1%, 2% and 0% (placebo)
respectively (95).
The effect of fennel topical gel on mild to moderate idiopathic hirsutism was studied
by randomized, double-blind, placebo-controlled clinical trial using forty four women with mild
to moderate idiopathic hirsutism. The treated group received fennel gel 3% and the control
group received placebo. Measurements were performed at zero time and 24 weeks after
treatment. Hair thickness was similar between the two groups before intervention. The hair
thickness reduced from 97.9±31.5 to 75.6±26.7 micron in patients receiving fennel gel after
24 weeks (P<0.001). Four patients complained of itching (3 in treated group) and 4 patients
The chemical constituents and pharmacological effects of Foeniculum vulgare - A
review
99
complained of irritation and itching (3 in treated group). However, these differences were not
statistically significant (96).
The wound healing action of aqueous extract of
Foeniculum vulgare
(2% and 7%
ointment) was studied in rats using excision wound model. Vaseline was used as control
while Mupirocin was used as standard. Post treatment the % wound contraction and wound
area was measured on 4th, 8th, 12th and 16th day. The results revealed significant decrease
in wound area by ointment of aqueous extract of
Foeniculum vulgare
(97).
Antiallergic effect:
In order to establish the antiallergic effect of fruits of
Foeniculum vulgare
, the
inhibitory actions of the fruit on 5-lipoxgenase (5-LOX) and b-hexosaminidase release were
evaluated. The 70% ethanol extract considerably inhibited 5-LOX-catalyzed leukotriene
production from A23187-induced rat basophilic leukemia (RBL)-1 cells. The IC50 was 3.2
mg/ml. From this extract, 12 major compounds including sabinene, fenchone, g-terpinene, a-
pinene, limonene,
p
-anisylacetone,
p
-anisylaldehyde, estragole (4-allylanisole),
trans-
anethole,
scopoletin, bergapten and umbelliferone were isolated. It was found that several terpene
derivatives including g-terpinene and fenchone as well as phenylpropanoid,
trans-
anethole,
revealed the considerable inhibitory action of 5-LOX. In particular, the IC50 of
trans-
anethole
was 51.6 mM. In contrast, ethanol extract and the isolated compounds did not show
considerable inhibitory activity on the degranulation reaction of b-hexosaminidase release
from antigen-treated RBL-2H3 cells. Ethanol extract and
trans-
anethole showed significant
inhibition of arachidonic acid-induced ear edema in mice, by oral administration at doses of
100-400 mg/kg (98).
Cardiovascular effects:
The hypotensive effects of the water extract of
Foeniculum vulgare
were
investigated in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats
(WKY). Oral administration of
Foeniculum vulgare
extract lowered the systolic blood
pressure of SHR but not of WKY. In SHR,
Foeniculum vulgare
treatment increased water,
sodium and potassium excretion. Ex vivo as well as
in vitro
.
Foeniculum vulgare
extract
inhibited the contractile responses of rat aorta to noradrenaline which blocked by N-nitro-L-
arginine (99).
The fennel oil and the main component of the fennel oil (anethole) inhibited
arachidonic acid-, collagen-, ADP- and U46619-induced platelet aggregation (IC50 from 4 to
147 microg/ml). Anethole also prevented thrombin-induced clot retraction at concentrations
similar to fennel oil. The essential oil and anethole, tested in rat aorta with or without
endothelium, displayed comparable NO-independent vasorelaxant activity at the same
antiplatelet concentrations which have been proved to be free from cytotoxic effects
in vitro
.
In vivo
, both
Foeniculum vulgare
essential oil and anethole orally administered in a subacute
The chemical constituents and pharmacological effects of Foeniculum vulgare - A
review
100
treatment to mice (30 mg/kg/day for 5 days) showed significant antithrombotic activity
preventing the paralysis induced by collagen-epinephrine intravenous injection (70% and
83% protection, respectively). At the antithrombotic dosage they were free from
prohemorrhagic side effect (62).
Hypolipidemic effect and effect on body weight:
The effect of
Foeniculum vulgare
fruit extracts in high fat diet and their possible role
in obesity and associated cardiovascular disorders were studied in rats. Three fractions
prepared by successive solvent technique from methanol extract of
Foeniculum vulgare
.
fruits were administered at a dose of 300 mg/bw by oral gavage and volatile oil obtained by
hydrodistillation at a dose of 0.2 ml/bw intraperitoneally once daily along with high fat diet
to the female albino rats for six weeks. Results revealed that body weight and fat pad
weights were reduced in extracts fed animals in a variable pattern. Cholesterol and
triglycerides levels, which were elevated in high fat diet fed animals, improved in a
significant manner. Maximum activity was observed with methanol fraction of the extracts
which contained maximum amount of phenolic (48.37 mg/g) and flavonoidal contents (21.44
mg/g) (100).
Toxicity and side effects:
The LD50 of
Foeniculum vulgare
essential oil was found to be 1.038 ml/kg (19).
However, acute oral toxicity study in female mice revealed that a single high dose
(2000 mg/kg) of the essential oil didn’t show loss of weight, autonomic behavioral changes
or other signs of toxicity. There was also no mortality observed in the study period,
suggesting that the LD50 (median lethal oral dose) of the essential oil is higher than
2000 mg/kg when given orally (55).
The plant extract lethality in mice was tested using three doses (0.5, 1 and 3g/kg, orally).
In addition, locomotor activity, bizarre reactions, sensitivity to sound, social interaction, tail
posture, aggressive behaviour, ataxia, paralysis, convulsions, tremors, prostration,
exophthalmos, pupil size, defaecation, salivation, urination, pattern of respiration, nasal
discharge, cyanosis and piloerection was observed over a period of 24 h. The plant extract
in doses of 0.5, 1 and 3 g/kg (orally) did not cause any deaths. Only the 3g/kg dose
showed signs of reduced locomotor activity and piloerection. Otherwise, all other parameters
were negative (9). No restrictions known for the seed used in infusions and preparations
containing an equivalent amount of the essential oil. It was not recommended during
pregnancy. No restrictions during lactation (101).
Dose:
5-7 g per day crushed or ground seeds were used as teas, tea-like products, and other
galenical preparations for internal use (101).
The chemical constituents and pharmacological effects of Foeniculum vulgare - A
review
101
II. CONCLUSION:
The review highlighted the chemical constituent, pharmacological and therapeutic effects of
Foeniculum vulgare
as promising source of drugs because of its safety and effectiveness.
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