IOSR Journal Of Pharmacy (e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219 Volume 10, Issue 9 Series. I (September 2020), PP. 33-43 www.iosrphr.org A review on Nasturtium officinale: A potential medicinal plant Ali Esmail Al-Snafi Department of Pharmacology, College of Medicine, Thi qar University, Iraq. Received 17 September 2020; Accepted 02 October 2020 ABSTRACT: The chemical analysis of Nasturtium officinale showed the presence of alkaloids, flavonoids, saponins, terpenoids/steroids, protein, essential and volatile oils, glycosides, tannins, folic acid, vitamins and elements. The previous pharmacological studies revealed that Nasturtium officinale possessed hypolipidemic, antiinflammatory, hepato and reno protective, antidiabetic, antioxidant, anticancer, antimicrobial, dermatological, antigenotoxic, anti-urolithiatic and antigenotoxic effects. The current review highlighted the chemical ingredients and pharmacological effects of Nasturtium officinale. KEYWORDS: Nasturtium officinale, ingredients, pharmacology, therapeutic I. INTRODUCTION: Plants generally produce many secondary metabolites which are used as pharmaceuticals, agrochemicals, flavours, fragrances, colours, biopesticides and food additives. Recent reviews showed that the medicinal plants possessed wide range of biological effects included central nervous, cardiovascular, antioxidant, endocrine and reproductive, gastro-intestinal, respiratory, antidiabetic, antimicrobial, antiparasitic, dermatological, anticancer, anti-inflammatory, antipyretic, analgesic, immunological(1-20) and many other pharmacological effects(1-20). The chemical analysis of Nasturtium officinale showed the presence of alkaloids, flavonoids, saponins, terpenoids/steroids, protein, essential and volatile oils, glycosides, tannins, folic acid, vitamins and elements. The previous pharmacological studies revealed that Nasturtium officinale possessed hypolipidemic, anti-inflammatory, hepato and reno protective, antidiabetic, antioxidant, anticancer, antimicrobial, dermatological, antigenotoxic, anti-urolithiatic and antigenotoxic effects. The current review will highlight the constituents and pharmacological effects of Nasturtium officinale. Synonyms: Arabis nasturtium, Baeumerta nasturtium, Baeumerta nasturtium-aquaticum, Cardamine aquatica, Cardamine fontana, Cardamine nasturtium, Cardamine nasturtium-aquaticum, Cardaminum nasturtium, Crucifera fontana, Nasturtium aquaticum, Nasturtium aquaticum, Nasturtium fontanum, Nasturtium nasturtium, Nasturtium nasturtium-aquaticum, Nasturtium officinale subsp. rotundifolium, Nasturtium siifolium, Radicula nasturtium, Radicula nasturtium-aquaticum, Rorippa nasturtium, Rorippa nasturtium-aquaticum, Rorippa nasturtium-aquaticum, Rorippa officinalis, Sisymbrium amarum, Sisymbrium cardaminefolium, Sisymbrium fluviatile, Sisymbrium nasturtium, Sisymbrium nasturtium-aquaticum (21). Taxonomic classification: Kingdom: Plantae, Subkingdom: Viridiplantae, Infrakingdom: Streptophyta, Superdivision: Embryophyta, Division: Tracheophyta, Subdivision: Spermatophytina, Class: Magnoliopsida, Superorder: Rosanae, Order: Brassicales, Family: Brassicaceae, Genus: Nasturtium, Species: Nasturtium officinale(22). Common names: Arabic: HabbArreshad; Chinese: dou ban cai; English: Watercress, bronkors; French: cressond'eau; German: Brunnenkresse, echte Brunnenkresse; Indonesian: selada-air; Japanese: mizu-garashi, oranda-garashi; Portuguese: agrião; Spanish: berro(3). Distribution: Nasturtium officinale is native to Western Asia, India, Europe, and Africa, However, It is distributed in Africa (Algeria, Egypt, Libya, Morocco, Tunisia); Asia (Afghanistan, Iran, Iraq, Palestine, Jordan, Lebanon, Syria, Saudi Arabia, Turkey, Armenia, Azerbaijan, Georgia, Russian Federation, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan, India, Pakistan, Nepal, Sri Lanka, Indonesia, Malaysia, Philippines, China, Japan); Europe (Denmark, Ireland, Sweden, United Kingdom, Austria, Belgium, Czech Republic, Germany, Hungary, 33 A review on Nasturtium officinale: A potential medicinal plant Netherlands, Poland, Slovakia, Switzerland, Ukraine, Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Greece, Macedonia, Montenegro, Romania, Serbia, Slovenia, France, Portugal, Spain); Australasia (Australia, New Zealand); Northern America (Canada, Mexico, United States) and Southern America (Barbados, Cuba, Dominica, Dominican