Anethum graveolens / Dille

Dille kan wat betreft zijn medische kwaliteiten de pocketuitgave van venkel worden genoemd. Ook zijn uiterlijk heeft veel weg van venkel. Beide planten zijn geel bloeiend, hun bladeren zijn fijn vertakt en beide verspreiden een geur van anijs. '

Anethum graveolens betekent sterk ruikend. Culpeper beschrijft de geur onbegrijpelijk genoeg als onaangenaam en hij is niet de enige die er zo over dacht: een Oudhollandse volksnaam voor dille is stin­kende vinke, een verbastering van stinkende venkel, mét het Engelse 'strongsmelling fennel' weer een verwijzing naar de op­vallende gelijkenis tussen de twee planten. Toch geldt die ver­warring alleen de oppervlakkige beschouwer: de schermen van dille staan opgericht, die van venkel neigen wat voorover. Bovendien is venkel rijziger en meer vertakt, dille moet het meestal met één enkele stengel doen.

Dille is een éénjarige die zich moeilijk aanpast aan ongunstige omstandigheden. Een goed gedraineerde bodem op een zonnige plek is aan te raden. Er kan worden gezaaid in april en eventueel een tweede keer in juni. De plantjes kunnen niet worden verzet: het wortelstelsel is te teer om die ingreep te kunnen overleven. De uitgedunde borelingen kunnen in een salade of een saus wor­den verwerkt en de planten die mogen blijven hebben een speel­ruimte nodig van 30 cm.
Evenals zijn verwanten de anijs en de venkel werkt dille gunstig op de spijsvertering, gaat maagklachten tegen, 'stilt dat over-gheven' (Dodonaeus) en bestrijdt krampen en koliek. De olie van dillezaad bevat anethol, een krachtige stimulans met de werking van amfetamine, waarvan in lang vervlogen tijden al gebruik werd gemaakt: gladiatoren mengden dillezaad door hun voedsel bij wijze van doping; in Engeland werden zowel dille ­als venkelzaad kerkenzaadjes genoemd (meeting-seeds), naar de gewoonte er op te kauwen om tijdens de preek niet in slaap te vallen.

Rosetta Clarkson signaleerde in een medisch-botanisch handboek het gebruik van dille als middel tegen zwaarlijvig­heid : de 'patiënt' moest dan een bouillon drinken waarin het kruid was meegekookt. Hoewel deze toepassingen van dille als amfetamine dus wel voorkwamen, had venkel, de grote broer, als stimulans toch de meeste reputatie. Enigszins contradictorisch is dat dille ook wel als slaapmiddel gebruikt werd. Het kruid is daar zelfs naar vernoemd: dillan is een oudsaksisch woord voor in slaap wiegen, 


Dille verhoogt libido van mannen
Dille is al eeuwen in gebruik in de Europese en Zuid-Aziatische keuken, en traditionele genezers gebruiken thee van dillezaadjes wel eens als middel tegen slapeloosheid. Volgens een Thaise dierstudie verhoogt datzelfde dille ook de libido van mannen - en misschien ook hun testosteronspiegel.

Studie
Onderzoekers van de Thaise Khon Kaen University gaven mannelijke ratten gedurende 2 weken dagelijks dille-extract. Het humane equivalent van de doseringen die de onderzoekers gebruikten was ongeveer 0, 600, 1800 of 5400 milligram extract per dag. De onderzoekers laten weinig los over de aard van dat extract, behalve dat het was gefabriceerd door medewerkers van hun universiteit.

Resultaten
De onderzoekers plaatsten de behandelde ratten op dag 1, 7 en 14 in een kooi met geslachtsrijpe wijfjes, en monitoorden hun gedrag. Ze zagen dat de lichtste dosis extract op dag 1 en 7 het aantal keren verhoogde dat de ratten paarden met de wijfjes.
Na een paar dagen ebt het proseksuele effect van dille weg. Het extract had geen effect op de zaadkwaliteit van de ratten. Eerder hadden onderzoekers van Shiraz University in Iran in dierstudies wel degelijk een verminderde vruchtbaarheid van dille ontdekt, [Eur J Contracept Reprod Health Care. 2011 Dec;16(6):488-97.] maar dat betrof hogere doseringen dan de doses die de Thaise onderzoekers gebruikten.
 
