ERUCA SATIVA LINN.: PHARMACOGNOSTICAL AND PHARMACOLOGICAL PROPERTIES AND PHARMACEUTICAL PREPARATIONS

Eruca sativa (jarjeer) is an annual herb (family Brassicaceae), which contains a wide range of chemicals and minerals with nutraceutical and organoleptic characteristics. Jarjeer was generally used as a food and traditionally mainly consumed due to its aphrodisiac properties. This crop known to contain various phytochemicals such as flavonoids, phenolic acids, terpens, carotenoids, tannins, glycosides, saponins, sterols, alkaloids, and other secondary metabolites. In leaves, kaempferol and its derivatives, glucosativin, are the main flavonoids and glucosinolate, respectively, while erucic acid and glucoerucin are the main fatty acid and glucosinolate, respectively. Medicinally, the plant has antibacterial, antidiabetic, antihypertensive, antiplatelet, and antioxidant activity and stimulates hair growth and other effects. Trails on topical pharmaceutical preparations involve the use of E. sativa which had been done. These preparations include creams and waxs which are intended to be used for potentiating hair growth and skin fungal and bacterial infection.

Ferulic acid, coumaric acid, vanillin, resorcinol, and catechol are detected in leaf extract by HPLC, and gallic acid was detected in aqueous leaf extract by high-performance thin-layer chromatography. Ellagic, tannic, and gallic acid; quercetin kaempferol; rhamnetin, quercetin triglucoside; rutin, monosynapoyl triglucoside; and kaempferol-3-O-galactoside were the phenolics detected in E. Sativa seed extract. Resorcinol and catechol, benzoic acid, ellagic acid, quercetin, and rutin are detected in flower extract by HPLC [6,35,44,45,50,51]. In rocket adult roots, the flavonoid level was very low and therefore not identified. E. sativa flowers had a very complex anthocyanin (phenolic compounds) profile which was not completely described by LC-MS [52]. The chemical structure of the main flavonoids in E. sativa is shown in Fig. 1.
Glucosinolates as β-thioglucoside, N-hydrosulfates in the presence of myrosinase, are hydrolyzed forming isothiocyanates, nitriles, thiocyanates and other hydrolytic products depend on pH and other factors.

Antiulcer effect
Antiulcer effect of E. sativa is known in traditional medicine. Helicobacter pylori which are involved in the pathogenesis of ulcer have a high urease activity, and urease enzyme is essential to H. pylori metabolism and required for its colonization in gastric mucosa. E. sativa extract produces a marked reduction of urease activity and thus provides scientific confirmation for its use as antiulcer agent [63].
In experimentally induced gastric lesions, rocket extract has cytoprotective, anti-secretory, and anti-ulcer actions. The anti-ulcer activity may be mediated through an increase in prostaglandin, mucous synthesis, and-or antioxidant activity by inhibiting lipid peroxidation.
Phytochemicals reported in rocket leaves such as flavonoids, sterols, and/or triterpenes are well known for their antioxidant actions, to which anti-ulcer mechanisms may be attributed [64,65].

Antioxidant effect
Lipid autoxidation is initiated by a chain of lipophilic radicals. In vivo hydrogen peroxide (H 2 O 2 ) is generated by several oxidase enzymes. H 2 O 2 through hydroxyl free radical serves as a messenger molecule in the inflammatory mediators' synthesis and activation; these mediators are involved in tissue damage and pathogenesis of various diseases such as diabetes [66].
E. sativa flower extract is a powerful antioxidant. 1, 1-diphenyl-2picrylhydrazyl free radical scavenging test and β-carotene bleaching test were used to estimate the antioxidant effect of flower extract [67]. The concentration of phenolics in leaves is 6 times more than that of rocket stems; kaempferol 3,4-di-O-glucoside, kaempferol 3-glucosyl, quercetin 3-glucosyl, and isorhamnetin 3-glucosyl are the main phenolics in rocket leaves and proved to be a powerful antioxidant [68]. Seed extract contains significant levels of phenolics, these phenolics are considered as natural antioxidant through free radical scavenging or quenching effect. Furthermore, rocket seeds contain significant levels of glucosinolates, especially glucoerucin, which demonstrates the antioxidant effects through phase II enzymes induction, by scavenging hydrogen peroxide and alkyl hydroperoxides gathered in cells and peripheral blood and by serving as a precursor of sulforaphane, a powerful inducer of detoxifying enzymes [69]. The activity of natural antioxidants is less than that of synthetic antioxidant [66].
Antibacterial effect E. sativa seed extract has a potent antimicrobial activity, considering it as a promising antibacterial agent against resistant Gram-negative (G-ve) and Gram-positive (G+ve) bacteria [70] which confirm its use as a remedy in traditional medicine for the management of urinary, skin infections, fever, and diarrhea. The bioactive compounds, erucic acid, and isothiocyanates are responsible for antibacterial effect [7].  [71]. It was found that extracts of E. sativa seeds had a remarkable antibacterial action against S. aureus and B. cereus [72]. Eruca seed oil also exerts antibacterial and antifungal effects [73].

