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Herb Of The Week - Dill - Effects of the seed extracts on experimental gastric irritation models in mice

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The reading is a bit dry, but I figured it may be of interest to some ..

 

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Chris (list mom)

 

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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=140031

 

Effects of Anethum graveolens L. seed extracts on experimental gastric

irritation models in mice

 

Hossein Hosseinzadeh,1 Gholam_Reza Karimi,2 and Maryam Ameri3

1Pharmaceutical Research Center and Department of Pharmacodynamy and

Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences

(MUMS), P.O.Box 91775-1365, Mashhad, Iran 2Department of Pharmacodynamy

and Toxicology, Faculty of Pharmacy, Mashhad University of Medical

Sciences (MUMS), P.O.Box 91775-1365, Mashhad, Iran 3Department of

Pharmacodynamy and Toxicology, Faculty of Pharmacy, Mashhad University

of Medical Sciences (MUMS), P.O.Box 91775-1365, Mashhad, Iran

 

Corresponding author.

Hossein Hosseinzadeh: hosseinzadehh; Gholam_Reza Karimi:

gho_karimi; Maryam Ameri: school-pharmacy

Received June 20, 2002; Accepted December 19, 2002.

 

Background

As a folk remedy, Anethum graveolens seed (dill) is used for some

gastrointestinal ailments. We aimed to evaluate aqueous and ethanolic

extracts of anti-ulcer and acute toxicity effects of the Anethum

graveolens in mice.

 

Results

Gastric mucosal lesions were induced by oral administration of HCl (1 N)

and absolute ethanol in mice. The acidity and total acid content of

gastric juice were measured in pylorus-ligated mice. LD50 values of the

aqueous and ethanolic extracts were 3.04 g/kg, i.p., (1.5, 6.16) and

6.98 g/kg, i.p., (5.69, 8.56), respectively. The efficacy of high dose

of extracts (p.o.) was similar to sucralfate. The acidity and total acid

content were reduced by the orally or intraperitoneally administration

of the extracts.

 

Conclusions

The results suggest that A. graveolens seed extracts have significant

mucosal protective and antisecretory effects of the gastric mucosa in

mice.

 

Background

Anethum graveolens L. (dill) is a sparse looking plant with feathery

leaves and tiny yellow flowers. Some pharmacological effects have been

reported, such as antimicrobial [1,2], antihyperlipidaemic and

antihypercholesterolaemic [3] activities. As a folk remedy, dill is

considered for some gastrointestinal ailments such as flatulence,

indigestion, stomachache and colic [4]. Dill fruit has an antispasmodic

effect on the smooth muscles of the gastrointestinal tract [5].

 

On the basis of above observations, the antisecretory and mucosal

protective effects of A. graveolens seed extracts were evaluated in

mice.

 

Results

The maximum non-fatal doses of aqueous and ethanolic extracts were 0.45

g/kg and 5 g/kg (i.p.), respectively. LD50 values of the aqueous and

ethanolic extracts were 3.04 g/kg, i.p. (1.5–6.16) and 6.98 g/kg, i.p.

(5.69–8.56), respectively.

 

The aqueous and ethanolic extracts of A. graveolens seed significantly

decreased the occurrence of gastric lesions induced by HCl (ED50 values

were 0.12 g/kg (0.18–7.88) and 1.12 g/kg (0.81–1.55), respectively) and

ethanol (ED50 values were 0.34 g/kg (0.26–0.43) and 1.73 g/kg

(0.43–7.05), respectively) (Tables 1,2,3,4). The potency ratio of the

aqueous extract versus the ethanolic extract was significant (P < 0.05).

At a high dose (5 g/kg), the protection of the ethanolic extract against

ethanol induced lesion was also equal to sucralfate (Table 4). All the

extracts showed anti-ulcer activity in a dose-dependent manner.

 

The oral and intraperitoneal administrations of both extracts induced a

significant decrease in total gastric acid together with an increase in

pH values (Tables 5,6,7,8). These effects were dose-dependent. Both

extracts with higher doses showed antisecretory activity as effective as

cimetidine. The ED50 values of the aqueous and ethanolic extracts oral

treatment were 0.17 g/kg (0.43–2.04) and 0.07 g/kg (0.03–0.15),

respectively. The ED50 values of the aqueous and ethanolic extracts

intraperitoneal treatment were 0.02 g/kg (0.01–0.03) and 0.03 g/kg

(0.01–0.08), respectively. The potency ratio of the aqueous extract

versus the ethanolic extract was not significant in these tests.

 

Discussion

These results indicate that the extracts of A. graveolens seed have

effective antisecretory and anti-ulcer activity against HCl- and

ethanol-induced stomach lesions.

 

In respect to LD50 values, the aqueous extract was more toxic than the

ethanolic extract. Compare with a toxicity classification [6], the

aqueous and ethanolic extracts are relatively and little toxic,

respectively. As high doses of ethanolic extract was used in this study,

in clinical trial the toxicity of dill should be considered.

 

The oral administration of the extracts diminished HCl-induced gastric

lesions in mice. This may be related to an antacid effect or

cytoprtotective properties in gastric mucus. The cytoprotective action

against ethanol showed that the effects of extracts are not a simple

acid neutralizing activity but the dill extracts have a cytoprotective

effect against the gastric mucosa in ethanol-induced gastric lesion in

mice.

