Journal of Tropical Medicine
Volume 2016 (2016), Article ID 1098916, 11 pages
http://dx.doi.org/10.1155/2016/1098916

Review Article

The Role of Anethum graveolens L. (Dill) in the Management of Diabetes

Mohammad Taghi Goodarzi,1,2 Iraj Khodadadi,¹ Heidar Tavilani,¹ and Ebrahim Abbasi Oshaghi¹

¹Department of Clinical Biochemistry, Medical School, Hamadan University of Medical Sciences, Hamadan, Iran
²Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

Received 17 August 2016; Accepted 20 September 2016

Academic Editor: Carlos E. P. Corbett

Copyright © 2016 Mohammad Taghi Goodarzi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Aim. There is evidence that Anethum graveolens (AG) has been used for centuries in Asian traditional medicine, and its constituents have useful effects on the control and management of diabetes and cardiovascular disorders. AG has many useful effects, including hypolipidemic and hypoglycemic effects, and it has been reported to reduce the incidence of diabetic complications. It acts mainly by affecting antioxidant capacity and change in some genes in glucose and lipid pathways. The aim of the present paper was to summarize pharmacological effects of AG in the management of diabetes. Methods. To prepare this review, a pharmacological and phytochemical literature survey was performed using Scopus, PubMed, and Web of Science. Also, some historical and ethnopharmacological literature sources were used. Results. This review plans to provide readers with an assessment of the pharmacological effects of AG, especially in diabetes. Conclusion. The paper highlights the therapeutic effects of AG which would aid in supporting their safe use in the management of diabetes and cardiovascular diseases.

1. Introduction

Diabetes mellitus is a chronic metabolic disorder that is distinguished by hyperglycemia, underutilization of blood glucose, and defects in the metabolism of macronutrients such as carbohydrates, fat, and protein, secondary to the disturbance in insulin action [1, 2]. Type 1 diabetes is caused as a result of insulin deficiency due to failure of pancreatic beta-cells. Therefore, diabetic patients need exogenous insulin injection, whereas patients with type 2, known as insulin independent, do not respond to insulin and consequently can be managed by lifestyle changes. Type 2 diabetes constitutes 90% of the diabetic cases in the world [3]. Next to cancer and heart disease, diabetes mellitus is the third most life-threatening disorder which has a high rate of morbidity and mortality worldwide. Prevalence of this disorder is quickly rising in every part of the world [4]. As a result, it is projected to affect 552 million people in 2030, rising sharply from 336 million in 2011 [3]. Signs of type 1 and 2 diabetes may include hyperglycemia, abnormal thirst, repeated urination, weight loss and severe hunger, nausea and vomiting, mood changes, and severe weakness and tiredness [1]. The purpose of this review was to identify Anethum graveolens L. (AG) as a valuable herbal plant, originating from Asian traditional medicine, in the management of diabetes. Conducted studies could allow representing the potential applications for future research. To complete the assumed task, traditional sources regarding the usage and the carried out investigation on Anethum graveolens L. are collected and explained. Essential assessments of the documented bioactive components particularly in terms of their correlation with recognized traditional use and current pharmacological knowledge are discussed. Phytochemical studies, antidiabetic properties, suggested mechanism, and the main compounds of AG that may be responsible for useful effects of AG are described too.

2. Materials and Methods

To prepare this review a pharmacological and phytochemical literature survey was performed using Scopus, PubMed, and Web of Science.

3. Results and Discussion

3.1. Blood Glucose and Lipid Profile in Diabetic Patients

Studies have shown that blood lipid peroxidation markedly rises in diabetes due to vascular injury, which is provoked by hyperglycemia and free radicals. This peroxidation can further aggravate the progress of diabetic complications and is thought to happen as a result of defects in insulin secretion by pancreatic β-cells. Diabetes also leads to an impaired lipid profile, including low levels of high-density lipoprotein (HDL) cholesterol and hypertriglyceridemia and raised oxidative stress [30, 31]. Diabetes also raises the risk of heart disease two- to fourfold. Therefore, uncontrolled hyperlipidemia leads to premature cardiovascular diseases (CVDs). CVD is the most common complication in diabetes, which is a common reason for premature mortality in diabetic patients. As a result, to reduce the risk of CVD, many studies potentially recommended control of dyslipidemia and hyperglycemia [1, 32–34].

In addition to dyslipidemia, hyperglycemia is known as a major risk factor for diabetic complications. Protein glycation is involved in the progress of complications such as retinopathy, neuropathy, nephropathy, dermopathy, and atherosclerotic lesions [1, 33, 35–37]. In the chronic state, excess glucose binds to free amino groups in tissue or blood proteins and body fluid and disturbs their functions [38–40]. This nonenzymatic reaction leads to formation of advanced glycosylation end products (AGEs). Glycation reaction leads to alteration in the structure and function of biomolecules particularly proteins. AGE formation is known as a key element in diabetes complications [41–46].

3.2. Free Radicals in Diabetes

In diabetic patients, reactive substances such as hydroxyl radicals (•OH), hydrogen peroxide (H₂O₂), lipid peroxyl radicals (LOO•), superoxide anion (), and peroxyl radicals (ROO•) are mainly generated during the developing stage of diabetes. The reaction of these reactive species with polyunsaturated fatty acids (PUFAs) causes lipid peroxidation which is consequently implicated in early diabetes complications, especially premature cardiovascular disease [47, 48].

Enzymatic antioxidant mechanisms play an important role in the elimination of free radicals. For instance, superoxide dismutase (SOD) is known as one of the main endogenous enzymes that removes and produces H₂O₂, which is then processed to water by the activity of catalase (CAT) and glutathione peroxidase (GPx). Hence, SOD can work as the chief protector against and it inhibits production of free radicals. CAT is an important enzyme involved in detoxification of hydrogen peroxide to water and oxygen. On the other hand, glutathione S-transferase (GST) and glutathione peroxidase (GPx) are other chief antioxidant enzymes [47, 49, 50]. GPx decreases free radical damage by preventing the production of extremely cytotoxic species, for instance, lipid peroxides and other organic hydroperoxides. GST is therefore believed to preserve the balance of cellular redox conditions [47, 49]. Lipid peroxidation naturally occurs on a small level in the body and plays a key role in diabetes and cardiovascular diseases pathogenesis. The reactive oxygen species such as hydroxyl radical and hydrogen peroxide attacks polyunsaturated fatty acids and causes lipid peroxidation. Iron ion and hydrogen peroxide in a known process, called Fenton reaction, lead to formation of hydroxyl radical which is a potent oxidative agent [15]. Oral administration of many herbal plants leads to a marked rise in the activities of SOD, CAT, GSH, GST, and GPx in diabetes [51, 52].

3.3. Diabetes Treatment

There are different ways for treatment and control of diabetes, including administration of insulin or hypoglycemic drugs, dietary control, and exercise [53, 54]. Furthermore, chemical drugs generally have low efficacy over time, are too expensive, and show severe side effects such that some patients cannot tolerate prolonged treatment or taking the high dosages of these drugs. In contrast, herbal medicines are regarded as potential sources for medication due to their useful effects, negligible side effects in clinical trials, and low cost [53–59].