Mechanisme
De onderzoekers weten niet precies hoe dille het seksuele gedrag van de ratten stimuleert. Ze vermoeden dat bioactieve stoffen in dille inwerken op de hersenen, en misschien ook de afgifte van testosteron verhogen. Dat laatste baseren de onderzoekers op de figuur hieronder. Hoe groter de witte vegen, des te meer tyrosine protein phosphorylation vonden de onderzoekers in de testes van de ratten. Dat is een merker voor enzymachtiviteit.
Welke enzymen door de toediening van dille-extract activeerd werden hebben de onderzoekers niet bepaald. Ze denken dat het gaat om enzymen die zijn betrokken bij de biosynthese van testosteron. De onderzoekers hebben evenmin in het bloed van de dieren de concentratie testosteron gemeten.

Dierstudie: dille verhoogt libido van mannen

Conclusie
"Anethum graveolens extract can enhance the mounting frequency and testicular protein phosphorylation in male rats", concluderen de onderzoekers. "This vegetable extract is not toxic to testes, epididymis, sperm production, or sperm physiology."
Bron: J Zhejiang Univ Sci B. 2013 Mar;14(3):247-52.


Pharmacogn Rev. 2010 Jul-Dec; 4(8): 179–184.
Anethum graveolens: An Indian traditional medicinal herb and spice
S. Jana and G. S. Shekhawat
Author information ► Article notes ► Copyright and License information ►

Anethum graveolens L. (dill) has been used in ayurvedic medicines since ancient times and it is a popular herb widely used as a spice and also yields essential oil. It is an aromatic and annual herb of apiaceae family. The Ayurvedic uses of dill seeds are carminative, stomachic and diuretic. There are various volatile components of dill seeds and herb; carvone being the predominant odorant of dill seed and α-phellandrene, limonene, dill ether, myristicin are the most important odorants of dill herb. Other compounds isolated from seeds are coumarins, flavonoids, phenolic acids and steroids. The main purpose of this review is to understand the significance of Anethum graveolens in ayurvedic medicines and non-medicinal purposes and emphasis can also be given to the enhancement of secondary metabolites of this medicinal plant.

INTRODUCTION
The genus name Anethum is derived from Greek word aneeson or aneeton, which means strong smelling. Its common use in Ayurvedic medicine is in abdominal discomfort, colic and for promoting digestion. Ayurvedic properties of shatapushpa are katu tikta rasa, usna virya, katu vipaka, laghu, tiksna and snigdha gunas. It cures ‘vata’, ‘kapha’, ulcers, abdominal pains, eye diseases and uterine pains. Charaka prescribed the paste of Linseed, castor seeds and shatapushpa (A. graveolens) pounded with milk for external applications in rheumatic and other swellings of joints. Kashyapa samhitaa attributed tonic, rejuvenating and intellect promoting properties to the herb (A. graveolens). It is used in Unani medicine in colic, digestive problem and also in gripe water.[1] Anethum graveolens L. is used in the preparations of more than 56 ayurvedic preparations, which include Dasmoolarishtam, Dhanwanthararishtam, Mrithasanjeevani, Saraswatharishtam, Gugguluthiktaquatham, Maharasnadi kashayam, Dhanwantharam quatham and so on.[2] Anethum graveolens L. (dill) believed to be the native of South-west Asia or South-east Europe.[3] It is indigenous to Mediterranean, southern USSR and Central Asia. Since Egyptian times, Anethum has been used as a condiment and also in medicinal purposes.[4] It was used by Egyptian doctors 5000 years ago and traces have been found in Roman ruins in Great Britain. In the Middle Ages it was thought to protect against witchcraft. Greeks covered their heads with dill leaves to induce sleep.


BOTANICAL DESCRIPTION
Anethum graveolens L. is the sole species of the genus Anethum, though classified by some botanists in the related genus Peucedanum as Peucedanum graveolens (L.).[5] A variant called east Indian dill or Sowa (Anethum graveoeloens var sowa Roxb. ex, Flem.) occurs in India and is cultivated for its foliage as a cold weather crop throughout the Indian sub-continent, Malaysian archipelago and Japan.

Anethum grows up to 90 cm tall, with slender stems and alternate leaves finally divided three or four times into pinnate sections slightly broader than similar leaves of fennel. The yellow flower develops into umbels.[6] The seeds are not true seeds. They are the halves of very small, dry fruits called schizocarps. Dill fruits are oval, compressed, winged about one-tenth inch wide, with three longitudinal ridges on the back and three dark lines or oil cells (vittae) between them and two on the flat surface. The taste of the fruits somewhat resembles caraway. The seeds are smaller, flatter and lighter than caraway and have a pleasant aromatic odor.

