Journal of Medical Pharmaceutical www.jmpas.com And Allied Sciences ISSN NO. 2320 - 7418

REVIEW ARTICLE Correspondence Unnati shah Department of Pharmacognosy, ON POISONOUS PLANT BUT Pioneer Pharmacy degree college, MEDICINALLY ACTIVE- vadodara, India. Email Id: ARGEMONE MEXICANA [email protected] Keywords * Bhatt Mehul, Shah Unnati Argemone Mexicana, Poisonous plant, Agricultural Pioneer Pharmacy Degree College, Vadodara. India weed, Toxicity study. Received 05 November 2014 Reviewed 10 November 2014 Accepted 11 November 2014

ABSTRACT Argemone mexicana Linn (Papaveracea) is commonly known as ‘Mexican prickly poppy’ and ‘Satyanashi’ is a common name, it is a well-known weed in the agricultural and waste lands. It is a widely distributed plant throughout the subtropical and tropical regions of the world. Argemone mexicana Linn has been reported to possess Anti-malarial, Antibacterial, Wound healing, Antiasthma tic, Hepatoprotective, Anti-HIV, Vasorelaxant activities. The present article reviews the pharmacological and phytochemical work done on the plant and determines a scientific base for novel study for future research to establish toxin free response of plant or its phytoconstituents.

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INTRODUCTION Argemone mexicana Linn (Papaveracea) is commonly known as ‘Mexican prickly poppy’ and ‘Satyanashi’. It occurs as wasteland weed in almost every part of India. In many parts it is repoorted as crop weed also. The genus Argemone includes 12 species. According to Ayurveda the plant is used as diuretic, purgative and destroys Morphological description worms. In Homoeopathic system of It is a prickly, glabrous, branching herb with medicine, the drug prepared from this herb yellow juice and showy yellow flowers, The is used to treat the problem caused by tape- Sanskrit name svarnakshiri is given because worm. The plant contains alkaloids as of the yellow juice (Svarna - Gold; Kshiri - berberine, protopine, sarguinarine, optisine, Juice). The height of this plant varies chelerytherine etc (1). between 0.3 to 0.12 meters, Leaves are Taxonomical classification: thistle like. Stem clasping; Oblong, sinuately Kingdom: Plantae pinnatifid, spinous and viens are white. Divison: Angiosperm Sub division: Eudicots Flowers are terminal, yellow and of 2.5–5.0 Order: Ranunculales cm diameter. Fruits are capsule. Prickly and Family: Papaveraceae Genus: Argemon oblong ovoid. Seeds numerous, globose, Species: A. mexicana netted and brownish black. Flowering time Vernacular names: is all round the year in Indian conditions. Hindi: Shialkanta, Satyanashi Gujrati: Darudi Useful Parts: Roots, leaves, seeds and Danarese: Balurakkisa, Datturi, Pirangi, datturi yellow juice. Marathi: Daruri, Firangi-kote-pavola, Chemical Constituents: dhotara. Sanskrit: Brahmadandi, Pitopushpa, The seed oil contains myristic, palmitic, Srigalkanta, Svarnakshiri. oleic, linoleic acids etc. The yellow juice Malyalam: Ponnummattu, Kantankattiri Tamil: Kutiyotti, Ponnummuttai containing small quantities of berberine, Telugu: Brahmadandicettu potassium nitrate was identified among the English name: Mexican prickly poppy salts naturally existing in the plant.