3.4. Safety and Side Effects of Chemical Diabetic Medicines

People use different medicines such as sulfonylureas (glimepiride, glipizide, and glyburide), biguanides (metformin), thiazolidinediones (pioglitazone), alpha-glucosidase inhibitors (acarbose), meglitinides (nateglinide), and dipeptidyl peptidase 4 inhibitors (Januvia, Onglyza) for control and treatment of hyperglycemia. However, side effects can be seen in all diabetes drugs’ usage. More than 10 to 20 percent of diabetic patients are known to eventually stop taking their medications because of the side effects. Some of the diabetes medicines can also cause hypoglycemia which is a harmful and potentially lethal side effect. Additional side effects of several antidiabetic drugs are weight gain, increased risk for fractures especially in women, and gastrointestinal disorders such as abdominal pain, gassiness, vomiting, nausea, diarrhea, and bloating. Edema and increased level of low-density lipoprotein cholesterol (LDL-C) were also reported by many patients. Uncommon side effects include congestive heart failure, allergic reactions, and anemia, which can be induced by chemical diabetic medicines [30, 31].

3.5. Role of Herbal Medicine in the Treatment of Diabetes Mellitus

Nowadays, many physicians prescribe insulin, thiazolidinediones, sulphonylureas, α-glucosidase inhibitors, and so forth, for treatment and control of diabetic complications [75]. Nevertheless, since adverse effects of these medicines are arguable, there is a need for novel agents in diabetes treatment. In this respect, some herbal medicines due to their lower side effects, low costs, useful properties such as antihyperglycemic, antihyperlipidemic, and antioxidant effects, and especially their natural origin have been proposed for potential management of diabetes [76, 77]. However, because of unknown mechanisms, only a small number of plants have been used for the management of diabetic complications [78]. Herbal plants contain many chemical components such as flavonoids (30%), terpenoids (17%), saponins (9%), polyphenols (6%), alkaloids (5%), tannins (4%), polysaccharides (3%), and miscellaneous compounds (17%), which are known to have remedial properties [78]. Interestingly, the World Health Organization (WHO) reported that about 80% of the world’s people presently use herbal plants for treatment of different diseases [79]. Although many plants have been suggested for treatment of diabetes due to their antidiabetic properties, in this review, we will attempt to open a new window toward application of AG and its constituents in the management of type 2 diabetes.

3.6. Botanical Profile and Taxonomy of AG

The generic name of “Anethum” comes from the Greek word “anethon” and the colloquial name of dill is derived from the Old Norse word “dilla” that possibly means “to soothe.” AG is the only species of the genus Anethum, still classified by several botanists related to Peucedanum genus as Peucedanum graveolens (L.) [80]. AG is an annual vertical plant with 50–150 cm stem belonging to the Apiaceae family. The fruits of AG are brown, flat, tiny, and oval in shape (Figure 1). This plant is cultivated in Mediterranean countries, in Asia, and in Europe. AG contains 36% carbohydrates, 15.68% proteins, 14.80% fiber, 9.8% ash, and 8.39% moisture as well as essential oils, fatty oil, minerals, and vitamins [80].

Figure 1: Plant and seed of AG.

3.7. Traditional Uses of AG

AG is used in the traditional herbal medicine for the management and prevention of digestive disease, breath problem, motivation of lactation, and also reduction of cholesterol and glucose. Currently, many studies have established these properties; also, AG is recently known as anticancer, antimicrobial, antigastric irritation, anti-inflammatory, and antioxidant agent. In this respect, dill is produced as a hypolipidemic drug (Anethum tablet) in Iran which consists of Anethum graveolens (68%), Cichorium intybus (5%), Fumaria parviflora (5%), and lime (Citrus aurantifolia) (4%) [81].

3.8. Hypolipidemic and Hypoglycemic Properties of AG

Administration of different extractions of AG seed and leaf, as well as its essential oil, in diabetic models significantly reduced triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), and glucose levels, whereas it increased HDL-C level [80]. On the other hand, many studies reported that AG has hypoglycemic and antioxidant activity [80]. The antioxidant activity of AG is due to its phenolic proanthocyanidins and flavonoids constituents [24]. It has also been shown that the extract from AG flowers had more antioxidant activity than either its seed or leaf extract [80]. Duration of treatment in different experiments was variable; for example, Koppula and Choi [17] used only single dose for one hour, while the treatment period in Mansouri et al.’s [11] study was 12 weeks. However, almost all of the experiments show that one month is an appropriate time for survey of antidiabetic properties of dill.

To survey the effects of AG on dyslipidemia, different animals were used. The rabbit is known as an animal model that has been commonly used for the study of hypercholesterolemia. Only few studies have been done on rabbits, whereas rats are an optional model for diabetes studies [7]. Therefore, as mentioned in Table 1, most of the studies used diabetic rats.

Table 1: Antidiabetic effects of AG in different studies.

Reference
Preparation
Study model and duration
Pharmacological properties

[5]
Alkaloid extracted from AG
Hypercholesterolemic rabbits, 4 weeks
(i) Hypolipidemic effect

[6]
Ethanolic extract of AG seed
Alloxan induced diabetic mice, 15 days
(i) Hypoglycemic effects

[7]
Hydroalcoholic extract of AG
Hypercholesterolemic rabbits, 3 days
(i) Significant reduced glucose levels, LDL-C, TC, AST, ALT, and fibrinogen
(ii) The change in ApoB, factor VII, nitrite, and nitrate was not significant

[8]
Hydroalcoholic extract of AG
Hypercholesterolemic rabbits, 3 days
(i) Significantly declined TC, LDL-C, AST, ALT, and fibrinogen

[9]
Hexane extract of AG seed
High-fat-diet-induced hyperlipidemia and diabetic rat, 4 weeks
(i) Normalized blood lipid and glucose
(ii) Increased blood adiponectin levels
(iii) Significantly motivated FA oxidation by induced expression of FA oxidation-related genes (especially with activation of PPAR alpha) and also inhibited TG accumulation

[10]
Methanolic extract of AG
In vitro
(i) Antioxidant activity

[11]
Hydroalcoholic extract of AG
Patient with metabolic syndrome, 12 weeks
(i) Significantly reduced TG

[12]
Combined carnitine and hydroalcoholic extract of AG
Rat, 21 days
(i) AG does not improve serum lipids profiles

[13]
AG along with aerobic training
Type 2 diabetic patients, 4 weeks
(i) Hypoglycemic effects
(ii) Hypolipidemic effect

[14]
AG leaves powder
Hyperlipidemic patients, 4 weeks
(i) Hypolipidemic effect

[15]
Ethanolic extract of AG
Hepatotoxicity induced by carbon tetrachloride in albino rats, 21 days
(i) Antioxidant and hepatoprotective activity

[16]
Ethanolic extract of AG
In vitro
(i) Antioxidant and antiradical and antityrosinase activity
(ii) Inhibited lipid peroxidation

[17]
Aqueous extract of AG
Normal and scopolamine-induced amnestic rats, single dose
(i) Significant antistress and antioxidant memory enhancing and activity

[18]
AG tablet
STZ-induced diabetic mice, 21 days
(i) Significantly declined body weight, TG, and LDL-C and increased HDL
(ii) The change of blood glucose was not significant

[19]
Ethanolic extract and oil of AG
In vitro
(i) Antioxidant activity (ethanolic extract had higher activity than essential oil)

[20]
AG powder
Hyperlipidemic rats, 30 days
(i) Significant antioxidant and radical scavenging activity
(ii) Hypolipidemic effect

[21]
AG powder and essential oil
Hypercholesterolemic rat, 2 weeks
(i) Hypolipidemic effect

[22]
Hydroalcoholic extract of AG
Type 1 diabetic rats, 10 days
(i) Normalized blood lipids
(ii) Hypoglycemic effects (similar to glybenclamide)