Cultivation
Dill prefers rich well-drained, loose soil and full sun. It tolerates a pH in the range 5.3 to 7.8. It requires warm to hot summers with huge sunshine levels; even partial shade will reduce the yield substantially. The plant quickly runs into seeds in dry weather. It often self sows when growing in a suitable position. Propagation is through seeds.[5] Seeds are viable for 3–10 years. The seed is harvested by cutting the flower heads off the stalks when the seed is beginning to ripe [Figure 1].


Ecological importance of the species
The herb is a good companion for corn, cabbage, lettuce and onions but inhibits growth of carrots. Dill reduces a carrot crop if it is grown to maturity near them. However, the young plant will help to deter carrot root fly. Sustainable production of fennel and dill by intercropping indicates that the presence of dill exerted a stabilizing effect on fennel seed yield. Insects, bees and wasps are attracted to the yellow flowers of Anethum for plant resources like nectar and pollens. Coriander and dill when planted together has a very remarkable pest control benefits.[7] Intercropping with flowering herbaceous plants increases parasitoid survivorship, fecundity and retention and pest suppression in agro ecosystems. Dill is potentially suitable host for parasitoids, Edovum puttleri Grissell, Cotesia glomerata and Pediobius foveolatus Crawford.[8,9]

Medicinal uses
Anethum is used as an ingredient in gripe water, given to relieve colic pain in babies and flatulence in young children.[5] The seed is aromatic, carminative, mildly diuretic, galactogogue, stimulant and stomachic.[10,11] The essential oil in the seed relieves intestinal spasms and griping, helping to settle colic.[12,13] The carminative volatile oil improves appetite, relieves gas and aids digestion. Chewing the seeds improves bad breath. Anethum stimulates milk flow in lactating mothers, and is often given to cattles for this reason. It also cures urinary complaints, piles and mental disorders.[14]

Other applications and importance
Anethum seeds are used as a spice and its fresh and dried leaves called dill weed are used as condiment and tea. The aromatic herb is commonly used for flavoring and seasoning of various foods such as pickles, salads, sauces and soups.[15,16] Fresh or dried leaves are used for boiled or fried meats and fish, in sandwiches and fish sauces. It is also an essential ingredient of sour vinegar. Dill oil is extracted from seeds, leaves and stems, which contains an essential oil used as flavoring in food industry. It is used in perfumery to aromatize detergents and soaps and as a substitute for caraway oil.[17] Anethum is used as a preservative as it inhibits the growth of several bacteria like Staphylococcus, Streptococcus, Escherichia coli and Pseudomonas. Compounds of dill when added to insecticides have increased the effectiveness of insecticides. Essential oil of A. graveolens L. is used as repellent and toxic to growing larvae and adults of Tribolium castaneum, wheat flour insect pest.[18] In doses of 60 minims, anethole is a fairly potent vermicide for hookworm.[19]

PHARMACOLOGY
Several experimental investigations have been undertaken in diverse in vitro and in vivo models. Some pharmacological effects of Anethum graveolens have been reported such as antimicrobial[14,20,21] antihyperlipidemic and antihypercholesterolemic activities.[22]

Seed extracts of A. graveolens L. have significant mucosal protective, antisecretory and anti-ulcer activities against HCl- and ethanol-induced stomach lesions in mice.[23] Two flavonoids have been isolated from A. graveolens L. seed, quercetin and isoharmentin, which have antioxidant activity and could counteract with free radicals. This effect may help to prevent peptic ulcer.[24,25] Dill fruit hydrochloric extract is a potent relaxant of contractions induced by a variety of spasmogens in rat ileum, so it supports the use of dill fruit in traditional medicine for gastrointestinal disorders.[26] Crude extracts of A. graveolens L. besides having strong anti-hyperlipidemic effects can also improve the biological antioxidant status by reducing lipid peroxidation in liver and modulating the activities of antioxidant enzymes in rats fed with high fat diet.[27]

It has been reported that aqueous extracts of A. graveolens showed a broad-spectrum antibacterial activity against S. aureus, E. coli, P. aeruginosa, S. typhimurium, Shigella flexneri and Salmonella typhii.[28] The higher activity of extract can be explained on the basis of the chemical structure of their major constituents such as dillapiole and anethole, which have aromatic nucleus containing polar functional group that is known to form hydrogen bonds with active sites of the target enzyme.[29]

CONSTITUENTS
Qualitative phytochemical analysis of the crude powder of plant parts collected was determined as reported in.[30] The phytochemical screening of plant showed that leaves, stems and roots were rich in tannins, terpenoids, cardiac glycosides and flavonoids [Table 1].