Effect on fertility
Since Roman times, rocket was recognized as a powerful aphrodisiac remedy [74]. Ethanolic extract of E. sativa was reported to have an androgenic action or induce testicular steroids production which stimulates the preputial gland, as well it enhances spermatogenesis in the male mice testis [75]. A considerable rise in testosterone hormone level and sperm activity was attributable to the extract of rocket leaves; furthermore, a significant reduction in sperm death and abnormalities was observed. The existence of saponins and alkaloids in rocket extract produce a significant enhancement in sperm activity. On comparison to the control group, histological sections of seminiferous tubules showed a significant increase in diameter of these tubules, spermatids, and Leyding cells and reduction in interstitial space was observed after five weeks of using with E. sativa extract. This increment might be attributed to the ability of rocket extract to activate testes growth and enhancement of spermatozoa proliferation, maturation, and differentiation as compared with the control group [76]. Rocket seed oil showed a protective effect against nicotine-induced testicular damage by reversing (almost entirely) all morphometric and histological modifications in testis caused by nicotine [77].
Both Eruca leaves and seeds have aphrodisiac effect. In seeds, the aphrodisiac effect may be attributed to desulfoglucosinolates, erucic acid, and an essential oil that is rich in isothiocyanates or to a combination of these phytochemicals [78].
Mona et al. in their study revealed that small doses of seeds oil stimulate spermatogenesis, while large doses suppress spermatogenesis possibly due to erucic acid high content [79].

Hepatoprotective effect
Ethanolic and aqueous rocket leaf extracts demonstrate hepatoprotective effect against carbon tetrachloride, phosphoric acid, and paracetamol-induced liver toxicity [11,20,25]. The liver toxicity is due to free radicals that have the ability either for proteins binding or abstracting a hydrogen atom from unsaturated molecules of lipid, and hence, accelerating or fastening lipid peroxidation and toxic effect. El-Nattat and ElKady said that the activities of alanine aminotransferase and aspartate aminotransferase are promoted due to rocket administration in male rabbits, and this probably attributed to the high sulfur content in rocket that expels body wastes. E. sativa leaves and seeds significantly restore non-protein sulfhydryl level in liver tissue, supporting or assisting the liver and immune function.
The possible hepatoprotective activity of ethanolic rocket extract may be due to the suppression of the cytochrome P450 oxygenase enzyme system and glucoerucin (the major glucosinolate in rocket) which has indirect and direct antioxidant actions in addition to hydroperoxides and H 2 O 2 decomposition properties [11,80].

Hyperlipidemic effect
The major cause of atherosclerosis which is highly correlated to ischemic heart disease is hypercholesterolemia and hypertriglyceridemia [81]. E. sativa leaf extract possesses antihyperlipidemic and antihypercholesterolemic effects [82]. The antihyperlipidemic action of rocket leaf extract perhaps due to Vitamin C activation of the 7alpha-hydroxylase enzyme. E. sativa leaves conations Vitamin C, which promotes plasma cholesterol conversion into bile acid, as a result subsequent decrease in serum cholesterol levels, additionally the capacity of the Vitamin C to prevent the oxidation of high-density lipoprotein [23]. The rocket oil hypocholesterolemic effect perhaps due to the phytosterols; β-sitosterol, campasterol and beta-amyrine.
(these sterols decrease cholesterol concentration by preventing its absorption and inactivation of the hepatic cholesterol esterase) or due to high ratio of unsaturated fatty acids which decrease lipoproteins Jaafar and Jaafar production. Phytosterols reduced the dietary and biliary cholesterol conjugation into micelles, and this depresses cholesterol absorption. Synthesis of cholesterol and low-density lipoprotein (LDL) receptors activity is increased, which eventually leads to reduced serum LDLcholesterol concentration. The rocket oil hypocholesterolemic effect is better than that of olive oil [82,83]. Hence, rocket oil decreases the total cholesterol, total lipid, and LDL concentration and can be considered as worthy source for omega fatty acids and might be consumed as a healthy oil to minimize saturated oil consumption. Saturated oils and fats are the reasons for the development of several chronic illnesses [84].