[23]
Hydroalcoholic extract of AG
Corticosteroid induced diabetic rats, 15 days
(i) Significantly declined both plasma glucose and insulin levels
(ii) Antioxidant activity

[24]
Ethanolic extract of AG
Hyperlipidemic rats, 30 days
(i) Probably inhibited activity of HMG-CoA reductase
(ii) Hypolipidemic effect

[25]
Hydroalcoholic extract of AG seed extract
Rat, 6–168 hrs
(i) Antioxidant and antiradical activity
(ii) Significantly reduced liver enzymes

[26]
Anethum tablet twice daily (650 mg)
Hyperlipidemic patients, 6 weeks
(i) Normalized blood lipids

[27]
Anethum tablet twice daily (650 mg)
Hyperlipidemic patients, one month
(i) Hypolipidemic effect

[28]
Hydroalcoholic extract of AG
Alloxan induced diabetic mice, 48 h
(i) Hypolipidemic effect
(ii) Hypoglycemic effects

[29]
AG tablet
Hyperlipidemic patients, 1 month
(i) Hypolipidemic effect

Some primary mechanisms have been proposed for hypolipidemic effects of AG. Inhibition of intestinal cholesterol absorption, binding to bile acids in the intestine, an increase in fecal excretion, and increasing production of bile acids might be the main mechanisms by which AG exerts its antidiabetic functions [80]. Yazdanparast et al. [24, 82] proposed that some components of AG such as carvone, limonene, or α-phellandrene are responsible for the hypolipidemic properties of AG, likely through reducing acyl CoA carboxylase or 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the key enzymes in fatty acid and cholesterol metabolism. Other studies have suggested that AG components might rise liver LDL receptors, decrease fatty acid synthesis, and impact lipoprotein homeostasis mainly through improvement in lipoprotein metabolism [24]. Furthermore, some studies suggest that AG may improve the lipid profile by its antioxidant properties [10]. We have also observed that administration of 100 and 200 mg/kg of AG tablet and hydroalcoholic extract of AG in hypercholesterolemic hamsters resulted in significantly reduced HMG-CoA reductase activity and mRNA levels [83]. For the first time, we also showed that AG normalized the lipid profile by decreasing HMG-CoA reductase in the hypercholesterolemic hamsters and type 2 diabetic rats [83]. We have also shown that AG increased LDL receptor level in the liver resulting in stimulation of cholesterol clearance from the bloodstream (unpublished data). The results of Abbasi Oshaghi et al.’s [84] study showed that AG significantly increased cholesterol-7-alpha hydroxylase activity, the rate-limiting enzyme in bile acids biosynthesis [10]. Some studies have also reported that rutin and quercetin (components of dill) may decrease serum cholesterol and LDL-C levels and decrease liver cholesterol level. Other studies have also reported that quercetin reduces HMG-CoA reductase activity [24]. Histopathological experiments of Abbasi Oshaghi et al. [84] showed that treatment of diabetic rats with different extracts of AG normalized lipid deposits in the liver, pancreas, and heart. HPLC analysis showed that AG has high amounts of quercetin which may be responsible for the suppression of HMG-CoA reductase activity [10]. Numerous studies that have previously shown the antidiabetic effects of AG are listed in Table 1. Chemical compounds of AG extracts especially flavonoids, terpenoids, alkaloids, tannins, and phytosterols are probably responsible for its hypoglycemic effects [61]. We found that different extracts of AG reduce AGEs formation [85, 86]. Our study also showed that AG at the dose of 300 mg/kg had potential antioxidant and hypolipidemic effects [86]. Madani et al. [28] reported significant decline in fasting blood glucose level with 300 mg/kg hydroalcoholic extract of Anethum graveolens. Doses of AG up to 2 g/kg in a short period of time did not cause any death in animal models. Also, the AG doses up to 1000 mg/kg did not cause any toxic effect in short time experiments [87]. However, 50 mg/kg/day is the minimum and 1 g/kg/day is the maximum tolerated dose in a 45-day period [87]. Although different doses of AG were used in animal models, Ahmadi Mahmoudabadi [22] reported that the effective dose for metabolic properties is 300 mg/kg in animal models. Different studies showed that both high and low doses of AG have hypoglycemic and hypolipidemic effects. The doses less than 50 mg/kg could be known without adverse effect in rats and mice [87]. However, Piri et al. [18] demonstrated that 3-week administration of Anethum extract at the doses of 50, 100, and 200 mg/kg normalized blood lipid, and the change in blood glucose was not significant. The safe and effective dose in human studies is reported as 650 mg/kg [26]. In an in vitro study, Abbasi Oshaghi et al. [86] found that different extracts of AG at the concentrations of 0.032, 0.065, 0.125, 0.25, 0.5, and 1 mg/ml reduced AGEs formation; fructosamine level and carbonyl groups, also, raised thiol groups in type 2 diabetic animals. The components of AG are responsible for its antiglycation properties. Oxidation of carbonyl and thiol groups on blood proteins significantly reduces by Anethum in a dose dependent manner [28].

According to the study conducted by Adisakwattana et al. [88], polyphenolic compounds in plant extract may play a major role in the inhibition of AGEs formation. AGEs are recognized to contribute to the production of oxidative stress and inflammation, which are related to the diabetes complications. It has been reported that administration of AGE-rich diets in an animal model is associated with rising of blood and tissue AGEs and the conditions like atherosclerosis [89]. Mobasseri et al. [90] showed that administration of AG powder in type 2 diabetic patients reduced fasting blood glucose and normalized insulin resistance and lipid profiles. As mentioned above, AG is rich in antioxidant compounds; therefore, antioxidant and flavonoid components of AG probably are able to repair damaged β-cells and insulin secretion. It has been shown that AG significantly increases total antioxidants in the pancreas and also regenerates histopathological changes [84]. Therefore, AG with antioxidant activity likely increases insulin synthesis. Some researchers such as Madani et al. [28] and Mishra [6] reported that AG reduced blood glucose via the increase of insulin secretion. Takahashi et al. [91] have shown that AG extract normalized lipid profile in diabetic obese mice by activating peroxisome proliferator-activated receptor-α (PPAR-α) and increasing fatty acid oxidation-related genes expression.

Our colorimetric and HPLC analysis also showed that dill had a high amount of quercetin, phenol, flavonoid, tannin, saponin, and alkaloid [84]. All of these agents have hypoglycemic and hypolipidemic properties. Therefore, we can conclude that components of dill are responsible for its metabolic effects. Mishra [6] reported that aqueous extract of AG has a high amount of carvone, which is accountable for its antidiabetic activity. Carvone is able to cause decline in plasma glycoprotein components and motivate insulin secretion. The ethanolic extract of AG which is prepared in India showed very low antidiabetic properties [6]. On the other hand, Mudassir et al. [92] reported that the prepared ethanolic extract of AG in Pakistan significantly reduced blood glucose (34% reduction). They declared that hypoglycemic effects of AG might be due to the inhibition of intestinal glucose absorption [92].