Republic, Guadeloupe, Haiti, Jamaica, Martinique, St. Lucia, St. Vincent and Grenadines, Trinidad and Tobago, United States, Guatemala, Nicaragua, Venezuela, Brazil, Bolivia, Ecuador, Peru , Argentina, Chile, Uruguay)(23). Description: It is perennial, rhizomatous, aquatic, 10-70(-200) cm tall, glabrous throughout or sparsely pubescent with simple trichomes. Stems 1-11 (-20) dm. Cauline leaves: petiole not winged, base auriculate; blade 3-9(-13)foliolate, (1-) 2-15(-22) cm; lateral leaflets sessile or petiolulate, rachis not winged, blade smaller than terminal; terminal leaflet (or simple blade) suborbicular to ovate, or oblong to lanceolate, (0.4-)1-4(-5) cm × (3-)7-25(-40) mm, base obtuse, cuneate, or subcordate, margins entire or repand, apex obtuse. Fruiting pedicels divaricate or descending, straight or recurved, 5-17(-24) mm. Flowers: sepals 2-3.5 × 0.9-1.6 mm; petals white or pink, spatulate or obovate, 2.8-4.5(-6) × 1.5-2.5 mm, (base to 1 mm), apex rounded; filaments 2-3.5 mm; anthers 0.61 mm. Fruits (0.6-)1-1.8(-2.5) cm × (1.8-)2-2.5(-3) mm; ovules (28-)36-60 per ovary; style 0.5-1(-1.5) mm. Seeds biseriate, reddish brown, ovoid, (0.8-) 0.9-1.1 (-1.3) × (0.6-)0.7-0.9(-1) mm, coarsely reticulate with 25-50(-60) areolae on each side(24-25). Traditional uses: It was eaten as a vegetable or salads. The leaves were widely used as a depurative, diuretic, expectorant, hypoglycaemic, hypolipidemic, odontalgic, stimulant, for the treatment of pulmonary diseases, hypertension and cardiovascular diseases(26-28). It was also used in abdominal pain, as anti-ulcerogenic, in the treatment of scurvy, tuberculosis, bronchitis, influenza and asthma (29-31). Physicochemical characteristics: The physicochemical properties of Nasturtium officinale extracts (%) were: moisture 98.39-99.53, dry material 0.5-1.61, ethereal extract 0.27-20.35, crude fiber12.06- 15.42, crude protein 33.51-47.91, ashes 13.6723.64 and carbohydrates 9.26-25.44g % (32). Chemical constituents: The preliminary phytochemical analysis of Nasturtium officinale showed that it contained alkaloids, flavonoids, saponins, terpenoids/steroids, , protein, essential and volatile oils, glycosides, tannins, folic acid, vitamin C, A, E and K, iodine, iron, potassium, sodium and calcium(33-36), Quantitative nutritional analysis of Nasturtium officinale showed that the plant contained (Quantity/80 g): calories 18 kcal, protein 2.4g, fat 0.8g, fiber 1.2g, β- carotene 2016 mcg, vitamin A equivalent 336 mcg, vitamin B1 0.13 mg, vitamin B6 0.18mg, vitamin C 50mg, vitamin E 1.17mg, folate 36mcg, vitamin K 200mcg, calcium 136mg, iodine 12mcg, iron 1.8mg, magnesium 12mg, manganese 0.5mg, phosphorus 42mg, potassium 184mg, zinc 0.6mg, selenium 1.6mcg. It also contained sodium 68.8mg/100g and copper 0.58 mg/100 g(37-38). Nasturtium officinale was a rich source of phenyl ethyl glucosinolate (PEGSL) and benzyl glucosinolate (BGSL), the precursors of phenyl ethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC). Glucosinolate, (gluconasturtin, 5.32 g of gluconasturtin/ 100 g of defatted seed) was the most abundant glucosinolate in Nasturtium officinale followed by the indole glucosinolates (glucobrassicin, 4-methoxy glucobrassicin, 4-hydroxyglucobrassicin and the aliphatic glucosinolate glucoibarin)(39-41). Sixteen compounds were isolated from the methanolic extract of Nasturtium officinale included [6-Ohydrocinnamoyl-bis(1-deoxy-1-thioβ-D-glucopyranosyl)-1,1′-disulfide; 3-O-hydrocinnamoyl-bis (1-deoxy-1thio-β-D-glucopyranosyl) -1,1′-disulfide; 2-O-hydrocinnamoyl-bis(1-deoxy-1- thio-β-D-glucopyranosyl) -1,1′disulfid; bis(1-deoxy-1-thio-β-Dglucopyranosyl)-1,1′-disulfide; indole-3-acetonitrile-4- methoxy-2-S-β-Dglucopyranoside; 8-(methylsulfonyl) octanonitrile;, 9-(methylsulfonyl) nonanenitrile; 7-(methylsulfinyl) heptanenitrile; 8-(methylsulfinyl) heptanenitrile; 9-(methylsulfinyl) heptanenitrile; syringing; sinapic aldehyde 4-O-β-D-glucopyranoside; 1-sinapoyl-β-Dglucopyranoside; 1,2-di-O-E-sinapoyl-β-gentiobiose; β-Dglucopyranoside-6-O-β-D-glucopyranosyl-1-[3-(4-hydroxy-3,5dimethoxyphenyl)2propanate] and lycibarbarphenylpropanoid C](42). Fourteen phenolic compounds were identified in the leaves included (gallic acid derivative, gallic acid derivative, ferrullic acid derivative, proanthocynidin B1, p-coumaric acid derivative, apigenin, phydroxybenzoic acid, sinapic acid, p-coumaric acid, caftaric