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Two aliphatic compounds; mexicanol and is used to treat the problem caused by tape- mexicanic acid have been isolated from worm. leaves. Three isoquinoline alkaloids have Other uses: The plant is found suitable for been isolated as dihydropalmitine the reclamation of alkaline soils. Oil cake is hydroxide; berberine and protopine from the used as manure. Dried and powdered plants seeds. Oil contain up to 40% free glycerides are recommended as green manure as it of fatty acids. contain sufficient amount of Nitrogen, Phosphorus and Potassium. Biodiesel A. mexicana seeds contain 22 - 36% of pale production from A. mexicana seed oil using yellow non-edible oil, called argemone oil crystalline manganese carbonate has been or katkar oil, which contains the toxic demonstrated. Seed oil, popularly known as alkaloids sanguinarine and Satyanashi oil is used as an illuminant, dihydrosanguinarine. Four quaternary lubricant, in soap making, and for protection isoquinoline alkaloids, dehydrocorydalmine, from termites (5, 6). jatrorrhizine, columbamine, and Ayurvedic Formulations: Svarnakshiri oxyberberine, have been isolated from the churna and tail whole plant of Argemone Mexicana (3,4). PHARMACOLOGICAL ACTIVITIES Traditional Uses: Neuropharmacological study According to Ayurveda the plant is diuretic, In the present study methanolic and ethyl purgative and destroys worms. It cures acetate extracts of Argemone mexicana lepsory, skin-diseases, inflammations and whole plant (Papaveraceae) were tested bilious fevers. Roots are anthelmintic. Juice orally in swiss albino mice at doses of 100 is used to cure ophthalmia and opacity of mg/kg, 200 mg/kg and 400 mg/kg b.w. for cornea. Seeds are purgative and sedative. CNS related activities. Papaveraceae family Seeds resemble mustard seeds and in India it is known to have CNS depressant activity, is used to adulterate mustard seed. Seed so A. mexicana was evaluated for CNS yield non edible toxic oil and causes lethal activities(7,8). Significant central and dropsy when used with mustard oil for peripheral nociceptive activity was observed cooking. In Homoeopathic system of for both extracts. Methanolic and ethyl medicine, the drug prepared from this herb acetate extract have also showed significant decrease in motor activity and fall off time

Journal of Medical Pharmaceutical and Allied Sciences (Vol-3_2014) 06; 20-28 22 of animals on rotating rod, along with Argemone mexicana Linn. in pain and sedative effect by potentiating febrile disorders in the south werstern area phenobarbitone-induced sleeping time. In of Burkina Fas(11). the acute toxicity study, both extracts was Toxicity of argemone mexicana seed, seed found to be safe upto 2500 mg/kg b.w. oil and their extracts These results suggested that methanolic and Albino rats received A. mexicana seed, seed ethyl acetate extracts of Argemone mexicana oil and ethanolic seed extracts in different show analgesic, anxiolytic and sedative dosages and routes of administration effects(9,10). suffered hyperae-sthesia, inappetence,

Antipyretic Activity intermittent diarrhea, emaciation and Leaves of Argemone mexicana L. decrease in body weight. Hepatorenal (Papaveraceae) are used in the folk medicine lesions accompanied with increase in serum of Burkina Faso (West Africa) to treat a GOT activity and urea concentration were variety of illness. The aqueous decoction is the pathological findings in rats (12). indicated in the treatment of malaria fever, Wound healing activity abdominal pains, and jaundice. A The petroleum ether, chloroform, methanol preliminary study led by the authors showed and aqueous extracts of the leaves of a good anti-hepatotoxic activity of leaves Argemone mexicana Linn. (Family: extracts against CCl4-induced hepatic injury Papaveraceae) were evaluated for their in Wistar rats. The present survey projects to wound healing activity in ratsusing excision determine the antipyretic activity of a (normal and infected), incision and dead lyophilized water decoction (of Argemone space wound models respectively. The mexicana powdered leaf). The plant extract effects of test samples on the rate of wound was tested at 250 and 500 mg/kg p.o. for its healing were assessed by the rate of wound antipyretic potential by using yeast induced closure, period of epithelialisation, wound pyrexia method in mice. Both the breaking strength, weights of the granulation lyophilized extract (aqueous decoction) was tissue,determination of hydroxyproline, found to exhibit significant (p<0,05) dose- super oxide dismutase (SOD), catalase and dependent antipyretic activity in tested histopathology of the granulation tissues. model when compared to control group. Nitrofurazone (0.2% w/w) in Simple These results support the traditional use of ointment I. P. was used as reference