In our laboratory, we have previously shown that AG has potential antioxidant activity [85]. Our results are in agreement with the results of a previous study by Bahramikia and Yazdanparast [20], indicating DPPH radical scavenging activity of AG. In our study, 1 mg/ml of AG water extract showed 96.04% scavenging of H₂O₂, whereas only 27.26% radical scavenging activity was reported for AG ethanolic extract [86]. AG also showed Fe²⁺ ion chelation which is known as a defense mechanism against oxidative damage by declining free radical production via Fenton reaction. In this reaction, iron(II) is oxidized by H₂O₂ to create potential free radicals such as hydroxyl radical. Nitric oxide scavenging activity has also been proposed for AG [20]. The results of a study by Bahramikia and Yazdanparast [20] showed that crude extract of AG exhibited a moderate NO scavenging activity. In line with this observation, we showed a nitric oxide scavenging activity of AG similar to the known radical scavengers, ascorbic acid and butylated hydroxytoluene (BHT) [86]. Interestingly, we showed that NO scavenging activity of AG is comparable with the activity of ascorbic acid and/or BHT. We showed that a 1 mg/ml solution of dill water extract has 90.41% NO scavenging activity which was much greater than that observed (78.49%) for ethanolic extract of AG by Orhan et al. [93]. We have also detected a greater antioxidant activity for AG water extract compared with methanolic extracts [85]. Interestingly, the antiradical and antioxidant properties of AG in all tests were similar to ascorbic acid and BHT [80]. The results of many studies established the notion that the particular parts of dill are often discriminated by significant diversity in their constituents’ chemical compounds. It has been reported that ethanolic extract of AG has very low antidiabetic properties when compared with the aqueous extract [6]. However, Mishra reported that ethanolic extract of AG has hypoglycemic effects [6]. Concordant with the hypoglycemic function of AG ethanolic extract, other studies have reported that this extract significantly reduces blood lipids [24, 82]. Interestingly, we showed that different extracts of AG significantly reduced glucose level, but the reduction by water or hydroalcoholic extract was more as compared with the methanolic extract [86]. Furthermore, with review of the literature, we can find that different preparations such as hexane, ethanolic, water, and hydroalcoholic extracts of seed and leaf have been used in different studies (Table 1). However, the hydroalcoholic extract showed stronger antidiabetic effects compared with other extracts.

3.9. Chemical Composition

There is some diversity in the dill composition in different countries; for example, American dill oil has a high amount of alpha-phellandrene, while carvone and limonene are the main constituents of Asian and European dill [94]. In addition to essential oils especially carvone, limonene, and alpha-phellandrene, dill also contains fatty oil, proteins, carbohydrates, moisture, fiber, ash, vitamins (A and niacin), and mineral elements (calcium, potassium, magnesium, phosphorus, and sodium). This plant is known as a rich source of flavonoids, phenolic compounds, saponins, cardiac glycosides, and terpenes [80].

Jana and Shekhawat [80] reported that there are several volatile components of AG seeds and herb. For instance, carvone is the main odorant of AG seed and limonene, α-phellandrene, myristicin, and dill ether are the most vital odorants of AG herb. Larijani et al. [63] also reported that seeds and leaves of AG have different components and consequently have different therapeutic effects. Different parameters such as cultivating area, genotype, and environmental factors have huge effects on the composition of AG extracts [80]. Furthermore, Reichert et al. [95] reported that the different parts of AG have different compounds and these compounds may change depending on the stage of plant growth. For example, Sefidkon [96] reported that α-phellandrene and limonene are the major constituents of dill oil, while Singh [64] showed that carvone, dill apiole, limonene, trans- and cis-dihydrocarvone, and linalool are the main constituents. Consequently, the different components which are reported by the different studies also depend on the different plant growth stage, cultivating area, and the particular part of the plant that is used. Different compounds of AG have been described in the different published reports which are listed in Table 2.

Table 2: Components of AG in different studies.

References
Preparation
Components

[60]
Essential oil
Carvone, α-pinene, α-phellandrene, myrcene, dillapiole, anethole, p-cymene, limonene, dill ether, trans-dihydrocarvone, cis-dihydrocarvone, camphor

[61]
Dill seed oil
Carvone, limonene, gamma-terpinene, m-cymene, apiol, myristicin, trans-dihydrocarvone

[62]
Dill seed oil
Glycosides, reducing sugar, tannins, saponins, flavonoids, steroids, flavonosides, terpenoids

[63]
Dill seed oil
α-Phellandrene, sabinene bicycle, trans-caryophyllene, beta-santalene, eugenol, pentadecane, dill apiole, hexadecanol, methyl undecanoate, limonene, eudesmol, n-octane, mefranal, D-carvone, cyclohexasiloxane

[64]
Essential oil
α-Thujene, cyclohexane, β-myrcene, β-phellandrene, grandisol, thujyl alcohol, carvone, bis-1,2-benzenedicarboxylic acid, limonene

[65]
Essential oil
α-Pinene, β-pinene, α-thujene, β-phellandrene, α-cadinol, sabinene, (Z)-anethole, α-phellandrene, limonene, myristicin, γ-terpinene, β-myrcene, dimethyl phencone, phencone, linalool, dill ether, p-cymene, (Z)-dihydrocarvone, (E)-dihydrocarvone, (E)-carveol, carvone, apiole, phthalide isomer, D-germacrene, epi-bicyclosesquiphellandrene

[66]
Essential oil
α-Pinene, α-phellandrene, α-thujene, β-phellandrene, β-myrcene, carvone, dill ether, n-eicosane, limonene, n-eicosane, terpinolene, trans-dihydrocarvone, sabinol, apiole

[67]
Essential oil
Limonene, dill ether, α-thujene, sabinene, β-myrcene, α-pinene, p-cymene, α-phellandrene, cis-dihydrocarvone, carvone, cadinol, trans-dihydrocarvone, α-copaene, γ-muurolene, neophytadiene, n-nonadecane, n-docosane, n-heneicosane, n-tricosane, n-tetracosane, n-eicosane, n-pentacosane, n-heptacosane, n-hexacosane

[68]
Essential oil
Limonene, linalool, D-carvone, carvacrol, sabinene, dihydrocarvone, β-myrcene, ρ-cymene, γ-terpinene, E-limonene oxide, estragole, α-pinene, terpineol, cumin aldehyde, β-caryophyllene, D-germacrene, α-phellandrene, thymol, dill apiole, myristicin

[69]
Dill flower extract
Gentisic acid, kaempferol, gallic acid, catechin, chlorogenic acid, luteolin, epicatechin, p-coumaric acid, sinapic acid, benzoic acid, p-anisic acid, myricetin, quercetin, caffeic acid, total phenolic acid, apigenin, proanthocyanidins, total flavonoid

[70]
Dill seed oil
cis-Dihydrocarvone, farnesene, m-carveol, dihydrocarvone, D-carvone, myristicin, cis-dihydrocarveol, 3,5-dimethylcyclohexen-1-one, limonene, diplaniol, 1,2-diethoxyethane, α-phellandrene, β-myrcene, limonene, ethylacetate, sabinene, α-humulene, carvone, cis-carvone

[21]
Dill weed oil
Dill ether, limonene, α-phellandrene, α-pinene

[71]
Dill oil and acetone extract
α-Pinene, α-ylangene, α-thujene, foeniculin, sabinene, myrcene, p-cymene, sylvestrene, isocaryophyllene, terpinolene, linalool, trans-carveol, camphor, dill ether, cis-dihydrocarvone, trans-dihydrocarvone, undecane, isodihydrocarveol, geranyl acetate, carvone, limonene, α-humulene, D-germacrene, β-caryophyllene, β-selinene, trans-guaiene, α-cadinene, β-bisabolene, trans-isocroweacin, dill apiole, apiole, elemicin, trans-anethole, eugenol, p-anisaldehyde, lauric aldehyde, trans-bergamotene, nonadecanone, myristicin, trans-muurolol, heptadecane, neophytadiene, palmitic acid, linoleic acid, γ-terpinene