acid, quercetin-3- (cafferoyldiglucoside)-7glucoside, kaempferol-3-(caffeoyl diglucoside)- 7-rhamnoside, caffeoylmalic acid, and coumaric acid derivative). In roots, a total of 20 compounds was identified included (gallic acid, gallic acid derivative, 34 A review on Nasturtium officinale: A potential medicinal plant hydroxybenzoic acid derivative, gallic acid, derivative, p-coumaric acid, p-coumaric acid derivative, caftaric acid, sinapic acid, pro-anthocynidintrimer, caffeic acid hexoside, caffeic acid derivative, sinapic acid glucoside, kaempferol-3- (caffeoyldiglucoside)- 7-rhamnoside, quercetin-3,7-diglucoside, hydroxybenzoic acid, vanillic acid, spincetine glucuronide, dihydro kaempferol hexoside, quercetin-3-O-rutinoside 7-O-glucoside and quercetin-3-O-triglucoside)(43). The total phenolic contents of aerial parts of Nasturtium officinale were 8.03 to 9.35 mgGAE in vegetative period and 6.5 to 7.65 mg GAE in generative period. While, the total flavonoids contents were 26.5 to 31.11 mg Qu E in vegetative period and 36.89 to 42.65 mg QuE in generative period(44). However, Nasturtium officinale water and ethanol extracts contained 88.60 ±2.41 and 74.18 ±1.72 µg pyrocatechol equivalent of phenolic compounds in 1000 mg, respectively(29). Many pigments were determined in the different parts of Nasturtium officinale. Lycopene in root, stem and leaves of Nasturtium officinale methanolic extract were 8.6, 16.4 and 17.5 mg/100 g, respectively. Chlorophyll-a contents in root, stem and leaves of Nasturtium officinale methanolic extract were 47.03, 59.1 and 85.6 mg/100 g, respectively, while, chlorophyll-b contents in the root, stem and leaves methanolic extract were 21.0, 28.2 and 31.0 mg/100 g, respectively. Furthermore, the β-carotene contents in the root, stem and leaves methanolic extract were 1.5, 4.3 and 15.0 mg/100 g, respectively(43). Anthocyanin in the petals of Nasturtium officinale was 71.67 mg/100 g, and pelargonidin 3sophoroside represented 91% of the total anthocyanin content (45). GC and GC/MS analysis of volatile constituents of the dried leaves and stems of Nasturtium officinale showed that the major volatile constituents of the leaves were 2-phenylethyl isothiocyanate (72.9%), pulegone (8.0%), heptylisothiocyanate (4.9%) and 4-phenylbutyl isothiocyanate (3.2%), while the main volatile constituents of the stems were 2-phenylethyl isothiocyanate (83.5%), 4-phenylbutyl isothiocyanate (6.9%), pulegone (2.2%) and sec-butyl isothiocyanate (1.9%)(46). The stems of Nasturtium officinale showed higher oil yield (1.5%) compared with leaves (1.2%) and flowers (1.0%) v/w. The essential oil of flowers of Nasturtium officinale contained 15 constituents, among which limonene (43.6%), α-terpinolene (19.7%), p-cymene-8-ol (7.6%) and caryophyllene oxide (6.7%) were the major components. Nine compounds were identified in the essential oil of the leaves. Myristicin (57.6%), terpinolene (8.9%) and limonene (6.7%) were the main components. Eight compounds were identified in the essential oil of the stem, caryophyllene oxide (37.2%), p-cymene-8-ol (17.6%), α-terpinolene (15.2%) and limonene (11.8%) were the most abundant(47). Pharmacological effects: Hypolipidemic effect: The effect of Nasturtium officinale hydroalcoholic extract (NOE) on serum lipid profile was studied in high-fat diet rats. Intragastric administration of the extract (500 mg/kg bw/day) lowered serum TC, TG and LDL-C by 34.2, 30.1, and 52.9%, respectively, and raised the serum HDL-C level by 27.0% after 10 days of treatments. The extract also reduced serum ALT and AST levels compared to high-fat diet groups(48). Intragastric administration of Nasturtium officinale (500 mg/kg bw/day) to groups of hypercholesterolaemic rats for 30 days lowered their blood total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels by 37, 44 and 48%, respectively. However, the blood high density lipoprotein cholesterol (HDL-C) levels was increased by 16%. Treatment of hypercholesterolaemic rats with Nasturtium officinale extract significantly increased the reduced glutathione level along with enhanced catalase and superoxide dismutase activities in liver tissues. In addition, Nasturtium officinale extract significantly decreased hepatic malondialdehyde level as well as glutathione peroxidase and glutathione reductase activities in extract-treated rats(49). Antiinflammatory effect: The topical anti-inflammatory activity of Nasturtium officinale leaves