Journal of Medical Pharmaceutical and Allied Sciences (Vol-3_2014) 06; 20-28 23 standard for the activity comparison. The edema method. It was found that lyophilized results of the study revealed that the animals extract can be effective in treated with methanol and aqueous extracts acuteinflammatory disorders and in that of A. mexicana showed faster rate of wound case, it showed significant anti- healing compared to other extracts under inflammatory dose-dependent study. The chloroform extract of the selected effect(p<0,001) at the dose level of 250 plants also produced promising results but mg/kg and 500 mg/kg.The plant extract was the effects are seen to be of lesser extent equally tested for its analgesic potential by than the corresponding methanol and using the hot plate test method and acetic aqueous extracts. The petroleum ether acid Writhing method. The lyophilized extract did not produce significant extract was found to exhibit significant results.The wound healing effects of the (p<0,01; p<0,001) analgesic activity in chloroform, methanol and aqueous extracts tested model. By the hot plate method, the may be attributed to the presence of drug extract showed significant (p<0,001) phytoconstituents like alkaloids, increased latency periodthan the control triterpenoids, tannins and flavonoids in the group at oral dose of 250 and 500 mg/kg.In extracts which are known to promote the acetic acid induced writhing test, the wound healing process mainly due to their lyophilized extract (250 & 500mg/kg) astringent, antioxidant and antimicrobial presented reduced number of writhes at the properties. The present work justifies the use two dose levels, which were found of the leaves of A. mexicana for wound significant (p<0,05; p<0,001) if compared to healing activity as claimed in the folklore control group.These results support the use literature (13). of Argemone mexicana Linn. for the Anti-inflammatory and analgesic treatment of pain and inflammation activities sickness(14)

The present study deals with evaluation of Anti-candida activity the anti-inflammatory and analgesic In-vivo anti-candidiasis efficacy of GE. The properties of a lyophilized leafextract of results indicate that GE exhibits inhibitory Argemone mexicana Linn. on laboratory effects against candidiasis in both control animal. The anti-inflammatory study was and diabetic rats. The anti-candidial effects done by usingcarrageenan-induced paw of garlic attributed mainly to allicin. Allicin,

Journal of Medical Pharmaceutical and Allied Sciences (Vol-3_2014) 06; 20-28 24 one of the active principles of freshly indicates that AGE has a broad spectrum crushed garlichomogenates, has a variety of (15). anti-bacterial, antifungal (particularly Inhibition of mild steel corrosion in against C. albicans), anti-parasitic and anti- sulfuric acid solutions viral activities. It has been reported that Inhibition potential of Argemone mexicana blockage of lipid synthesis, enhancement of leaf extract (AMLE) for corrosion inhibition phagocytosis and increase in natural killer of mild steel in 0.5 M H2SO4 has been cell activity may be important components determined by weight loss, Tafel of the anti-candidal activity of garlic. It has polarization and electrochemical impedance been reported that the use of fresh garlic is spectroscopy techniques. It is found from more effective for antimicrobial activity the results of weight loss method that than that from old garlic. These results inhibition efficiency of AMLE increases in indicate that GE exhibits inhibitory effects concentration dependent manner which is against candidiasis and therefore validates also supported by the results of the traditional use of the plant in fungal electrochemical techniques. Maximum infections in diabetic patients. A study on in inhibition efficiency of 87% has been vitro antimicrobial properties of aqueous GE achieved using 600 mg L-1 of inhibitor. against multidrug-resistant (MDR) bacteria Adsorption behavior of AMLE has been and Candida species from Nigeria reported studied and it is found to be described most that the anticandidal effect of aqueous garlic suitably by Langmuir isotherm. Organic extract (AGE) resulted in a growth moieties present in extract are found inhibition zone of 27.4 ± 3.7 mm with no responsible for effective performance of significant difference (P > .05) in MIC inhibitor which is well supported by optical values at 24 and 48 hours. MFC were found microscopy and FTIR studies (16).

to be 14.9 and 15.5 mg/mL, at these Antidiabetic activity incubation periods. The observed zone of Argemone mexicana L. (Papaveraceae) inhibition on agar of gram-positive and commonly known as prickly poppy is an gramnegative bacteria and Candida isolates indigenous herb used as a medicinal plant in were comparable to those elicited by several countries.The investigation was ciprofloxacin and FLU, showing that the carried out to study the effects of chloroform isolates exhibitedsusceptibility. This and aqueous soluble fractions from