METABOLITES OF IMPORTANCE
Various different compounds have been isolated from the seeds, leaves and inflorescence of this plant; 17 volatile compounds have been identified. The main constituents of dill oil which is pale yellow in color, darkens on keeping, with the odor of the fruit and a hot, acrid taste are a mixture of a paraffin hydrocarbon and 40 to 60% of d-carvone (23.1%) with d-limonene (45%). It also consists of α-phellandrene, eugenol, anethole, flavonoids, coumarins, triterpenes, phenolic acids and umbelliferones. The fruit yields about 3.5% of the oil; its specific gravity varies between 0.895 and 0.915.

MOLECULES OF INTEREST: CARVONE AND LIMONENE
Carvone and limonene are monoterpenes, which are present as main constituent of dill oil from fruits.[31] α-phellandrene, dill ether and myristicin are the compounds, which form the important odor of dill herb.[15,32] Monoterpenes are 10-carbon members of the isoprenoid family of natural products; they are widespread in the plant kingdom and are often responsible for the characteristic odors of plants. These substances are believed to function principally in ecological roles, serving as herbivore-feeding deterrents, antifungal defenses and attractants for pollinators.[33] Seventeen compounds have been identified in Indian dill leaf.[34] The several applications of carvone are as fragrance and flavor, potato sprouting inhibitor,[35] antimicrobial agent and building block and biochemical environment. D-limonene is one of the most common terpenes in nature. It is a major constituent in several citrus oils (orange, lemon) being an excellent solvent of cholesterol; d-limonene has been used clinically to dissolve cholesterol-containing gallstones. It has chemopreventive and chemotherapeutic activities and also reported to have low toxicity in pre-clinical studies.[36] Myristicin is a naturally occurring insecticide and an important compound of essential oil.[12,37] Anethole is a terpenoid that is present in minor quantity in Anethum, but is also found in essential oil of anise and fennel.[38] It is used as a flavoring substance. p-anisaldehyde has a strong aroma and is an important component in pharmaceuticals and perfumery.

METABOLIC PATHWAY FOR CARVONE SYNTHESIS
The essential oils are primarily composed of mono and sesquiterpenes and aromatic polypropanoids synthesized via the mevalonic acid pathway for terpenes and the shikimic acid pathway for aromatic polypropanoids. The biosynthesis of the monoterpenes limonene and carvone proceeds from geranyl diphosphate via a three-step pathway. First, geranyl diphosphate is cyclized to d-limonene by limonene synthase. Secondly, this intermediate is stored in essential oil ducts without further metabolism or is converted by limonene 6-hydroxylase to trans-carveol. Finally trans-carveol is oxidized by a dehydrogenase to d-carvone[33].

CONSERVATION STATUS
To prevent extinction and derive maximum benefits from the indigenous plants of a nation, it is necessary to preserve the germplasm. Due to lack of proper cultivation practices, destruction of plant habitats and illegal and indiscriminate collection of plants from these habitats, many medicinal plants are severely threatened. Anethum seeds are exported to European countries, as they have been used tremendously in flavoring and pharmaceutical industries. Most of the pickle and perfumery industries as well as aromatherapies are highly dependent on the supply of its herb oil and seeds. The International Trade Centre has brought out a material survey of four west European countries (France, UK, The Netherlands and Germany) estimating an overall demand of freeze-dry herb to be less than 300 tonnes per annum to meet its industrial demand.

The plant is propagated through seeds. An increasing interest in the use of efficient protocols for the tissue culture and micropropagation for in vitro production of secondary metabolites and for clonal multiplication of elite genotypes has developed. Sharma et al.[39] have reported a complete protocol on micropropagation of Anethum graveolens L. through axillary shoot proliferation. Sehgal[40] studied the differentiation of shoot buds and embryoids from inflorescence of Anethum graveolens culture, which eventually formed normal plantlets. Very less in vitro research has been performed on this potential plant species. It is cultivated commercially throughout the country and most parts of Europe.