crude extract (solutions and gel) was investigated in irritant contact dermatitis induced by croton oil- in mice. Irritant contact dermatitis models were induced by a single (1 mg/ear; acute) or repeated (0.4 mg/ear; chronic; 9 days total) croton oil application. Nasturtium officinale extract and gel inhibited croton oil- induced ear edema, reduced the inflammatory cells infiltration and reduced the pro-inflammatory cytokines levels in acute and chronic model(50). In studying the anti-inflammatory effect of hydroalcoholic extract of Nasturtium officinale (250, 500 and 750 mg/ kg, orally) in two animal models of inflammation (carrageenan and formalin-induced paw edema) in rats, and the topical anti-inflammatory effect of Nasturtium officinale (2 and 5 mg/ear) in 12-Otetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. It appeared that the extract significantly inhibited carrageenan-induced paw edema 1, 2, 3 and 4 h after carrageenan challenge (P< 0.001). The extract (500 mg/ kg) also showed considerable activity against formalin-evoked paw edema over a period of 24 h 35 A review on Nasturtium officinale: A potential medicinal plant (P< 0.001). Histopathologically, the extract decreased swelling and the tissue damage induced by carrageenan. Topical application of Nasturtium officinale (5 mg/ear) reduced TPA-induced ear edema (P< 0.05)(51). Sixteen compounds isolated from the methanolic extract of Nasturtium officinale were evaluated for their inhibitory effects on nitric oxide (NO) levels in lipopolysaccharide (LPS)- stimulated murine microglia BV-2 cells. One of the isolated compounds (indole-3-acetonitrile-4- methoxy-2-S-β-D-glucopyranoside) possessed strong inhibitory effect on NO production, two other compounds (bis(1-deoxy-1-thio-βDglucopyranosyl)-1,1′-disulfide and β-D-glucopyranoside-6-O-β-D-glucopyranosyl -1- [3-(4-hydroxy-3,5dimethoxyphenyl)-2 propanate]) showed moderate inhibitory activities, suggesting the neuroprotective and antineuroinflammatory effects of bis-thioglycosides from Nasturtium officinale (42). Protective effect: The hepatoprotective and antioxidant activity of hydroalcoholic extract of watercress was evaluated against acetaminophen -induced hepatotoxicity in rats. The results showed that acetaminophen caused significant increase in aspartate amino transferase, alanine amino transferase, ferric reducing ability of plasma and protein carbonyl content. Furthermore, there was a significant reduction in total thiol levels and glutathione peroxidase activity in acetaminophen group compared to control. However, administration of the extract and silymarin significantly decreased aspartate amino transferase activity, and markedly increased total thiol content and glutathione peroxidase activity compared to acetaminophen group(52). The hepatoprotective effects of hydroalcoholic extract of watercress against oxidative stress and liver injury were investigated in bile duct ligation- induced cholestatic rats. Bile duct ligation considerably induced hepatocyte necrosis, this effect was significantly attenuated by the hydroalcoholic extract. Attenuation of liver damage in bile duct ligation- rats was associated with decreasing the hydroxyproline content and histopathological indexes. The extract also reduced oxidative stress by preventing the hepatic protein oxidation and enhancing the activity of the glutathione peroxidase (GPx) enzyme via antioxidative effect and free-radical scavenging(53). The protective effect of Nasturtum officinalis (twice a week for 31 days) on CCl4 induced nephrotoxicity was studied in rats. In treatment groups, after twenty one day and at the end of experiment, serum BUN, Alb, creatinine, blood urea and uric acid levels were significantly decreased in Nasturtum officinalis treated group compared with the control group(54). The protective effects of Nasturtium officinale hydroalcoholic extract (50, 100 and 200 mg/kg/day) against gentamicin -induced nephrotoxicity was investigated inr rats. The administration of gentamicin for 10 day increased urea nitrogen and creatinine and histopathological changes in kidney tissue. It was also caused oxidative stress and inflammatory process (increase in NO and TNF-α). Administration of Nasturtium officinale hydroalcoholic extract protected against deterioration in nephrotoxic markers and suppressed the increase in oxidative stress and inflammation markers(55). The effect of