[72]
Essential oil
α-Thujene, α-phellandrene, camphene, sabinene, α-pinene, myrcene, p-cymene, limonene, β-phellandrene, (Z)-β-ocimene, (E)-β-ocimene, terpinolene, α-p-dimethyl styrene, carvone, bornyl acetate, D-germacrene, β-bisabolene, myristicin, T-cadinol, phthalide isomer, farnesol, apiole, n-octadecane, n-heptadecane, n-nonadecane

[73]
Essential oil
Glycosides, saponins, tannins, terpenoids, steroids, flavonoids, phlobatannin, cardiac glycoside, anthraquinone

[74]
Fruit essential oil
Carvacrol, D-carvone, cis-carveol, trans-carveol, cis-dihydrocarvone, trans-dihydrocarvone, limonene, terpinene-4-ol, d-dihydrocarveol, l-dihydrocarveol, a- and g-terpinene, thymol, a-phellandrene, b-terpineol, p-cymene

3.10. Adverse Effects

However, it has been shown that AG administration is safe, and it may rarely lead to allergic reactions, vomiting, diarrhea, oral pruritus, urticaria tongue, and throat swelling [97]; furthermore, it is not suggested in pregnancy [97]. Mirhosseini et al. [98] reported that AG did not have any side effects, as compared with gemfibrozil, in treated patients. Other clinical trial studies did not report the side effect of AG [11, 13, 26, 27].

4. Conclusion

Herbal medicines have multiple key components such as flavonoids, terpenoids, saponins, polyphenols, tannins, alkaloids, and polysaccharides that have their individual remedial properties. The use of herbal medicines is not a novel matter. Herbal medicines especially AG have a lot of useful properties including antihyperlipidemic, antihypercholesterolemic, antidiabetic, anticancer, antioxidant, antistress, antisecretory, cardioprotective, antispasmodic, and diuretic effects. Moreover, epidemiologic experiments reported a converse relationship between AG consumption and risk of diabetes and CVD progression. Recent literature strongly supports the suggestion that consumption of AG has a significant antidiabetic effect in both humans and animals. According to the reported antidiabetic effects of dill, it can be suggested for the management of diabetic patients. However, the diverse preparations, dose of AG, period of AG consumption, and interaction with other drugs must be normalized. More studies are required to recognize the specific constituents of AG that are accountable for most of its valuable properties. Although all components of AG have antioxidant, hypoglycemic, and hypolipidemic effects, these components are at low levels in dill and possibly have synergic effects. Moreover, the findings suggest that activation of LDL-R, PPAR-alpha, and other FA oxidation-related genes and also inhibition of HMG-CoA reductase contribute to the hypolipidemic effects of AG.

Competing Interests

The authors have no competing interests to disclose.

References

M. Ståhlman, B. Fagerberg, M. Adiels et al., “Dyslipidemia, but not hyperglycemia and insulin resistance, is associated with marked alterations in the HDL lipidome in type 2 diabetic subjects in the DIWA cohort: impact on small HDL particles,” Biochimica et Biophysica Acta (BBA)—Molecular and Cell Biology of Lipids, vol. 1831, no. 11, pp. 1609–1617, 2013.

M. Rabkin, Z. Melaku, K. Bruce et al., “Strengthening health systems for chronic care: leveraging HIV programs to support diabetes services in Ethiopia and Swaziland,” Journal of Tropical Medicine, vol. 2012, Article ID 137460, 6 pages, 2012.

D. R. Whiting, L. Guariguata, C. Weil, and J. Shaw, “IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030,” Diabetes Research and Clinical Practice, vol. 94, no. 3, pp. 311–321, 2011.

S. Wild, G. Roglic, A. Green, R. Sicree, and H. King, “Global prevalence of diabetes: estimates for the year 2000 and projections for 2030,” Diabetes Care, vol. 27, no. 5, pp. 1047–1053, 2004.

A. J. Al-Fartosy, S. A. Zearah, and N. A. Alwan, “Total antioxidant capacity and antihyperlipidemic activity of alkaloid extract from aerial part of Anethum graveolens L. plant,” European Scientific Journal, vol. 9, no. 33, pp. 413–423, 2013.

N. Mishra, “Haematological and hypoglycemic potential Anethum graveolens seeds extract in normal and diabetic Swiss albino mice,” Veterinary World, vol. 6, no. 8, pp. 502–507, 2013.

M. Setorki, M. Rafieian-Kopaei, A. Merikhi et al., “Suppressive impact of anethum graveolens consumption on biochemical risk factors of atherosclerosis in hypercholesterolemic rabbits,” International Journal of Preventive Medicine, vol. 4, no. 8, pp. 889–895, 2013.

M. Setorkil, N. Shahinfard, R. Ansari, Z. Foronzandeh, S. Asgharzadeh, and M. Rafieian-Kopaei, “Comparison between the effects of hydroalcoholic extract of dill and statins on lipid profile,” Journal of Kerman University of Medical Sciences, vol. 20, no. 2, pp. 158–168, 2013.

N. Takahashi, L. Yao, M. Kim et al., “Dill seed extract improves abnormalities in lipid metabolism through peroxisome proliferator-activated receptor-α (PPAR-α) activation in diabetic obese mice,” Molecular Nutrition & Food Research, vol. 57, no. 7, pp. 1295–1299, 2013.

H. Edziri, S. Ammar, L. Souad et al., “In vitro evaluation of antimicrobial and antioxidant activities of some Tunisian vegetables,” South African Journal of Botany, vol. 78, pp. 252–256, 2012.

M. Mansouri, N. Nayebi, A. Keshtkar, S. Hasani-Ranjbar, E. Taheri, and B. Larijani, “The effect of 12 weeks Anethum graveolens (dill) on metabolic markers in patients with metabolic syndrome; A randomized double blind controlled trial,” DARU Journal of Pharmaceutical Sciences, vol. 20, no. 1, article 47, 2012.

A. K. Rezapour and H. H. Maleki, “The effect of combined carnitine and dill extract complementation on serum lipids of male fat rats,” International Journal of Agronomy and Plant Production, vol. 3, no. 12, pp. 638–641, 2012.

A. Rashid Lamir and S. A. A. Hashemi Javaheri, “The effect of 4-weeks aerobic training according with the usage of Anethum Graveolens on blood sugar and lipoproteins profile of diabetic women,” Annals of Biological Research, vol. 3, no. 9, pp. 4313–4319, 2012.

A. S. Sahib, I. H. Mohammad, and A. AlGareeb, “Effects of Anethum graveolens leave powder on lipid profile in hyperlipidemic patients,” Spatula DD, vol. 2, no. 2, pp. 153–158, 2012.

R. Tamilarasi, D. Sivanesan, and P. Kanimozhi, “Hepatoprotective and antioxidant efficacy of Anethum graveolens Linn in carbon tetrachloride induced hepatotoxicity in Albino rats,” Journal of Chemical and Pharmaceutical Research, vol. 4, no. 4, pp. 1885–1888, 2012.

M. Dadashpour, I. Rasooli, F. Sefidkon, M. B. Rezaei, and S. Danish Alipour Astaneh, “Lipid peroxidation inhibition, superoxide anion and nitric oxide radical scavenging properties of Thymus daenensis and Anethum graveolens essential oils,” Journal of Medicinal Plants, vol. 1, no. 37, pp. 109–120, 2011.