CONCLUSION AND FUTURE PROSPECTS
One of the serious problems in Apiaceae member is low seed set, which is due to the presence of male flowers, underdeveloped flowers and lack of proper pollination and fertilization.[40] Conventional breeding methods have met with limited success in improving this species. Tissue culture techniques used for propagation and conservation of several medicinal plants may prove useful for multiplication and improvement for this species as well.[39,41] The commercial importance of monoterpenes as flavorings, fragrances and pharmaceuticals has stimulated many efforts to increase their yield in plants through in vitro technology. At the same time, with the help of suspension culture, several physiological and biochemical parameters could be analyzed that are still not known in this commercially important plant species. Powerful techniques in plant cell and tissue culture, RDT, bioprocess technologies and so on, coupled with most sophisticated analytical tools such as NMR, HPLC; GC-MS, LC-MS etc. have offered mankind the great potency of exploiting the totipotent biosynthetic and biotransformation capabilities of plant cells under in vitro conditions.[42] Cell and tissue culture techniques of plants provide alternative research material, especially for development and metabolic studies that might be difficult to conduct in intact plants. So there is much scope to enhance the secondary metabolites of this plant.[46]

ACKNOWLEDGMENTS
G. S. Shekhawat acknowledges financial support from the University Grants Commission (UGC), New Delhi and Professor Aditya Shastri, Vice chancellor, Banasthali University for his unwavering support.

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The genus name Anethum is derived from Greek word aneeson or aneeton, which means strong smelling. Its common use in Ayurvedic medicine is in abdominal discomfort, colic and for promoting digestion. Ayurvedic properties of shatapushpa are katu tikta rasa, usna virya, katu vipaka, laghu, tiksna and snigdha gunas. It cures ‘vata’, ‘kapha’, ulcers, abdominal pains, eye diseases and uterine pains. Charaka prescribed the paste of Linseed, castor seeds and shatapushpa (A. graveolens) pounded with milk for external applications in rheumatic and other swellings of joints. Kashyapa samhitaa attributed tonic, rejuvenating and intellect promoting properties to the herb (A. graveolens). It is used in Unani medicine in colic, digestive problem and also in gripe water. Anethum graveolens L. is used in the preparations of more than 56 ayurvedic preparations, which include Dasmoolarishtam, Dhanwanthararishtam, Mrithasanjeevani, Saraswatharishtam, Gugguluthiktaquatham, Maharasnadi kashayam, Dhanwantharam quatham and so on. Anethum graveolens L. (dill) believed to be the native of South-west Asia or South-east Europe. It is indigenous to Mediterranean, southern USSR and Central Asia. Since Egyptian times, Anethum has been used as a condiment and also in medicinal purposes. It was used by Egyptian doctors 5000 years ago and traces have been found in Roman ruins in Great Britain. In the Middle Ages it was thought to protect against witchcraft. Greeks covered their heads with dill leaves to induce sleep.



Effects of Anethum graveolens L. seed extracts on experimental gastric irritation models in mice
BMC Pharmacology 2002, 2:21 doi:10.1186/1471-2210-2-21http://www.biomedcentral.com/1471-2210/2/21

Abstract
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.

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.



Materials and Methods
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].

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).