Antihypertensive effect
Rocket had been utilized as a remedy in traditional medicine for managing the cardiovascular complaints, particularly hypertension [85][86][87]. Oral and intravenous administration methanolic extract of rocket aerial parts and its fractions (especially aqueous fraction) demonstrates hypotensive effect in normotensive and hypertensive rats (hypertension is induced by high salt diet). The antihypertensive effect is the net result of vasodilatory and cardiotonic effects. Vasodilatory mediators, as nitric oxide and certain muscarinic receptors existing on vascular endothelial cells, are implicated in vasodilation. Activation of these receptors ultimately leads to nitric oxide production. Rocket extract also has a direct influence on vascular smooth muscle in rat. Crude extract and, especially, ethyl acetate fraction are loaded with flavonoids and phenols; previous studies revealed that the flavonoids and phenols have anticholinesterase and cardioprotective effects and may be implicated in hypotensive effect. Erucin (also major component of rocket) is produced from sulforaphane metabolism. Sulforaphane is known with potential hypotensive effect, so the antihypertensive effect is possibly due to quercetin, erucin, and other rocket constituents [88].

Antidiabetic effect
Rocket seeds and leaves ameliorate hyperglycemia and produce antidiabetic effect [89][90][91]. E. sativa seed oil has powerful antihyperglycemic and antihyperlipidemic actions in streptozotocin (STZ)-induced diabetic rats. High glucose concentration yields reactive oxygen species (ROS) due to autoxidation, metabolism of glucose, and the development of advanced glycosylation end products. ROS activates lipid peroxidation that causes devastation and injury to the cell membrane; lipid peroxidation is one of the distinctive features of chronic diabetes.
The protective effects of rocket seeds oil against hyperglycemia and hyperlipidemia probably as a result of their ability to modulate the pancreatic islets architecture, antioxidant activity (through free radical scavenging activity), increasing (glutathione and superoxide dismutase concentration) and insulin secretory response [92,93].
E. sativa extract shows suppressing effect on carbohydrate metabolism through inhibition of carbohydrate-hydrolyzing enzymes, α-amylase, α-glucosidase, and β-galactosidase in dose-dependent manner. Aqueous extract exhibited less inhibitory effect than ethanolic extract on carbohydrate metabolism [91].
Oral administration of rocket leaves extract in STZ-induced diabetic rats greatly retrieves the abnormal parameters in experimental animals. Hence, E. sativa may be valuable for patients who suffer from diabetes [94].

Antifungal effect
Rocket leaf oil that extracted by steam distillation has significant antifungal effect assessed by well-diffusion method. The extracted oil has a high rate of inhibition (60-67%) against Dreschlera halodes, Cola clavata, Rhizopus oryzae, and Aspergillus nidulans. While the oil moderately suppress Alternaria kiliense (49%), Alternaria alternata (38%) and exhibited minimum inhibition against F. oxysporum with (13%) [14]. Powdered seeds of E. sativa demonstrate antifungal effect. Crude aqueous seeds exhibited strong powerful antifungal effect against the fungus Spadicoides stoveri and Paecilomyces variotii while insignificant inhibition against other fungal strains [95].

Anti-inflammatory and antiedema effect
Rocket seeds are used by traditional herbalists for the management of rheumatoid arthritis. Abodola et al. designed a study to assess the antiinflammatory effect of Eruca seeds, and his study revealed that ethanolic seed extract demonstrates a dose-dependent sustained anti-edema action superior to indomethacin. The anti-inflammatory effect of seeds possibly mediated through flavonoids as quercetin and isorhamnetin, also to 4-methylthiobutyl isothiocyanate (main isothiocyanates in seeds). 4-methylthiobutyl isothiocyanate inhibits the expression of pro-inflammatory genes, tumor necrosis factor-alpha, and some other interleukins (ILs). Non-steroidal anti-inflammatory drugs are known for their deleterious effect on gastric mucosa, while E. sativa extract has gastroprotective effect. Large doses of rocket may cause anaphylaxis and immunosuppression [96].