S. Koppula and D. K. Choi, “Anethum Graveolens linn (Umbelliferae) extract attenuates stress-induced urinary biochemical changes and improves cognition in scopolamineinduced amnesic rats,” Tropical Journal of Pharmaceutical Research, vol. 10, no. 1, pp. 47–54, 2011.

M. Piri, M. Shahin, and S. Oryan, “The effects of Anethum on plasma lipid and lipoprotein in normal and diabetic rats fed high fat diets,” Journal of Shahrekord University of Medical Sciences, vol. 11, no. 4, pp. 15–25, 2010.

A. Kamkar, “The study of antioxidant activity of essential oil and extract of Iranian Anethum graveloens,” The Horizon of Medical Sciences, vol. 15, no. 2, pp. 11–16, 2009.

S. Bahramikia and R. Yazdanparast, “Efficacy of different fractions of Anethum graveolens leaves on serum lipoproteins and serum and liver oxidative status in experimentally induced hypercholesterolaemic rat models,” The American Journal of Chinese Medicine, vol. 37, no. 4, pp. 685–699, 2009.

V. Hajhashemi and N. Abbasi, “Hypolipidemic activity of Anethum graveolens in rats,” Phytotherapy Research, vol. 22, no. 3, pp. 372–375, 2008.

N. Ahmadi Mahmoudabadi, “The effects of hydroalcoholic extracts of dill (Anethum graveolens L.) and artichoke (Cynara scolymus L.) against type 1 diabetes mellitus,” Iranian Journal of Medicinal And Aromatic Plants, vol. 24, no. 3, pp. 333–341, 2008.

S. Panda, “The effect of Anethum graveolens L. (dill) on corticosteroid induced diabetes mellitus: involvement of thyroid hormones,” Phytotherapy Research, vol. 22, no. 12, pp. 1695–1697, 2008.

R. Yazdanparast and S. Bahramikia, “Evaluation of the effect of Anethum graveolens L. crude extracts on serum lipids and lipoproteins profiles in hypercholesterolaemic rats,” DARU Journal of Pharmaceutical Sciences, vol. 16, no. 2, pp. 88–94, 2008.

M. Taher and A. G. R. Karmiyan, “Effects of volatile oil extracts of Anethum graveolens L. and Apium graveolens L. seeds on activity of liver enzymes in rat,” The Journal of Qazvin University of Medical Sciences, vol. 11, no. 2, pp. 8–12, 2007.

J. Kojuri, A. R. Vosoughi, and M. Akrami, “Effects of anethum graveolens and garlic on lipid profile in hyperlipidemic patients,” Lipids in Health and Disease, vol. 6, article 5, pp. 1476–1512, 2007.

T. Kazemi, M. Kashanian, and H. Akbari, “Effect of Dill pearl on serum lipids,” Arak Medical University Journal, vol. 8, no. 3, pp. 35–41, 2006.

H. Madani, N. Ahmady Mahmoodabady, and A. Vahdati, “Effects of hydroalchoholic extract of Anethum graveolens (Dill) on plasma glucose an lipid levels in diabetes induced rats,” Iranian Journal of Diabetes and Metabolism, vol. 5, no. 2, pp. 109–116, 2005.

K. Yazdanpanah, “Effects of dill juice on serum low density lipoprotein, triglyceride and high density lipoprotein in patients with hyperlipidemia,” Scientific Journal of Kurdistan University of Medical Sciences, vol. 5, no. 3, p. 1, 2001.

P. Barter, A. M. Gotto, J. C. LaRosa et al., “HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events,” The New England Journal of Medicine, vol. 357, no. 13, pp. 1301–1310, 2007.

J. van Olmen, F. Schellevis, W. Van Damme, G. Kegels, and F. Rasschaert, “Management of chronic diseases in sub-Saharan Africa: cross-fertilisation between HIV/AIDS and diabetes care,” Journal of Tropical Medicine, vol. 2012, Article ID 349312, 10 pages, 2012.

A. Mohammadi, M. R. Bazrafshani, and E. Abbasi Oshaghi, “Effect of garlic extract on some serum biochemical parameters and expression of npc1l1, abca1, abcg5 and abcg8 genes in the intestine of hypercholesterolemic mice,” Indian Journal of Biochemistry & Biophysics, vol. 50, no. 6, pp. 500–504, 2013.

J. Shahryari, M. Poormorteza, A. Noori Sorkhani et al., “The effect of concomitant ethanol and opium consumption on lipid profiles and atherosclerosis in golden syrian Hamster's aorta,” Addiction & Health, vol. 5, no. 3-4, p. 83, 2013.

A. Mohammadi, E. A. Oshaghi, A. N. Sorkhani, F. Oubari, R. H. Kia, and A. Rezaei, “Effect of opium on lipid profile and expression of liver X receptor alpha (LXRα) in normolipidemic mouse,” Food and Nutrition Sciences, vol. 3, no. 2, pp. 249–254, 2012.

C. Wekesa, G. Asiki, I. Kasamba et al., “Atherogenic risk assessment among persons living in rural uganda,” Journal of Tropical Medicine, vol. 2016, Article ID 7073894, 8 pages, 2016.

A. Mohammadi, F. Mirzaei, M. Jamshidi et al., “Influence of flaxseed on lipid profiles and expression of LXRα, in intestine of diabetic rat,” International Journal of Biology, vol. 5, no. 4, pp. 23–29, 2013.

A. Mohammadi, F. Mirzaei, M. N. Moradi et al., “Effect of flaxseed on serum lipid profile and expression of NPC1L1, ABCG5 and ABCG8 genes in the intestine of diabetic rat,” Avicenna Journal of Medical Biochemistry, vol. 1, no. 1, pp. 1–6, 2013.

M. T. Goodarzi, S. Ghahramany, and M. Hossien, “Glycation of human IgG induces structural alterations leading to changes in its interaction with anti-IgG,” Iranian Journal of Immunology, vol. 2, no. 1, pp. 36–42, 2005.

M. T. Goodarzi, S. Ghahramany, and M. H. Mirmomeni, “In vitro glycation of human IgG and its effect on interaction with anti-IgG,” Iranian Journal of Allergy, Asthma and Immunology, vol. 3, no. 4, pp. 181–188, 2004.

M. T. Goodarzi, M. Rezaei, H. Piry, and S. Amiry, “Effect of in vitro glycation of human placental collagen (Type IV) on platelet aggregation,” Pakistan Journal of Biological Sciences, vol. 8, no. 9, pp. 1203–1206, 2005.

M. T. Goodarzi, M. Rezaei, E. Moadel, S. Homayounfar, and M. R. Safari, “Changes in sialylation of low-density lipoprotein in coronary artery disease,” European Journal of Lipid Science and Technology, vol. 110, no. 4, pp. 302–306, 2008.

M. T. Goodarzi, A. A. Navidi, M. Rezaei, and H. Babahmadi-Rezaei, “Oxidative damage to DNA and lipids: correlation with protein glycation in patients with type 1 diabetes,” Journal of Clinical Laboratory Analysis, vol. 24, no. 2, pp. 72–76, 2010.

M. T. Goodarzi, H. Babaahmadi-Rezaei, M. Kadkhodaei-Eliaderani, and S. Haddadinezhad, “Relationship of serum adiponectin with blood lipids, HbA1c, and hs-CRP in type II diabetic postmenopausal women,” Journal of Clinical Laboratory Analysis, vol. 21, no. 3, pp. 197–200, 2007.