References

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Ind J Hosp Pharm 1978, 15:166-168.
Delaquis PJ, Stanich K, Girard B, Mazza G: Antimicrobial activity of individual and mixed fractions of dill, cilantro, coriander and eucalyptus essential oils.
Int J Food Microb 2002, 74:101-109. Publisher Full Text
Yazdanparast R, Alavi M: Antihyperlipidaemic and antihypercholesterolaemic effects of Anethum graveolens leaves after the removal of furocoumarins.
Cytobios 2001, 105:185-191. PubMed Abstract
Duke JA: Handbooke of Medical Herbs.
CRC Press, London 2001, 42.
Fleming T: PDR for Herbal Medicines.
Medical Economics Company, New Jersy 2000, 252-253.
Loomis TA: Essential of Toxicology.
Lea and Febiger, Philladelphia 1968, 67-78.
Bouwmeester HJ, Davies JAR, Toxopeus H: Enantiomeric composition of carvone, limonene, and carveols in seeds of dill and annual and biennial caraway varieties.
J Agricul Food Chem 1995, 43:3057-3064.
Faber B, Bangert K, Mosandl A: GC-IRMS and enantioselective analysis in biochemical studies in dill (Anethum graveolens L.).
Flav Frag J 1997, 12:305-314. Publisher Full Text
Matsunaga T, Hasegawa C, Kawasuji T, Suzuki H, Saito H, Sagioka , Tadashi , Takahashi R, Tsukamoto H, Morikawa T, Akiyama T: Isolation of the antiulcer compound in essential oil from the leaves of Cryptomeria japonica.
Biol Pharmac Bull 2000, 23:595-598.
Hiruma-Lima CA, Gracioso JS, Toma W, Almeida AB, Paula ACB, Brasil DSB, Muller AH, Souza-Brito ARM: Gastroprotective effect of aparisthman, a diterpene isolated from Aparisthmium cordatum, on experimental gastric ulcer models in rats and mice.
Phytomedicine 2001, 8:94-100. PubMed Abstract
Alarcon de la Lastra C, Martin MJ, La-Casa C, Motilva V: Antiulcerogenicity of the flavonoid fraction from Bidens aurea: comparison with ranitidine and omeprazole.
J Ethnopharmacol 1994, 42:161-168. PubMed Abstract | Publisher Full Text
Reyes M, Martin C, Alarcon de la Lastra C, Trujillo J, Toro MV, Ayuso J:Antiulcerogenicity of the flavonoid fraction from Erica andevalensis Cabezudo-Rivera.
Z fuer Naturforschung, J Bioscie 1996, 51:563-569.
Alvarez A, Pomar F, Sevilla MA, Montero MJ: Gastric antisecretory and antiulcer activities of an ethanolic extract of Bidens pilosa L. var. radiata Schult. Bip.
J Ethnopharmacol 1999, 67:333-340. PubMed Abstract | Publisher Full Text
Gonzales E, Iglesias I, Carretero E, Villar A: Gastric cytoprotection of Bolivian medicinal plants.
J Ethnopharmacol 2000, 70:329-333. PubMed Abstract | Publisher Full Text
Moehle B, Heller W, Wellmann E: UV-induced biosynthesis of quercetin 3-o-beta-d-glucuronide in dill Anethum graveolens cell cultures.
Phytochemistry 1985, 24:465-468. Publisher Full Text
Mahran GH, Kadry HA, Thabet CK, Al-Azizi MM, Liv N: GC/MS analysis of volatile oil of fruits of Anethum graveolens.
Int J Pharmacog 1992, 30:139-144.
Mizui T, Doteuchi M: Effect of polyamines on acidified ethanol-induced gastric lesions in rats.
Jap J Pharmacol 1983, 33:930-945.
Sun X-B, Matsumoto T, Kiyohara H: Cytoprotective activity of peptic polysaccharides from the root of Panax ginseng.
J Ethnopharmacol 1991, 31:101-107. PubMed Abstract | Publisher Full Text
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Phytother Res. 2006 Oct;20(10):865-8.The effects of Anethum graveolens L. on female reproductive system.
Monsefi M1, Ghasemi M, Bahaoddini A.

The effects of Anethum graveolens L. (dill) extracts on the female reproductive system were studied in 54 Wistar female rats with regular estrous cycle in six groups. The experimental groups were fed with 0.045 g/kg and 0.45 g/kg of aqueous extract, 0.5 g/kg and 5 g/kg of ethanol extract for 10 days. The sham group was fed with solvent and the controls received no treatment. The estrous cycle changes were determined by daily vaginal smear changes. At the beginning and at the end of the experiment blood samples were provided to determine the blood estradiol and progesterone concentration. The ovaries were prepared histologically and the volume of different follicles was estimated. A significant increase was observed in the duration of the estrous cycle and in the diestrus phase and the progesterone concentration in high dose extract treatment. The stereological study did not reveal any significant changes in the volumes of ovaries, primary, secondary and graafian follicles. Dill can be used either as a regulatory agent of the menstrual cycle for women with irregular cycles or as an antifertility agent. More studies are needed to clarify the properties of this herb.


Eur J Contracept Reprod Health Care. 2011 Dec;16(6):488-97. doi: 10.3109/13625187.2011.622815.
Effects of Anethum graveolens L. on fertility in male rats. Monsefi M1, Zahmati M, Masoudi M, Javidnia K.

OBJECTIVES:
The effects of Anethum graveolens seed extract on fertility of male rats were investigated.
METHODS:
Male Wistar rats were divided into five groups according to the treatment they received during 42 days: control, low dose (0.5 g/kg) and high dose (5 g/kg) of aqueous extracts, and low dose (0.045 g/kg) and high dose (0.45 g/kg) of ethanol extracts of Anethum graveolens seed. Sperm count and motility and testosterone concentration were measured. Sections of the testes, epididymis, and seminal vesicles were stained with peroxidase-conjugated lectins of Ulex europaeus agglutinin, peanut agglutinin, Dolichos biflorus agglutinin, soy bean agglutinin and concanavalin A. The treated male rats were mated with females and the crown-rump lengths and weights of their newborn pups were measured.
RESULTS:
No significant differences in sperm count, sperm motility or testosterone concentration were observed in the experimental groups. However, female rats did not become pregnant after mating with rats given the high dose of the ethanol extract. The distribution of terminal sugars on the epithelial surface of the reproductive structures decreased in the experimental groups.
CONCLUSION:
Anethum graveolens extract decreased fertility rate by modifying some terminal sugars on the cell surface of male reproductive organs involved in sperm maturation, capacitation and oocyte recognition.


