Argentinean’s Plants with Interest in Ethnomedicine as Wormers

Plants are different all over the world and its indications change according to the country they are located. This paper is developed in order to perform a comprehensive literature ́s review about plants used as anti-parasitic either in traditional or popular medicine in Argentina, and to provide a scientific support for their use in this medical indication. All Ethnobotany, Ethnomedicine, Phytomedicine books from Libraries of the Faculty of Exact Sciences Faculty of Medical Sciences, Agricultural Science, from all National Universities in Argentina were included in the study. Herbal characteristics and therapies were searched in online databases such as Medline PubMed, Science Direct and Scopus. The results obtained show the potential of Ethnomedicine in Argentina as a source of active ingredients for phytotherapy, providing data about species for antiparasitic treatment. Thus, we found many Argentinean’s plants with anti-parasitic properties which might be considered alternatives for natural treatment or future drug development against wormers.


Introduction
Traditionally plants coming from each geographic region of the world had been used for medical purposes for several centuries. This knowledge has been maintained through oral transmission from generation to generation [1].
But this information is rapidly disappearing due to the adoption of measures from new modern culture that displaced the traditional wisdom.
The importance of documenting this knowledge derived from technological changes, or people's socio-economic features, which led to a disuse or total loss of traditional knowledge [2]. Noteworthy, this interest in herbal medicine has increased in the last years.
Pharmaceutical companies focus their attention in the research of new molecules, since classical treatments usually develop resistance. This is the case of anti-parasitic drugs. The last decades were marked by a progressive increase in drug resistance and in rising of the costs of therapies. The research and development of new knowledge about herbs is not longer an option but a necessity. International Journal of Pharmacology, Phytochemistry and Ethnomedicine Vol. 5 3 Figure 1. Species according to their families Table 2 shows a complete data about authors who support its antiparasitic use. It is also been detailed, the part of the plant used, its official use, if the herbs are classified as toxic, and their active ingredients and their possible dosage.
Although the plants are now growing in the Argentine territory, it was explored the original source of them, and this data is shown in figure 2.

The sources used:
We have observed an extensive use of plants that have European origins, maybe based in the fact that Argentine population has their roots predominantly in European countries like Italy and Spain. Mediterranean area of these countries has similar climate, temperature and humidity than vast areas of Argentina (figure 2).
The main part used from plants were leaves, stems, whole plant, seeds, aerial parts, flowering tops, fruits, root, oil or juice (Table 2, Figure 3).

Analysis of the most significant plants
The bulb of Allium sativum L. known as the "Garlic" belonging to the family of a liliáceaes shown to have activity against different parasites [7] intestinal parasites (oxyuriasis) [8][9][10], or intestinal worms [11]. Its effectiveness is due to the presence of the allylic and acid allicin, which would confer the amebicide and anthelmintic properties.
Ajoene is effective against T. cruzi epimastigotes and amastigotes. With such trypanocidal activity, garlic derivates could be used as an alternative treatment for African-trypanosomiasis, considering that current drugs for brain infections (sleeping sickness) are extremely toxic.
The mechanism of action of the allicin and ajoene is through its interaction with thiol groups present on enzymes, inhibiting cysteine proteases, alcohol dehydrogenases and thioredoxin reductases of parasites like E. histolytica. Ajoene in the T. cruzi inhibits proliferation, possibly by inhibiting the biosynthesis of phosphatidylcholine, by interfering with traffic of ºproteins and lipids in the cell membranes of the parasite. Ajoene inhibits the final stage of the biosynthesis of phosphatidylcholine and modifies of the composition of the cell membrane phospholipids [13]. Many polyphenols (hydrolysable tannins, proanthocyanidins, caffeic acid products) demonstrated to reduce intracellular survival form of Leishmania donovani amastigotes in vitro. The effects of polyphenols against intracellular parasites of Leishmania are due to the activation of macrophages rather antiparasitic activity [9,14,15].
Within the genus Artemisia, belonging to the family of asteraceaes we identified 5 species with antiparasitic properties including the popularly known since ancient times Artemisia absintium. But it is noteworthy that the similarity between them allows the use of one specie instead of the other.
The leaves and flowering tops of Artemisia absintium commonly known as "Wormwood" in the family of asteraceaes possess a demonstrated antimalarian effect in countless articles. It has Beta-thujone, which gives it a pesticide and insect repellent effect. The sequiterpene lactones, would serve to combat intestinal parasites, but their use is limited because its toxicity. It has been used for centuries as an anthelmintic, especially against roundworms and earthworms [11]. Since the essential oil is volatile, and absintine contains thujone, the product is extremely powerful, so, even at very low doses, it may cause coma or death in adults. For this reason, it is preferred to use dried plant material instead of essential oil [12,16]. It should be keep in mind that in the Pharmacopoeia Argentina VIII edition, this plant drug is classified by its toxic properties.
Popularly, wormwood tincture of Artemisia is used for other purposes, such as hallucinogen. Artemisia contains santonin which has a selective toxic action on the node located in the nerve ring of Ascaris spp. However, it narrow range of activity does not include Oxyuris spp. or tapeworms [11,17].
It is published that the aerial parts of this family of plants are effective against nematodes and worms (20-30 g aerial parts in 500 ml of boiling water for 20 minutes, cool, strain and take 15ml / kg body weight). The sweet wormwood (Artemisia annua) has less negative components of A. absinthium [12].
On the other hand, the infusion of the leaves and stems has proven its action against amoeba (Entamoeba histolytica) (2 g / L, children and adults, 10 g / L. In all cases take 300 to 400 mL per day in 3 divided doses). It should be noted that the essential oil contains highly toxic substances foliage, so, not controlled use can cause vomiting, dizziness, seizures, hallucinations, disorders of sensation and other severe diseases of the CNS if doses are exceeded [18].
Annua, used in the Río de la Plata because its antiparasitic properties, is active in wild wormwood. [12,19]. It is also used in Chinese medicine for its proven activity as antimalaric against Plasmodium falciparum [20].