N. Ahmed, “Advanced glycation endproducts—role in pathology of diabetic complications,” Diabetes Research and Clinical Practice, vol. 67, no. 1, pp. 3–21, 2005.

K. Adeli, C. Taghibiglou, S. C. Van Iderstine, and G. F. Lewis, “Mechanisms of hepatic very low-density lipoprotein overproduction in insulin resistance,” Trends in Cardiovascular Medicine, vol. 11, no. 5, pp. 170–176, 2001.

I. Lubitz, J. Ricny, D. Atrakchi-Baranes et al., “High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model,” Aging Cell, vol. 15, no. 2, pp. 309–316, 2016.

A. C. Maritim, R. A. Sanders, and J. B. Watkins III, “Diabetes, oxidative stress, and antioxidants: a review,” Journal of Biochemical and Molecular Toxicology, vol. 17, no. 1, pp. 24–38, 2003.

A. Mohammadi, F. Mirzaei, M. Jamshidi et al., “The in vivo biochemical and oxidative changes by ethanol and opium consumption in syrian hamsters,” International Journal of Biology, vol. 5, no. 4, p. 14, 2013.

R. Rahimi, S. Nikfar, B. Larijani, and M. Abdollahi, “A review on the role of antioxidants in the management of diabetes and its complications,” Biomedicine & Pharmacotherapy, vol. 59, no. 7, pp. 365–373, 2005.

F. Mirzaeipour, N. Azdaki, G. A. Mohammadi, and E. Addasi, “The effects of opium addiction through different administration routes on inflammatory and coagulation factors,” Journal of Kerman University of Medical Sciences, vol. 20, no. 3, pp. 292–300, 2013.

M. Modak, P. Dixit, J. Londhe, S. Ghaskadbi, and T. P. A. Devasagayam, “Indian herbs and herbal drugs used for the treatment of diabetes,” Journal of Clinical Biochemistry and Nutrition, vol. 40, no. 3, pp. 163–173, 2007.

A. Mohammadi, P. Norouzian, M. Jamshidi et al., “Effect of garlic (Allium sativum) on lipid profiles, antioxidant activity and expression of scavenger receptor class B type I (SR-BI) in liver and intestine of hypercholesterolemic mice,” Journal of Advances in Chemistry, vol. 5, no. 3, pp. 784–791, 2013.

V. Somsak, S. Chachiyo, U. Jaihan, and S. Nakinchat, “Protective effect of aqueous crude extract of neem (Azadirachta indica) leaves on Plasmodium berghei-induced renal damage in mice,” Journal of Tropical Medicine, vol. 2015, Article ID 961205, 5 pages, 2015.

G. Alvarez-Uria, M. Midde, R. Pakam, P. S. Yalla, P. K. Naik, and R. Reddy, “Short-course induction treatment with intrathecal amphotericin B lipid emulsion for HIV infected patients with cryptococcal meningitis,” Journal of Tropical Medicine, vol. 2015, Article ID 864271, 6 pages, 2015.

P. Modi, “Diabetes beyond insulin: review of new drugs for treatment of diabetes mellitus,” Current Drug Discovery Technologies, vol. 4, no. 1, pp. 39–47, 2007.

J. P. Overington, B. Al-Lazikani, and A. L. Hopkins, “How many drug targets are there?” Nature Reviews Drug Discovery, vol. 5, no. 12, pp. 993–996, 2006.

S. Parvazi, S. Sadeghi, M. Azadi et al., “The effect of aqueous extract of cinnamon on the metabolome of Plasmodium falciparum using ¹HNMR spectroscopy,” Journal of Tropical Medicine, vol. 2016, Article ID 3174841, 5 pages, 2016.

A. Mohammadi, S. A. Vafaei, M. N. Moradi, M. Ahmadi, M. Pourjafar, and E. Abbasi Oshaghi, “Combination of ezetimibe and garlic reduces serum lipids and intestinal Niemann-Pick C1-like 1 expression more effectively in hypercholesterolemic mice,” Avicenna Journal of Medical Biochemistry, vol. 3, no. 1, pp. 1–5, 2015.

M. Abbas, N. Mohammadi, N. Nader et al., “Influence of flaxseed on some biochemical factors, antioxidant activity and expression of ABCG5 and ABCG8 genes in the liver of diabetic rat,” British Journal of Medicine and Medical Research, vol. 4, no. 18, pp. 3571–3580, 2014.

F. S. Sharopov, W. Michael, I. S. Gulmurodov, and J. Salomiddin, “Composition and bioactivity of the essential oil of Anethum graveolens L. from Tajikistan,” International Journal of Medicinal and Aromatic Plants, vol. 3, no. 2, pp. 125–130, 2013.

R. A. Babri, I. Khokhar, Z. Mahmood, and S. Mahmud, “Chemical composition and insecticidal activity of the essential oil of Anethum graveolens L.,” Science International (Lahore), vol. 24, no. 4, pp. 453–455, 2012.

P. Dahiya and S. Purkayastha, “Phytochemical analysis and antibacterial efficacy of dill seed oil against multi-drug resistant clinical isolates,” Asian Journal of Pharmaceutical and Clinical Research, vol. 5, no. 2, pp. 62–64, 2012.

K. Larijani, M. J. Shakouri, N. Pishbin, S. Mansourbahmani, and A. A. Heidari, “The essential oils of Dill (Anethum graveblens L.) collected from Gilan, Iran,” Annals of Biological Research, vol. 3, no. 2, pp. 1010–1013, 2012.

S. Singh, “Chemical constituents of essential oil from Anethum sowa Kurz. seed,” Journal of Chemical and Pharmaceutical Research, vol. 4, no. 9, pp. 4156–4160, 2012.

R. Vokk, T. Lõugas, K. Mets, and M. Kravets, “Dill (Anethum graveolens L.) and parsley (Petroselinum crispum (Mill.) Fuss) from Estonia: seasonal differences in essential oil composition,” Agronomy Research, vol. 9, no. 2, pp. 515–520, 2011.

B. Andalibi, S. Zehtab Salmasi, K. Ghassemi Gholezani, and J. Saba, “Changes in essential oil yield and composition at different parts of dill (Anethum graveolens L.) under limited irrigation conditions,” Journal of Agricultural Science, vol. 21, no. 2, pp. 11–22, 2011.

V. Rãdulescu, M. L. Popescu, and D.-C. Ilieş, “Chemical composition of the volatile oil from different plant parts of Anethum graveolens L. (Umbelliferae) cultivated in Romania,” Farmacia, vol. 58, no. 5, pp. 594–600, 2010.

F. Oyoughi, M. Barzegar, M. Sahari, and H. N. Badi, “Effect of some of plant extracts on the growth of two Aspergillus species,” Iranian Journal of Medicinal Plants, vol. 2, pp. 1–13, 2009.

Y.-S. Shyu, J.-T. Lin, Y.-T. Chang, C.-J. Chiang, and D.-J. Yang, “Evaluation of antioxidant ability of ethanolic extract from dill (Anethum graveolens L.) flower,” Food Chemistry, vol. 115, no. 2, pp. 515–521, 2009.

A. Yili, H. A. Aisa, V. V. Maksimov, O. N. Veshkurova, and S. I. Salikhov, “Chemical composition and antimicrobial activity of essential oil from seeds of anethum graveolens growing in uzbekistan,” Chemistry of Natural Compounds, vol. 45, no. 2, pp. 280–281, 2009.