Journal of Medical Pharmaceutical and Allied Sciences (Vol-3_2014) 06; 20-28 25 hydroalcoholic extract of Argemone potential anti-diabetic action of chloroform mexicana in normoglycemic and alloxan and aqueous fractions of A.Mexicana is induced diabetic rats. It was also intended to plausibly due to its modulation of establishcorrelation between the marker endogenous antioxidant status (19). antioxidant enzymes and diabetes(17,18). Bacteriostatic potential Hyperglycemia was induced in rats by Bacterostatic efficacy of 16 crude extracts alloxan monohydrate (150mg/kg body derived from different parts of Argemone weight i.p.). After alloxan induction diabetic Mexicana (Papaveraceae) has been analyzed rats received chloroform and aqueous on enteropathogenic bacteria such as fractions orally at 150 mg/kg body weight Klebsiella oxytoca, vibrio damsella, daily for 21days. The parameters studied Enterobacter aerogenes and Escherichia coli. were blood glucose, creatinine and urea, The bacteriostatic efficacy was elucidated serum lipid profile, serum enzymes (serum using single disc diffusion method. The glutamate pyruvate transaminases and serum minimum inhibitory concentration of the glutamate oxaloacetate transaminases, lipid extracts showing higher efficacy against the peroxidation, antioxidant enzymes (catalase test organism was determined. The MIC of (CAT), superoxide dismutase and reduced acetone extract of seed and aqueous extract glutathione. The results of test drug were of leaf on different bacteria tested were compared with standard hypoglycaemic found to be between 0.0005-0.02 mg/disc drug-glibenclamide (5 mg/kg). All data were (20). expressed as means ± SEM. Dunnet’s t-test Anti-malarial activity and one-way ANOVA test was used to A prospective, dose-escalating, quasi- compare the mean values of test groups and experimental clinical trial was conducted with control.Experimental findings showed that a traditional healer using a decoction of the chloroform and aqueous soluble Argemone mexicana for the treatment of fractions significantly (P < 0.01)normalized malaria. The remedy was prescribed in three blood glucose levels, serum biochemical regimens: once daily for 3 days to group A; twice daily for 7 days to group B; and four parameters; decreased LPO and recovered times daily for the first 4 days followed by glutathione-S-tranferase (GST) and CAT as twice daily for 3 days to group C. Thus, 80 compared with those of alloxan controls.. patients were included, of whom 80% were From this study it may be concluded that the aged <5 years and 25% were aged <1 year.

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All presented to the traditional healer with produced relaxation from contraction symptoms of malaria and had a Plasmodium induced by norepinephrine (NE: 1X10-7 M) falciparum parasitaemia >2000/μl but no signs in a concentration-dependent manner (0.1 at of severe malaria. The proportions of adequate 1000 μg/ml). At higher concentrations (310 clinical response (ACR) at Day 14 were 35%, and 1000 μg/ml), the extract induced 73% and 65% in Groups A, B and C, significant additional tension. When applied respectively (P = 0.011). At Day 14, overall to relaxed aortic tissue, addition of the proportions of ACR were lower in children extract produced concentration dependent aged <1 year (45%) and higher in patients contraction. Vasoconstrictor and aged >5 years (81%) (P = 0.027). Very few vasorelaxant effects produced by the extract, patients had complete parasite clearance, but were not altered significantly in at Day 14, 67% of patients with ACR had a endothelium-denuded rings, however, parasitaemia <2000/μ (21). phenoxi- benzamine (1 mg/ml) produced a Antiplasmodial activity rightward shift in the concentration– By the research 20 species, with low IC50 contractile response curve to the extract. On values of 9–43 mg dry extract / ml have the other hand, the extract relaxed been shown to possess antiplasmodial significantly the contraction induced by KCl activity in all of them, Argemone mexicana (40 mM). The results indicate that the L. (Papavaraceae) also shown the same extract induces a direct dual specific effect activity which is vary by varying extract upon the vascular smooth muscle, mediated, dose per kg/ body wt. concentration: In vitro at least in part, by adrenergic receptors. The inhibition (%) of plant extracts against petroleum ether, CHCl3, CHCl3/MeOH chloroquine susceptible strain of P. (9:1), MeOH extract and partially purified falciparum. The result shows: Mg dry fractions and pure compounds from extract / 80 mg part dry plant material 2.50, Argemone mexicana examined on the % Inhibition (mg:ml) according to dose i.e. electrically induced contractions of the 100 μg/ml ; 50 μg/ml ; 25 μg /ml; 12.5 μg isolated guinea-pig ileum (E.C.I.). The /ml ; and IC50 μg /m(21). results of the experiments indicate that Vasorelaxant activity CHCl3/MeOH (9:1) and MeOH extracts, The vascular effects of a methanolic extract tested at a concentration of 400, 200 and 100 of the aerial part Argemone mexicana was mg/mL, dose-dependently reduced the investigated in rat aortic rings. The extract