Phytother Res. 2008 Dec;22(12):1695-7. doi: 10.1002/ptr.2553.
The effect of Anethum graveolens L. (dill) on corticosteroid induced diabetes mellitus: involvement of thyroid hormones. Panda S.

An investigation was made to evaluate the role of Anethum graveolens L. (dill) leaf extract in the regulation of corticosteroid-induced type 2 diabetes mellitus in female rats. In dexamethasone-treated animals (1 mg/kg for 22 days) an increase in serum concentration of insulin and glucose and in hepatic lipid peroxidation (LPO) was observed. However, there was a decrease in serum concentration of thyroid hormones and in the endogenous antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) in liver. In animals treated with an equivalent amount of dexamethasone for a similar period (22 days) when received the leaf extract (100 mg/kg b.wt/d.) for last 15 days a decrease in the concentration of both serum glucose and insulin was observed, indicating the potential of the plant extract in the regulation of corticosteroid-induced diabetes. Dexamethasone-induced alterations in the levels of thyroid hormones as well as in hepatic LPO, SOD, CAT and GSH were also reversed by the plant extract.



Info over de etherische olie van DILLE    -  ANETHUM GRAVEOLENS

Farmacologische werking etherische olie uit het zaad:
Anticatarraal, ademhalingswegen – anticoagulant (infarct, hemogliase) – bactericidal – bronchitis - carminatief – cholagoog – choleretisch – constipatie - digestief – dyspepsie – hypotensor, hypotensie – mucolytisch – sedatief – slapeloosheid, slaapstoornissen – spasmolytisch, spasmen van de gladde spieren (koliek, hik).

De etherische olie in grote hoeveelheden kan neurotoxisch en abortief en niet voor baby’s, kinderen en zwangere. (Franchomme & Penoel 2001 p.351). De chemische samenstelling van de olie lijkt veel op die van karwij (carvon + limoneen).

Therapeutische werking: 
anticoagulans+ - antiseptisch – bloeddrukverlagend -  bronchitis, catarale -  carminatief -     cholagogum+++    -   digestief   -    diuretisch (licht) - galactogogum  -  gebrek aan eetlust -  halitose (zaden kauwen) - hemogliase+,infarctus risico verminderend  - hik -  koliek  -  krampstillend  -  leverinsufficiëntie - maag- en darmstoornissen - menstruatiestoornissen - ontstekingwerend, slijmvliezen+++ -  oorpijn  -   sedatief -  slapeloosheid - slijmoplossend+++-spijsverteringbevorderend+ - stimulerend  -  stomachisch  -  tonisch, voor de spijsvertering - wormdrijvend. De zaden bevatten een olie die een kalmerend effect heeft op spieren die digestief werkzaam zijn. Thee heeft een slaapverwekkend effect en dille bevat veel  mineralen, flavonoïden en vitamine C.
Contra indicatie:

Niet gebruiken bij baby’s, kinderen en zwangere vrouwen. Bij een overdosis: neurotoxisch en abortief. Verder niet toxisch, niet irritant. Fotosensibiliserend, kan dermatitis veroorzaken, maar niet bij een normale dosering (Tisserand & Ballacs 1995b p.204). Blaartrekkend.



ANETH Pharmacopée française 1993
Anethum graveolens
La partie utilisée de l’aneth est constituée par le fruit séché d’Anethum graveolens L. L’aneth
contient au minimum 2,5 pour cent V/m d’huile essentielle.