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Volume 5 The leaves, flowering tops and essence of Artemisia abrotamum L. popularly known as "Abrotane male", is given a high level of effectiveness and its use as an anthelmintic [6,7,12].
Infusions of leaves and flowering tops of Artemisia mendozana are well known because of its vermifuge properties against wormwood for intestinal parasitism treatment [21].
Literature also mentions its use by Mapuche's communities of NW Patagonia. The flowering tops of Artemisia maritima L popularly known as "Wormwood Maritime" has been shown to be active against threadworm and ascaris but its toxicity is similar to castor oil [7] and can produce visual disturbances as side effects.
The oil obtained by distillation of whole plant of A. herba albay vulgaris popularly known as "Artemis", is an essential oil that contains plenty different terpenes and terpene derivatives (1.8 cineol, camphor, linalool, tujone, 4-terpineol, borneol, a-Cardinol), artemisia ketone, flavonoids, poliínos, numerous coumarins and sesquiterpene lactones (artemisinin artemisinic acid arteanuina B, etc.). It was used as an anthelmintic, but has fallen into disuse because of its toxicity, adverse reactions such as allergies and abortive activity [20].
Its use as an antimalarial in cases of severe falciparum malaria in situation of resistance to other antimalarials [22].
In conclusion, Artemis has a very old reputation as an anthelmintic [23]. All Artemis species contain thuyona Artemisia essential oil which is somewhat toxic. Because of this, these plants should not been used in high doses, since it can cause dizziness, headache, convulsions, hallucinations, addiction, tremors, nausea and vomiting [21].
The Asclepia popularly known as "Spanish Banderita or Spanish Flag" belongs to the family of Asclepiadáceaes. The whole plant is considered toxic (Ed. FA VIII) and its milky juice is caustic. However it is recorded in ethnomedicine that this specie has anti-parasitic (with leaf infusion), insecticidal and anthelmintic actions (diluted latex). In Aldama, México few drops of milky juice in 500ml of water are consume throughout the day [24] as anthelmintic and also for cardiac stimulation -since it has glucoside action- [25,26].
The root Atractylis gummifera L popularly known as "League" in the family of Asteraceaes is classified as toxic plant drug (FA VIII Ed.) but records shows that mixed with food acts as a repellent and insecticide for bug and external parasites. The mechanism of action is explained because the composition contains atractyloside (ATR) and carboxiatractiloside, two diterpene heterosides that cause inhibition of the respiratory chain at the cellular level (C Hamouda, 2004). The toxic effect arises from ATR, a potent inhibitor of oxidative phosphorylation in mitochondria [27].
The essence oil Castile erecta ssp popularly known as "Bizbirinda", "bitter squat" belonging to the family of Lorantáceaes destroys parasites in adulthood and its cyst form in the intestinal mucosa [28].
The leaves and fruit of Chenopodium ambrosioides L. popularly known as "Goosefoot", "Piako", "paico", belonging to the family of Amaranthaceaes, is considered vermifuge since the oil obtained from the whole plant is toxic for parasites (FA VIII Ed.) Chenopodium oil is known as an effective anthelmintic due to its contents of ascaridol. Although it is widely used, however, the application is not easy since it must be followed by a treatment with a laxative, immediately after ingestion.
Infusion and decoction for internal is used as an external antiparasitic and anthelmintic and it is also use in topical applications as antiparasitic and scabicide. Dry powder and seeds are used against parasites, hookworms and tapeworms, and on the floor like flea [28].
In a rural community in Huaraz, Peru, a clinical essay with 60 children, aged 3 to 14 years old, was performed dividing these patients in a randomized way into two groups of treatment Albendazole and Paico (n = 30 each group). All the patients were initially evaluated as positively for Áscaris lumbricoides in stool. Treatment consisted of Paico juice: 1 ml / kg for children less than 10 kg, 2 ml / kg dose for 3 consecutive days. Administration of Albendazole was a done by a single dose of 400 mg in children over 5 years and 200 mg in young adults. The main objective International Journal of Pharmacology, Phytochemistry and Ethnomedicine Vol. 5 parameter was the complete disappearance of Ascaris eggs and additional quantitative parameter was reduced parasite load. The research was performed in the laboratory of the Regional Health Directorate of Ancash. Eradication rates for Ascaris with Albendazole or Paico were both about 86%. Quantitative effectiveness was 59.5% and 58.3% for Paico and Albendazole respectively. The authors conclude that Paico have similar efficacy that Albendazole against Ascaris lumbricoides. Paico also had the added benefit of being effective against Hymenolepis nana [29].