Journal of Medical Pharmaceutical and Allied Sciences (Vol-3_2014) 06; 20-28 27 guinea-pig ileum contractions, whereas the antistress potential in asthma by milk- petroleum ether and CHCl3 extracts did not induced leucocytosis and milk-induced affect it. Furthermore, the partially purified eosinophilia. Aqueous extracts showed fractions II-V from the MeOH extract, each significant (P<0.05) decrease in leucocytes tested at concentrations of 200, 100 and 50 and eosinophils, methanol extract also mg/mL also inhibited E.C.I. Finally the pure showed comparable results with aqueous compounds 1-2 (5×10-6-1×10-5-5×10-5 M) extract while petroleum ether and acetone isolated and purified from the above extracts were inactive. This shows polar fractions significantly reduced, in a dose constituents of A. mexicana stem are dependent manner, the electrical responsible for antistress and antiallergic contractions of the ileum, whereas activity(21). compound 3 (5×10-6-1×10-5×10-5 M) increased them. Since the active compounds Milk-induced leucocytosis 1-3 were respectively identified as Amongst mice pretreated with various protopine, allocryptopine and berberine by extracts of A. mexicana stem, aqueous and NMR, the observed effects could be related methanol extracts showed significant mainly to these compounds(21). reduction in leucocytes, induced by Antiasthmatic activity milk(21). The research title i.e. Medicinal plants used Milk-induced eosinophilia to treat asthma in Andhra Pradesh, India Amongst mice pretreated with various proved that Argemone mexicana L. extracts of A. mexicana stem, aqueous and (Papaveraceae) (common or local name: methanol extracts showed significant Brahmadand) Seed powder, 100–200 mg reduction in eosinophil count(21). taken twice a day, for 2 weeks shows Anti-HIV activity significant effect on asthama as The alkaloids isolated from methanolic antiasthamatic activity 24. Anti-Stress and extract of the Argemone mexicana were Antiallergic Effect of Argemone mexicana evaluated for anti-HIV activity. In which Stems in Asthma shows: Petroleum ether, benzo(c)phenanthridine (+/-)-6- acetone and methanol and aqueous extracts acetonyldihydro chelerythrine exhibited of Argemone mexicana stem (50 mg/kg, i.p.) significant anti-HIV activity in H9 was screened for its antiallergic and lymphocytes with EC50 and TI (Therapeutic