 

It is possible that the inhibitory effects of extracts are due, at least

partly, to the presence of terpenes in dill [7,8]. Terpenes were

associated to antiulcerogenic activity in other plants [9,10]. Some

triterpenes are known as antiulcer drugs and their action has been

suggested to be due to the activation of cellular protection, reduction

of mucosal prostaglandins metabolism-cytoprotective action and reduction

of gastric vascular permeability [19]

 

Flavonoids have antiulcer and gastroprotective activities [11-13]. The

aqueous extracts of Phoradendron crassifolium and Franserio artemisiodes

that contain polyphenolic agents exerted cytoprotective activity in rats

[14]. Two flavonoids have been isolated from A. graveolens seed,

quercetin 3-O-beta-D-glucuronide and isoharmentin

3-O-beta-D-glucuronide, have antioxidant activity and could counteract

with free radicals. This effect may help to prevent ulcer peptic

[15,16].

 

The extracts provoked a marked decrease in total gastric acid together

with an increase in pH values. As the fruit of dill has an antispasmodic

effect on the smooth muscles of the gastrointestinal tract [5], it is

possible that both extracts act via cholinergic system (an

anticholinergic activity) and block release of HCl. At this stage, other

mechanisms such as H2 receptor antagonist effect or the inhibition of

gastric H+,K+-ATPase can not be excluded.

 

In respect to the ED50 values, the aqueous extract was more potent than

the ethanolic extract in HCl- or ethanol-induced stomach lesions.

However, both extracts showed similar potency in reduction total gastric

acid together with an increase in pH values. This may be related to the

extracts different mechanisms of action. The ED50 values of extracts

were much lower than their LD50 values.

 

In conclusion, A. graveolens seed markedly inhibits acid secretion and

the occurrence of lesions in stomach but exact mechanisms are not clear

yet and need further investigations.

 

Animals

Male albino BALB/c mice 25–35 g were obtained from the animal house of

School of Pharmacy, Mashhad University of Medical Sciences. Animals were

housed in colony room 12/12 hr light/dark cycle at 24 ± 1°C. After 24 h

fasting, the mice were used for the experiments but were allowed

drinking water during the 24 h fasting period. All animal experiments

were carried out in accordance with Mashhad University of Medical

Sciences, Ethical Committee acts.

 

Plant material

The seed was collected at Bojnord (a town in Khorassan province, the

northeastern of Iran). All samples collected were dried in shade and

then powdered. Ferdowsi University properly identified the plant and

voucher samples were preserved for reference in the herbarium of

Department of Pharmacognosy, School of Pharmacy, Mashhad (293-0107-18).

 

The preparation of extracts

The seed powder was extracted using maceration with ethanol (80 v/v) or

water for 3 days and, subsequently, the mixture was filtered and

concentrated under reduced pressure (by a rotaevaporator) at 40°C. The

yield (w/w) of the aqueous and ethanolic extracts was 6.46% and 8.5%,

respectively.

 

HCl or ethanol-induced mucosal membrane lesions

Gastric mucosal lesions were induced by the modified method of Mizui and

Doteuchi [17]. The mice were divided into groups of 6 animals. After 24

h fasting, the extracts and drugs were administered orally to the mice.

30 min thereafter, each mouse received 0.2 ml of 1 N HCl or absolute

ethanol by oral administration. 60 min after administration of the

necrotizing agent, each animal was killed by ether, and the stomach was

excised, inflated by injecting 2 ml of normal saline and then fixed for

30 min in 5% formalin solution. After opening along the greater

curvature, HCl induced gastric damage was observed in the gastric mucosa

as elongated black-red lines parallel to the long axis of the stomach of

the mice. The lesion index was determined as the sum of erosion length

per mouse [18]. Ethanol induced lesion was assessed and scored for

severity according to, (0) absence of lesion, (1) superficial 1–5

hemorrhagic points, (2) superficial 6–10 hemorrhagic points, (3)

submucosal hemorrhagic lesions with small erosions (4) severe

hemorrhagic lesion and some invasive lesions.

 

Antisecretory study

One hour after extract or test drug treatment, mice were anesthetized

(xylazine 10 mg/kg plus ketamine 100 mg/kg, i.p.) and the pylorus was

ligated. The animals were killed 3 h later and their stomach content was

drained into a tube which was centrifuged 2000 rpm for 10 min. The pH

was recorded with a digital pH meter. Total acid content of gastric

secretion was determined by titration against 0.05 N NaOH [19].

 

ED50 values

ED50 values and the corresponding confidence limits were determined by

the Litchfield and Wilcoxon method (PHARM/PCS Version 4).

 

Acute toxicity

Different doses of extracts were injected intraperitoneally into groups

of six mice. The number of death was counted at 24 h after treatment.

LD50 values and the corresponding confidence limits were determined by

the Litchfield and Wilcoxon method (PHARM/PCS Version 4).

 

Statistical analysis

The data were expressed as mean values ± S.E.M. and tested with analysis

of variance followed by the multiple comparison test of Tukey-Kramer.

Ethanol induced lesion was assessed by Dunn's test.

 

Acknowledgments

The authors are thankful to the Vice Chancellor of Research, Mashhad

University of Medical Sciences for financial support.

 

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