Nasturtium officinale hydro-alcoholic extract and vitamin E against vancomycin-induced nephrotoxicity was studied in adult rats. Vancomycin significantly increased serum creatinine and urea levels, MDA levels, relative kidney weight, as well as reduced creatinine clearance. The extract (250, 500 mg/kg) and vitamin E (500 mg/kg) pretreatment considerably alleviated all of these changes compared with vancomycin treated alone. Histological examination of vancomycin -treated group showed a marked renal injury with tubular epithelial cell desquamation, swelling, and tubular dilatation. These changes were mitigated with extract and vitamin E(56). The effect of the consumption of watercress (Nasturtium officinale), on acetaminophen metabolism, the pharmacokinetics of acetaminophen and its metabolites were studied in a crossover trial of human volunteers. The results showed that the consumption of watercress caused a decrease in the levels of oxidative metabolites of acetaminophen, probably due to inhibition of oxidative metabolism of this drug (31). The protective effect of Nasturtium officinale (25, 50 and 100 mg/kg, for 40 days) in oxymetholone induced oxidative testis injury was studied in mice. 100 mg/kg of Nasturtium officinale extract significantly reduced the serum level of testosterone and significantly increased the levels of LH and FSH in comparison with the control group. At the same dose, it also significantly improved the stereological factors and sperm parameters. 50 and 100 mg/kg of Nasturtium officinale extract significantly increased the testis tissue ferric reducing ability of power (FRAP) levels, and 100 doses reduced the serum levels of NO (57). The protective effect of Nasturtium officinale juice (orally, 0.5 and 1g/kg bw, for 15 consecutive days before intraperitoneal injection of cyclophosphamide 100 mg/kg bw) was studied in cyclophosphamide induced oxidative stress in mice. Intake of watercress prior to cyclophosphamide administration enhanced superoxide dismutase activity in erythrocytes with no effect on catalase activity. Watercress juice counteracted the effect of cyclophosphamide in bone marrow and liver tissues. Glutathione was increased by watercress supplementation and lipid oxidation was diminished compared to untreated groups(58). 36 A review on Nasturtium officinale: A potential medicinal plant The effects of hydroalcoholic extract of Nasturtium officinale (500mg/kg, bw) on blood cells and antioxidant enzymes were studied in rats exposed to sodium (meta) arsenite (5.5mg/kg of bw of NaAsO2). WBC, RBC and Hct were decreased in the rats exposed to NaAsO2 (P<0.05). A significant increase was seen in RBC and Hct after treatment with the plant extract (P<0.05), The extract also elevated the antioxidant capacity, which significantly declined by NaAsO2(59). Antidiabetic effect: The hypoglycemic effect of Nasturtium officinale extracts was evaluated in streptozotocin induceddiabetic rats. Rats were orally administered with various concentrations of Nasturtium officinale extracts (ethyl acetate, methanol and aqueous) for short (one week) and long period (two months). Only 800 and 1000 mg/kg of the methanol extract of Nasturtium officinale caused a significant decrease in the blood glucose level after one week treatment. At the end of two months treatment, ethyl acetate extract significantly reduced blood glucose level at 100 mg/kg. Long period treatment with methanol and aqueous extracts showed no hypoglycemic effects(60). The hypoglycemic and antioxidant activities of orally administered aqueous, acetonic, and alcoholic extracts of Nasturtium officinale were studied in alloxan and streptozotocin induced diabetic rats. Extracts showed high concentrations of phenols, polyphenols, and flavonoids, in addition to a very high antioxidant effect. The hypoglycemic effect of the aqueous upon acute administration was 76.6% higher than that of insulin. When administered chronically, glucose levels were normalized on the third week up to the eighth week, and the antioxidant enzymes and biochemical parameters were improved(32). The effect of oral administration of Nasturtium officinale [plant-mixed pelleted food (6.25%) for 6 weeks, orally] on serum glucose and lipids, as well as morphology of Langerhans islets was investigated in streptozotocine induced- diabetic rats. Nasturtium officinale feeding caused significant hypoglycemic effect (P<0.01), but it