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Index) values of 1.77 μ /ml and 14.6, Curvularia sp. All the five fungi were respectively (21). significantly inhibited at 1 000 to 5 000 ppm Opoid withdrawal concentrations(22). The MeOH extract, partially purified TOXICITY AND SAFETY fraction (IV), and pure compounds from EVALUATION The plants is toxic to animals and cattle Argemone mexicana examined for its effect avoid grazing this plant. Harmful on the morphine withdrawal in guinea pig allelopathic effects of Argemone mexicana isolated ileum. The MeOH extract, the on germination and seedling vigour of partially purified fraction (IV), and the pure wheat, mustard, fenugreek, sorghum, compounds isolated from A. mexicana fingermillet, tomato, cucumber etc. significantly and in a concentration- (important crops in India) have been dependent manner reduced the morphine reported. The allelochemicals cinnamic and withdrawal. Since the pure compounds were benzoic acid are identified as harmful identified as protopine and allocryptopine, chemicals responsible for inhibition of the observed effects could be related to these germination and seedling vigor.The alkaloid compounds. The results of the present study sanguinarine isolated from seeds of suggest that isoquinoline alkaloids may be Argemone mexicana was examined for its potential agents in the treatment of drug hepatotoxic potential in rats. The studies abuse(21). showed that a single i.p. dose (10 mg/kg) of Fungal spore germination inhibition sanguinarine not only increased the activity The alkaloids dehydrocorydalmine and of SGPT and SGOT substantially but also oxyberberine isolated from Argemone caused a significant loss of microsomal mexicana were assessed against spore cytochrome P-450 and benzphetamine N- germination of some fungi, e.g., Alternaria methylase activity. Furthermore, the treated cajani, Bipolaris sp.,Helminthosporium sp., rats exhibited considerable loss of body and Fusarium udum and Curvularia sp. While liver weight, peritoneal edema and slightly dehydrocorydalmineinhibited 100% spore enlarged livers with fibrinous material. germination of the fungi Helminthosporium Microscopic examination of the liver tissue sp. And Curvularia sp. at 5 000 ppm, showed progressive cellular degeneration oxyberberine showed similar activity against and necrosis further substantiating that spore germination of Bipolaris sp. and sanguinarine is a potential hepatotoxic

Journal of Medical Pharmaceutical and Allied Sciences (Vol-3_2014) 06; 20-28 29 alkaloid 31. Toxicolethal effects of seeds of 90 days in rats: Epidemic dropsy is a disease Argemone mexicana were investigated in to caused by the consumption of mustard oil roof rat, (Rattus rattus L). The argemone contaminated with argemone oil (AO). seeds were fed at 100% of the diet up to the During 1998 dropsy in New Delhi, which is death or for a maximum of 10 days. so far the largest with more than 3000 Observed signs of poisoning were sedation, victims and over 60 deaths, it was enquired passiveness, sluggishness, feeble or no at various scientific and regulatory meetings muscular jerks, abdominal contractions and about the maximum tolerated dose of AO. increased defecation. Also black secretions Animals were given AO in diet at a dose of from the eyes, corneal opacity, erection of 0.001%, 0.01%, 0.1%, 0.5% and 1% daily hairs, and edema of the hind legs and for 90 days and the two control groups submandibular space in were noted. received the standard diet with and without Fourteen of 16 rats died. Significant 1% mustard oil. A decrease in body weight reduction in the weights of the rats was gain (28–31%) was observed in 0.5% and observed. There were significant increases 1% AO groups; while significant increases in blood glucose, BUN and SGOT. Major in relative lungs and liver weight was histopathological lesions were: noticed in respective doses of 0.01% and hepatocytolysis, nuclear degeneration, 0.1% AO groups as well as in higher dosage pyknosis, cloudy swelling and dilatated animals. Reduction in RBC count and sinusoids disturbing the lobulalar haemoglobin content (p < 0.05) was noticed architecture of the liver; proliferated in 0.01% and 0.1% AO exposed animals. endothelium of glomeruli, hemorrhage in This effect was more pronounced in higher glomeruli and interstitium, and cloudy AO doses. Serum marker enzymes including swelling of convoluted tubular epithelium in alanine transaminase (ALT), aspartate the kidney cortical region; erosion and transaminase (AST), lactate dehydrogenase atrophy of the upper stomach mucosa and (LDH) and alkaline phosphatase (ALP) were calcification in the cardiac stomach, and; found to be significantly elevated in 0.01– erosion and congestion of the upper mucosa 1% AO groups. Further, a decrease in of the duodenum. No change was noticed in albumin/globulin ratio (42–78%) was the ileum 32. Safety evaluation studies on observed in the serum of 0.01% to higher argemone oil through dietary exposure for AO dose groups. The levels of serum