Nephroprotective effect
Rocket is generally used in traditional medicine as a remedy for renal disease. Elgazar and his colleague proved that E. sativa induced diuresis and has nephroprotective effect against gentamicin-induced nephrotoxicity in rats [97,98].
The rocket alsoholic seed extract has nephroprotective action in mercuric chloride (HgCl 2 )-induced nephrotoxicity. This protective effect due to the ability of seed extracts of E. sativa for rising or maintaining the antioxidant molecules and antioxidant enzymes levels in the kidney and through the protective effect to kidney, thereby protect the tissues against oxidative damage. Flavonoids and glucoerucin present in rocket seeds extract may be involved in nephroprotective activity [99].
Hussien proved in his study that the aqueous extract of E. sativa successfully prevents the occurrence of nephrocalcinosis in rabbits through suppression calcium oxalate crystal formation and deposition in renal tissues. Prevention of nephrocalcinosis of rocket is due to its diuretic effect and alkalization of urine (calcium oxalate crystals deposing is enhanced in acidic urine). Furthermore, E. sativa has a large amount of magnesium, and thus, it may lessen free oxalate in intestine and urine, reducing its availability for binding to Ca ion in renal tubules, and thus, calcium oxalate crystal formation is suppressed [100][101][102].

Antiplatelet effect
Platelets activation has a role player in the development of acute thrombus and cardiovascular diseases. Hydroalcoholic extract of rocket leaves exhibited antiplatelet effect (both in vivo and in vitro); as it prevents thrombus formation without significant risk of bleeding. E. sativa extract restrains thromboxane B2, tissue growth factor (1β), and IL-1β which are platelet inflammatory mediators, and these mediators participate in the development of atherosclerotic lesion and arterial thrombogenesis. Human platelet CCL5 levels which are induced by adenosine diphosphate also inhibited by E. sativa extract but lo lesser extent. These effects ultimately prevent thrombus development. E. sativa Mill antiplatelet activity could be explained by the existence of kaempferol, quercetin, and isorhamnetin. Kaempferol derivatives are the major phenolics in rocket leaves [103].

Other effects
A mixture of milled seeds of E. sativa and cream was applied on the face for its antiacne effect [104]. Lotion of E. sativa promotes hair regrowth and reverse greasy scalp [105]. Orally administered mixture of seeds oil and sugar is used for the treatment of dysentery [106].
Shatalebi et al. studied the development of an oil/water (o/w) hair wax formulas for hair growth containing ethanolic extract E. sativa seed oil, with the aid of thickening agents in different concentrations.

Jaafar and Jaafar
The resultant formulations were evaluated and compared to brand marketed product. Best results were observed with formula containing 10% ethanolic extract of propolis and 10% E. sativa seed oil. This formula increased the hair length, the newly grown hairs weight, and improved percentage phase of hair follicles [107].
Sanad et al. formulated and evaluated enriched garlic and Eruca oils stable cream with antibacterial activity. Different formulations were prepared using different concentrations of two surface active agents. Cream prepared with 2% surfactant mixture showed well-designed formulation and best antimicrobial activity [108].
Taha et al. formulated a new herbal antifungal hair cream containing Eruca and garlic oils, active on pathogenic fungi (Malassezia furfur, Microsporum canis Bodin, and Trichophyton mentagiophytes) using different ratios of non-ionic surfactant. Highest permeation rate of alliin in the presence of Eruca oil which is necessary for antifungal activity was obtained with formula of 4% concentration of Span and Brij [109].

CONCLUSION
Plants and herbal extracts constitute a vital position in modern medicine; E. sativa is an important nutraceutical that has diverse phytochemicals. Although the plant was excessively studied and many compounds have been isolated, further studies are required to support the traditional uses of plant. Scientific research should be employed to isolate, elucidate, and specify the chemical structure of each compound responsible for specific pharmacological action. In addition, more pharmaceutical studies should be employed to formulate more dosage forms containing the active constituents of E. sativa due to broad pharmacological activity of them.