caused no significant changes in the serum total cholesterol, HDL- and LDL-cholesterol levels in treated diabetic group as compared to untreated diabetic group. Furthermore, treated diabetic group showed a significant lower level of serum triglyceride as compared to untreated diabetic group (P<0.05). Histological study showed that Nasturtium officinale feeding caused no beneficial effect in Langerhans islets, regarding the number of beta cells(61). The antidiabetic and antihyperlipidemic effects of the hydroalcoholic leaf extract (daily in drinking water for 4 weeks) of Nasturtium officinale were investigated in streptozotocin-induced diabetic rats. There was a significant increase in serum glucose, triglycerides, total cholesterol, and LDL in streptozotocin-induced diabetic rats, accompanied by a decrease in HDL. The hydroalcoholic leaf extract of Nasturtium officinale significantly reduced serum glucose, total cholesterol and LDL in comparison with untreated diabetic rats (62). Antioxidant effect: Nasturtium officinale extract possesses potent reducing power in a ferric reducing antioxidant power assay, concentration-dependent scavenging ability on 2,2'-azinobis 3-ethylbenzothiazoline-6-sulfonate, 1,1diphenyl-2-picrylhydrazyl, nitric oxide radicals, and hydrogen peroxide, in addition to chelating effect on ferrous ions. The extract also dose-dependently prevented thiobarbituric acid reactive substances formation in ferrous ion/ascorbate induced lipid peroxidation in rat liver homogenate(63). The Anti-radical properties and the phenolic, flavonoid, and anthocyanin contents of the watercress hydroalcoholic extract was examined by using the radical scavenging activity test of DPPH. The hydroalcoholic extract obtained by soxhlet showed more potent antioxidant activity than the incubated extract, and had more phenolic and flavonoid compounds. The IC50 value of the hydroalcoholic extract of watercress was 105.20± 2.28 µg/ml for the soxhlet extract and 108.68± 5.41 µg/ml for the incubated extract (64). The antioxidant effect of the ethanolic extract of the leafy stems of Nasturtium officinale was investigated in vitro using DPPH radical scavenging test. The extract of Nasturtium officinale at the concentration of 10 mg/ml, showed low reducing power (I%=3.396%, IC 50=11.60 mg/ml) compared to ascorbic acid (I%= 92.62%, IC50=0.89 mg/ml), but it increased at the dose of 100 mg/ml (I%=60.38%)(65). The antioxidative properties of aqueous and ethanolic extracts of the leaf of Nasturtium officinale were evaluated using in vitro and in vivo tests. The ethanolic extract showed more antioxidant activity, reducing power, DPPH radicals and superoxide anion radicals scavenging activities. Administration of the ethanol extract to rats decreased lipid peroxidation in liver, brain and kidney(29). The antioxidant activity of Nasturtium officinale essential oil was evaluated using DPPH. The essential oil possessed antioxidant effect less than BHT, when tested at concentrations of 50, 100, 200, 300, 400, 500 and 1000 ppm. It gave inhibition of 37.99% at concentration of 1000ppm compared with 93.75% inhibition for BHT at the same concentration(66). Nasturtium officinale extracts and oils were investigated for antioxidant activities using DPPH and β-carotene-linoleic acid assays. Methanol extracts of leaves showed higher antioxidant activity than the oils and 37 A review on Nasturtium officinale: A potential medicinal plant methanol extracts of stems and flowers. Compared with essential oils and methanol extracts, the leaves polar sub-fraction of methanol extract possessed the highest antioxidant activity (IC50 = 20.1 0.3 mg/ ml), which was comparable to that of the synthetic antioxidant BHT (18.0 0.3 mg/ ml ) (47). The antioxidant activity of aerial parts of Nasturtium officinale at various altitudes and periods of growth was investigated in vitro. The highest antioxidant activity and radical scavenging effect were observed in the aerial parts of the plant in vegetative period, whereas, aerial parts of the plant in generative period showed weak antioxidant activity(44). The antioxidant efficacy of various organic solvent extracts of watercress was evaluated by DPPH free radical scavenging assay. Methanolic extract of watercress showed the best antioxidant activity in comparison with ethyl acetate and hexane extracts(33). The possibility of watercress to reduce cancer risk by inducing