Journal of Medical Pharmaceutical and Allied Sciences (Vol-3_2014) 06; 20-28 30 triglycerides and VLDL cholesterol were sanguinarine alkaloid is the major found to be enhanced (p < 0.05) in AO component of argemone oil, the in vivo treated (0.01–1.0%) animals. DNA damaging potential of the isolated Histopathological changes in lung were alkaloid was investigated in blood and bone observed at 0.01% dose of AO while liver, marrow cells of mice using alkaline Comet kidney and heart produced produced assay. Swiss albino male mice were given changes at 0.1% AO and above doses. None single intraperitoneal administration of 1.35, of the parameters were found to be affected 2.70, 5.40, 10.80 and 21.60 mg sanguinarine in 0.001% AO treated animals. These results alkaloid/kg bwt., while controls were treated suggest that the no observed adverse effect with saline in the same manner. The results level (NOAEL) dose of AO is 0.001% in revealed a dose dependent increase in DNA rats and considering a factor of 100 for damage in blood and bone marrow cells humans for highly toxic compound, the safe following 24h treatment of sanguinarine limit of 0.00001% (100 ppb or 100 ng AO/g alkaloid. All the three parameters of Comet oil) AO can be implicated which shall assay including olive tail moment (OTM), contain only 0.55% of sanguinarine tail length and tail DNA showed significant equivalent to 0.6 ng sanguinarine per gram (p < 0.05) increases in blood and bone oil. However, the minimum detectable limit marrow cells at respective doses of 10.80 of AO is 5 ppm (equivalent to 5 ng and 5.40 mg alkaloid/kg bwt. However, sanguinarine per gram oil) with the present some of the parameters were significantly existing HPLC method, thereby suggesting increased even at lower doses of that mustard oil should be absolutely free sanguinarine alkaloid (2.70 mg/kg bwt.). from AO contamination 33. In vivo DNA The frequency of cells exhibiting greater damaging potential of sanguinarine alkaloid, DNA damage was found to be increased by isolated from argemone oil, using alkaline sanguinarine alkaloid in a concentration Comet assay in mice: Consumption of dependent manner. These results indicate mustard oil contaminated with argemone oil that single exposure of sanguinarine alkaloid is well known to cause clinical manifestation causes DNA damage in blood and bone referred to as ‘‘Epidemic Dropsy’’. Our marrow cells of mice, which could be prior studies have shown that argemone oil responsible for the genotoxicity of argemone produces genotoxic effects in mice30Since, oil. The present study clearly indicates that

Journal of Medical Pharmaceutical and Allied Sciences (Vol-3_2014) 06; 20-28 31 sanguinarine alkaloid, an active ingredient metabolic activation system. However, it of argemone oil possesses DNA damaging raised the possibility of usage of Sanguinaria potential in blood and bone marrow cells extract in toothpaste in the development of using alkaline Comet assay. These results oral leukoplakia (23-26). fully support the earlier observation that in CONCLUSION vivo argemone oil caused genotoxicity by The extensive survey literature reviewed enhancing the frequencies of chromosomal that Argemone mexicana Linn, has some aberrations, micronuclei formation and important medicinal activity but also cause development of Comets resulting in DNA considerable toxicity. Further evaluation damage 30. In this regard studies have need to be carried out on Argemone shown that sanguinarine forms DNA mexicana in order to explore concealed adducts following metabolism by areas and their practical clinical application, cytochrome P-450 system under in vitro which can be used for the welfare of the conditions 34. It has been suggested that mankind. There is a scope to identify new sanguinarine may undergo N-demethylation compound and check claimed by cytochrome P-450.32 Since, sanguinarine pharmacological activity by eliminating has been shown to cause inactivation of toxic effect. And identify new mean for cytochrome P-450, it can be argued that the elimination of toxic effect to get toxic free N-demethylated product of sanguinarine or as well as significant response on claimed any other electrophilic metabolite, could be pharmacological activity. responsible for this effect. The decrease in cytochrome P-450 thereby impairs the REFERENCES elimination of a metabolite of sanguinarine, 1. Saurabh RV, Nagori BP, Singh GK, identified as benzacridine, in urine and Dubey BK, 2012. A review on feces. Although, minimum group of Argemone mexicana linn.- An Indian sanguinarine has been shown to have medicinal plant. IJPSR, 8, 2494- affinity with b-form duplex DNA by 2501. intercalation with a high preference to G–C 2. Fuller Thomas C, 1986. Poisonous base pairs nonetheless, it could not reveal plants of California. University of genotoxicity in SOS chromtest using E. coli California Press. pp. 201-208. PQ37 in the absence and presence of

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