CARACTÈRES
L’aneth a une odeur caractéristique.
Le fruit, ovoïde, elliptique, est constitué de 2 méricarpes se disjoignant facilement. Chaque
méricarpe, brun, glabre, mesure environ 3 mm à 4 mm de long, 2 mm à 3 mm de large et 1 mm
d’épaisseur. La face convexe, fortement comprimée, est caractérisée par 3 côtes dorsales
saillantes, filiformes, jaunâtres et par 2 côtes latérales dilatées en ailes minces, jaune clair. Sur la
face commissurale, deux bandes brun foncé, correspondant aux éléments sécréteurs, sont
nettement visibles.
Examinée au microscope, la section transversale présente une face dorsale convexe à 3 côtes peu
marquées et à 2 côtes latérales nettement allongées. L’épicarpe est formé de cellules
cuticularisées, rectangulaires, à parois cellulosiques fines. Le mésocarpe contient, au niveau de
chaque vallécule, une poche sécrétrice de très grande taille, dont les cellules sont colorées en brun
fauve, et, au niveau de chaque côte, un faisceau libéro-ligneux dont les vaisseaux sont entourés de
fibres à parois lignifiées. L’endocarpe est formé par une assise de cellules isodiamétriques, de
petite taille. L’albumen est constitué par des cellules polyédriques à parois cellulosiques épaissies
et à contenu huileux.
Examiné au microscope, en présence de réactif lactique R, l’aneth pulvérisé (300), brun, présente
des fragments d’épicarpe à cellules polyédriques de grande taille, à parois fines, cellulosiques,
recouvertes d’une cuticule finement striée et avec de rares stomates ; des fragments des assises
externes du mésocarpe formées de cellules polyédriques, à parois irrégulièrement épaissies,
canaliculées et présentant des diverticules internes ; ces fragments sont souvent associés à
l’épicarpe ; des fragments des assises internes du mésocarpe constituées de nombreuses cellules
allongées, à parois régulièrement épaissies et légèrement canaliculées ; des vaisseaux à
ornementations spiralées ou annelées, accompagnés de fibres lignifiées ; des fragments de
bandelettes sécrétrices à contenu rougeâtre ; des fragments d’endocarpe à cellules allongées, à
parois fines et légèrement sinueuses ; des fragments d’albumen dont les cellules, polyédriques, à
parois cellulosiques et épaissies, contiennent des gouttelettes d’huile.

IDENTIFICATION
A. L’aneth présente les caractères macroscopiques précédemment décrits.
B. Examiné au microscope, l’aneth pulvérisé (300) présente les caractères microscopiques
précédemment décrits.

ESSAI
Éléments étrangers (2.8.2). Le taux des éléments étrangers n’est pas supérieur à 2,0 pour cent.
Chromatographie de l’huile essentielle. Opérez par chromatographie sur couche mince (2.2.27)
en utilisant une plaque recouverte de gel de silice GF254 R.
Solution à examiner. Prélevez 0,1 mL du mélange huile essentielle-xylène obtenu au cours du
dosage et ajoutez 1,0 mL d’éthanol à 96 pour cent R.
Solution témoin. Dissolvez 0,01 mL de carvone R dans 1,0 mL d’éthanol à 96 pour cent R.
Déposez séparément sur la plaque, en bandes de 20 mm sur 3 mm, 1 µL, 2 µL et 5 µL de chaque
solution. Développez sur un parcours de 10 cm avec un mélange de 20 volumes d’hexane R et de
80 volumes de toluène R. Laissez sécher la plaque à l’air pendant quelques minutes. Examinez en
lumière ultraviolette à 254 nm. Le chromatogramme obtenu avec la solution à examiner présente
une bande d’atténuation de fluorescence, semblable quant à sa position, à la bande principale du
chromatogramme obtenu avec la solution témoin. Pulvérisez 5 mL environ de la solution d’aldéhyde
anisique R puis chauffez la plaque à 110 °C pendant 5 min. Examinez à la lumière du jour. Le
chromatogramme obtenu avec la solution à examiner présente plusieurs bandes dont une, rouge
brique, semblable quant à sa position et sa coloration, à la bande principale du chromatogramme
obtenu avec la solution témoin. Il présente également quatre bandes principales : une bleue, située
en dessous de la bande correspondant à la carvone et trois bandes, respectivement par ordre
croissant de Rf rose vif, brun et violet, situées au dessus de la bande correspondant à la carvone.
Les bandes rose et violette peuvent être de moindre intensité.
Teneur en eau (2.2.13). Déterminée par entraînement sur 20,0 g d’aneth, la teneur en eau n’est
pas supérieure à 10,0 pour cent.
Cendres totales (2.4.16). Déterminé sur 1,0 g d’aneth pulvérisé (710), le taux des cendres totales
n’est pas supérieur à 8,0 pour cent.

DOSAGE
Effectuez le dosage des huiles essentielles dans les drogues végétales (2.8.12). Utilisez 25 g d’aneth
contusé, un ballon de 1000 mL et 300 mL d’eau comme liquide d’entraînement. Introduisez 0,20 mL
de xylène R dans le tube gradué. Distillez à un débit de 3 mL à 4 mL par min pendant 4 h.

CONSERVATION
En récipient bien fermé, à l’abri de la lumière et de l’humidité. 






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