detoxification enzymes was investigated using human peripheral blood mononuclear cells (PBMC). Watercress showed ability to modulate the enzymes SOD and GPX in blood cells in vitro and in vivo(67). A randomized controlled investigation was designed to test the attenuating effect of consumption of watercress supplementation (acute: 2h before exercise) and ( chronic: 8 weeks consumption) on exerciseinduced oxidative stress. Each subject completed an incremental exercise test to volitional exhaustion following chronic and acute watercress supplementation or control. The results showed an exercise-induced increase in DNA damage and lipid peroxidation over both acute and chronic control supplementation phases, while acute and chronic watercress attenuated DNA damage and lipid peroxidation and decreased H 2O2 accumulation following exhaustive exercise (P<0.05 vs control). A marked increases in the main lipid-soluble antioxidants (atocopherol, g-tocopherol and xanthophyll) were observed following watercress supplementation (P<0·05 vs control) in both experimental phases(68). Anticancer effect: The anticancer effect of the watercress hydroalcoholic extract was studied against the growth of cancerous Hela cells, and fibroblasts. The extract was applied at concentrations from 0.625 to 2 mg/ml, and cell mortality rates were examined after 24, 48, and 72 h incubation. The survival rate of the cancerous Hela cells was decreased with time and increasing concentrations of watercress extract. IC50 values after 24, 48 and 72 h were 373, 349, and 333 µg/ml, respectively(64). The effects of daily intake of an aqueous solution of watercress on the growth of the experimental Ehrlich tumor was investigated in mice. Mice showed a suppression of tumor growth and a small area of necrosis compared to the control(69). The chemoprotective effects of crude watercress extract against three important stages of the carcinogenic process, [initiation, proliferation, and metastasis (invasion)] were studied using in vitro models. HT29 cells were used to investigate the protective effects of the extract on DNA damage and the cell cycle. The extract was not genotoxic but inhibited DNA damage induced by two [hydrogen peroxide and fecal water] of genotoxins, indicating that it inhibited initiation. The extract also caused an accumulation of cells in the S phase of the cell cycle, which indicated cell cycle delay at S phase. The extract also significantly inhibited invasion of HT115 cells(70). Phenylethyl isothiocyanate inhibited the migration and invasion of human colorectal carcinoma cells and inhibited the proliferation of cancer cells. Phenylethyl isothiocyanate also decreased matrixmetalloprotease-9 and ALDH1 marker of human breast cancer and also inhibit tumor invasion (71-73). A single-blind, randomized, crossover study was performed to, determine the effects of watercress supplementation on biomarkers related to cancer risk, in healthy adults (fed 85 g raw watercress daily for 8 wk in addition to their habitual diet). Watercress supplementation ameliorated the DNA damage and increased the blood antioxidant potential in human subjects(74). The effects of watercress consumption on the metabolism of nicotine in smokers were examined. Watercress was a rich source of phenethyl isothiocyanate (PEITC), an effective chemopreventive agent for cancers of the lung and esophagus induced in rodents by nitrosamines, including the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (75-76). Antimicrobial effect: The antibacterial effect of aqueous and alcoholic extracts of Nasturtium officinale was studied against Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and Listeria monocytogenes. The antibacterial activity of the alcoholic and aqueous extracts of Nasturtium officinale was higher against Grampositive bacteria than Gram-negatives. S. aureus and L. monocytogenes were the most sensitive bacteria with MIC of 8 μg/ml. the lowest MIC (6.25 μg/ml) and MBC (12.5 μg/ml) of the plant extract were recorded against S. aureus. While, E. coli and S. typhimurium resisted the aqueous and alcoholic extracts(77). 