G. Singh, S. Maurya, M. P. De Lampasona, and C. Catalan, “Chemical constituents, antimicrobial investigations, and antioxidative potentials of Anethum graveolens L. essential oil and acetone extract—part 52,” Journal of Food Science, vol. 70, no. 4, pp. M208–M215, 2005.

A. Orav, T. Kailas, and A. Jegorova, “Bioactivities of l-carvone, d-carvone, and dihydrocarvone toward three stored product beetles,” Estonian Academy of Sciences, vol. 52, no. 4, 2003.

P. A. G. Santos, A. C. Figueiredo, P. M. L. Lourenço et al., “Hairy root cultures of Anethum graveolens (dill): establishment, growth, time-course study of their essential oil and its comparison with parent plant oils,” Biotechnology Letters, vol. 24, no. 12, pp. 1031–1036, 2002.

M. Miyazawa and H. Kameoka, “Constitution of the volatile oil from dill seed,” Japan Oil Chemists Society, vol. 23, p. 746, 1974.

H. Javad, H.-Z. Seyed-Mostafa, O. Farhad et al., “Hepatoprotective effects of hydroalcoholic extract of Allium hirtifolium (Persian shallot) in diabetic rats,” Journal of Basic and Clinical Physiology and Pharmacology, vol. 23, no. 2, pp. 83–87, 2012.

G. Y. Yeh, D. M. Eisenberg, T. J. Kaptchuk, and R. S. Phillips, “Systematic review of herbs and dietary supplements for glycemic control in diabetes,” Diabetes Care, vol. 26, no. 4, pp. 1277–1294, 2003.

M. O. Nafiu, T. A. Abdulsalam, and M. A. Akanji, “Phytochemical analysis and antimalarial activity aqueous extract of Lecaniodiscus cupanioides root,” Journal of Tropical Medicine, vol. 2013, Article ID 605393, 4 pages, 2013.

C. J. Bailey and C. Day, “Traditional plant medicines as treatments for diabetes,” Diabetes Care, vol. 12, no. 8, pp. 553–564, 1989.

F. O. A. Ajose, “Some Nigerian plants of dermatologic importance,” International Journal of Dermatology, vol. 46, supplement 1, pp. 48–55, 2007.

S. Jana and G. Shekhawat, “Anethum graveolens: an indian traditional medicinal herb and spice,” Pharmacognosy Reviews, vol. 4, no. 8, pp. 179–184, 2010.

E. A. Oshaghi, I. Khodadadi, H. Tavilani, and M. Goodarzi, “Effect of dill tablet (Anethum graveolens L) on antioxidant status and biochemical factors on carbon tetrachloride-induced liver damage on rat,” International Journal of Applied and Basic Medical Research, vol. 6, no. 2, pp. 111–114, 2016.

R. Yazdanparast and M. Alavi, “Antihyperlipidaemic and antihypercholesterolaemic effects of Anethum graveolens leaves after the removal of furocoumarins,” Cytobios, vol. 105, no. 410, pp. 185–191, 2000.

E. Abbasi Oshaghi, I. Khodadadi, M. Saidijam et al., “Lipid lowering effects of hydroalcoholic extract of Anethum graveolens L. and dill tablet in high cholesterol fed hamsters,” Cholesterol, vol. 2015, Article ID 958560, 7 pages, 2015.

E. Abbasi Oshaghi, S. Arash Noori, and R. Ali, “Effects of walnut on lipid profile as well as the expression of sterol-regulatory element binding protein-1c (SREBP-1c) and peroxisome proliferator activated receptors α (PPARα) in diabetic rat,” Food and Nutrition Sciences, vol. 3, no. 2, pp. 255–259, 2012.

E. Abbasi Oshaghi, I. Khdadadi, H. Tavilani, and M. T. Goodarzi, “Aqueous extract of Anethum Graveolens L. has potential antioxidant and antiglycation effects,” Iranian Journal of Medical Sciences, vol. 41, no. 4, pp. 328–333, 2016.

E. Abbasi Oshaghi, H. Tavilani, I. Khodadadi, and M. T. Goodarzi, “Dill tablet: a potential antioxidant and anti-diabetic medicine,” Asian Pacific Journal of Tropical Biomedicine, vol. 5, no. 9, pp. 720–727, 2015.

B. S. Arbabi, E. Taheri, H. Baher, and P. Ziarati, “Safety evaluation of oral anethum graveolens L total hydroalcoholic extract in mice,” Journal of Pharmaceutical & Health Sciences, vol. 1, no. 2, pp. 61–67, 2011.

S. Adisakwattana, T. Thilavech, and C. Chusak, “Mesona chinensis Benth extract prevents AGE formation and protein oxidation against fructose-induced protein glycation in vitro,” BMC Complementary and Alternative Medicine, vol. 14, no. 1, article 130, pp. 1–9, 2014.

R.-Y. Lin, R. P. Choudhury, W. Cai et al., “Dietary glycotoxins promote diabetic atherosclerosis in apolipoprotein E-deficient mice,” Atherosclerosis, vol. 168, no. 2, pp. 213–220, 2003.

M. Mobasseri, L. Payahoo, A. Ostadrahimi, Y. K. Bishak, M. A. Jafarabadi, and S. Mahluji, “Anethum graveolens supplementation improves insulin sensitivity and lipid abnormality in type 2 diabetic patients,” Pharmaceutical Sciences, vol. 20, no. 2, pp. 40–45, 2014.

Y. Takahashi, N. Inaba, S. Kuwahara, and W. Kuki, “Antioxidative effect of citrus essential oil components on human low-density lipoprotein in vitro,” Bioscience, Biotechnology and Biochemistry, vol. 67, no. 1, pp. 195–197, 2003.

H. A. Mudassir, M. B. Azmi, and S. A. Qureshi, “Phytochemical investigation of ethanolic seed extract of anethum graveolens and its effect on glucose tolerance in rabbits,” FUUAST Journal of Biology, vol. 1, no. 2, p. 41, 2011.

I. E. Orhan, F. S. Senol, N. Ozturk, S. A. Celik, A. Pulur, and Y. Kan, “Phytochemical contents and enzyme inhibitory and antioxidant properties of Anethum graveolens L. (dill) samples cultivated under organic and conventional agricultural conditions,” Food and Chemical Toxicology, vol. 59, pp. 96–103, 2013.

J. Bailer, T. Aichinger, G. Hackl, K. de Hueber, and M. Dachler, “Essential oil content and composition in commercially available dill cultivars in comparison to caraway,” Industrial Crops and Products, vol. 14, no. 3, pp. 229–239, 2001.

S. Reichert, D. Fischer, S. Asche, and A. Mosandl, “Stable isotope labelling in biosynthetic studies of dill ether, using enantioselective multidimensional gas chromatography, online coupled with isotope ratio mass spectrometry,” Flavour and Fragrance Journal, vol. 15, no. 5, pp. 303–308, 2000.

F. Sefidkon, “Essential oil composition of anethum graveolens,” Pajouhesh-va-Sazandegi, vol. 3, no. 2, pp. 73–77, 2012.

A. E. Al-Snafi, “The pharmacological importance of Anethum graveolens—a review,” International Journal of Pharmacy and Pharmaceutical Sciences, vol. 6, no. 4, pp. 11–13, 2014.

M. Mirhosseini, A. Baradaran, and M. Rafieian-Kopaei, “Anethum graveolens and hyperlipidemia: a randomized clinical trial,” Journal of Research in Medical Sciences, vol. 19, no. 8, pp. 758–761, 2014.