38 A review on Nasturtium officinale: A potential medicinal plant The antibacterial activities of Nasturtium officinale essential oil were investigated against some important food borne bacteria (Gram positive bacteria: Staphylococcus aureus and Bacillus cereus, and Gram negative bacteria: Escherichia coli and S. enteric). S. enteric and E. coli were the most resistance, and B. cereus isolates were the most sensitive to the essential oil(66). The methanolic extract of Nasturtium officinale was tested for its antimicrobial activity against Bacillus cereus, Enterococcus faecalis, Klebsiella pneumonia and Escherichia coli. The MICs of the extract against these microorganisms were 0.6, 0.4, 0.8 and 0.6, while MBCs were 0.10, 0.8, 0.10 and 0.8 mg/ml, respectively(78). The antimicrobial activities of silver nanoparticles (Ag-NPs) of leaves aqueous extract of Nasturtium officinale was studied against the growth of Gram-positive (S. aureus). The inhibition was observed in the AgNPs against S. aureus. The results showed that most of S. aureus was damaged and extensively disappeared by the addition of Ag-NPs(79). The in vitro synergism between aqueous and methanolic extracts of Nasturtium officinale and 2phenylethyl isothiocyanate, identified in Nasturtium officinale, with standard antibiotics, was carried out against 11 isolates of extended-spectrum β-lactamases-Escherichia coli. The results showed that there was an increase in antibacterial activity of the antibiotics when they were combined with plants extracts and 2-phenylethyl isothiocyanate(80). Dermatological effect: The wound healing potential of watercress oil in thermal and chemical burn injuries was studied in rabbits. Watercress oil was applied to the experimental chemically and direct heat induced burns. Animals treated by watercress oil restored the normal architecture more rapidly with significant reduction in closure time of burn(81). Protective effects of indole 3-acetonitrile-4- methoxy -2- S-β-d-glucopyranoside (IAMG) from Nasturtium officinale was studied against ultraviolet B-induced photodamage in normal human dermal fibroblasts. The results showed that IAMG enhanced human dermal fibroblast cell migration. The UVB-induced increases in MMP-1 and decrease in type I procollagen which were ameliorated by IAMG treatment. The result strongly suggested that IAMG from Nasturtium officinale reduced UVB-induced photodamage(82). Anti-urolithiatic effects: The protective effects of hydrophilic extract of Nasturtium officinale (750 mg/kg and 1.5 g/kg of extract) on ethylene glycol-induced renal stone was studied in rats. Percentage of calcium oxalate crystals in negative control groups was 75%, in preventive groups treated with low dose (28.6%) and high dose (57.1%) in comparison to healthy control group (12.5%). Urinary oxalate concentration in preventive and negative control groups were more than healthy control group (P< 0.05)(83). Antigenotoxic effect: The effect of aqueous extract (two concentrations :13.2 and 26.4 mg/ml) on cell viability and its potential antigenotoxic properties against induced oxidative damage was studied using a comet assay and peripheral blood cells as an in vitro model. No differences were found in cell viability between the control and treated groups at any time. Significant antigenotoxic effects were observed for both concentrations (p = 0.005 at 30 min; P< 0.001 at 60 and 90 min), the percentage reductions in damage being similar between the concentrations used (67.1 and 75.2% respectively)(84). Side effects and toxicity: The in vivo acute toxicity was studied in mice. During the acute oral toxicity, the plant extract exerted a stressful effect on mice at different doses, especially at doses of 80 mg/kg and 100 mg/kg. Some clinical signs were recorded within eight hours after gavage included strong agitation followed by immobility. Several deaths were observed after 72 hours with an LD50 ranged between 50 and 500 mg/kg bw(45). The safety of the standardized extract of Nasturtium officinale with phenylethyl glucosinolate 5.0 mg/ml was studied using acute and sub-acute oral dosage in rats. LD50 was in the range of 2-5g/kg. The results revealed that Nasturtium officinale extract at dose up to 5 g/kg in acute study was safe, and no adverse effects were observed in the subacute administration, up to 1 g/kg( 51, 85). However, the acute toxicity of ethanolic extract (0,5, 5, 50, 500, 1000, 2000, and 4000 mg/kg bw) of Nasturtium officinale was studied in mice. The maximal dose caused no deaths, animals were still in normal circumstances. No significant differences in relative organ weights liver, heart, kidneys in mice a in all doses. 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