Another study of leaf extracts in two villages near Tarapoto, San Martin, Peru included 72 patients with intestinal parasitic infections. Status was examined before and after 8 days after ingestion, confirming 100% of the efficacy against Ancylostoma and Trichuris and 50% against Ascaris. There were no significant differences in age or sex [30].
The root bark and trunk of Cinchona spp, popularly known as "Quina" belonging to the family of Rubiaceaes, has antimalarial activity, since it is rich in phenolic compounds including you cinconaines; proantocianidoles, quinic acid, saponins, alpha-terpineol, linalool, limonene , terpenes [31,32]. Anti-malarial activity of quinine was demonstrated either for treatment and prophylaxis of Plasmodium vivax malarias, P. falciparum, P. ovale and P. malarie and inactivation of sporozoites and tissue forms [23].
Seeds of Cucurbita popularly known as "Pumpkin" belonging to the family of Cucurbitáceae is active against Taenia spp, Hymenolepis spp, Enterobius spp, Ascaris spp, [11,18,21]. This action is due to the cucurbitine which is active in trematodes, but inactive against nematodes and cestodos. The advantage this family is that it has no hepatic and gastrointestinal toxicity [32]. Formulation could be prepare as follows: 60 g of crushed seeds, 40 g of sugar, 60 mL of water, boiled for 20 min, mixing and emulsifying unstrained. Patients should take 1 portion daily [18].
The seeds of Delphinium staphisagria L. popularly known as "Estafisgria", or "Kill lice", belonging to the family of Ranunculaceaes, demonstrated antiparasitic action, specially active against pediculosis, scabies and Chagas disease [7,34]. Since it contains (toxic) alkaloids, it is recommend to use is as external plant powder as environment repellent.
From dried flower of Eugenia caryophyllus popularly known as "Nail" belonging to the family of Myrtaceaes, it can be obtained an essential oil that showed acaricidal activity against Dermatophagoides farinae and D. pteronyssinus eugenol, Psoroptes cuniculi. Dried flowers ground cloves (Eugenia caryophyllus) are also prepared as a tea infusion with 4 g of powdered herb per 250 ml of boiling water. This should be soaked for 10-20 min, cooled and strained. The dose used was 15 ml per day per 11 kg of body weight for 2-3 days. Oil from this plant is not considered safe for pets [12]. Eugenia caryophyllus may contribute to parasitide action either alone or in combination. Alpha-thujone, the active ingredient of wormwood oil, was reported with insecticide and antihelmintic activity [35]. The eugenol and caryophyllene in Eugenia caryophyllata are also informed as anti-helmintic compounds [36,37,38].
The whole plant of Eugenia uniflora popularly known as "ñangapiry pitanga " belongs to the family of Myrtaceaes, and is found in the tropical jungles of Argentina, Brazil, Paraguay, southern Mexico and Paraguay. It is used in the Guarani communities for their antihelmintic properties [39,40,41]. The plant contains licopene composition, terpene compounds, oxalic acid, chlorogenic acid, pitagina, cineol, beta carotenesand citric acid [41,42].
The root of Inula helenium L. rhizome popularly known as "Elecampane, grass moro" belongs to the family of Asteraceaes and has an intestinal antiparasitic properties. Sequiterpenos found in its composition, triterpene alcohols, inulin, helenina, azulene, sterols, fructans and mucilages, essential oil (Enula camphor) [7,43] are the basis of its vermifuge action. Decoction of the roots and

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Volume 5 rhizomes, ointment extracts, powdered drug and essential oil obtained by distillation are all formulations used in traditional medicine. The dried leaves of Juglans regia popularly known as "Walnut" belonging to the family of Asteraceaes, originally from Persia and cultivated in North-West of Argentina have demonstrated anthelmintic activity against Haemonchus contortus in goats. Juglone, and naphthoquinone are the compounds of this family reported with anthelmintic activity [7,11,12,32]. It exist research data demonstrating that decoction and crushing and soaking water of this plant is useful as insect repellent [21].
The flowering tops Matricaria chamomilla popularly known as "Manzanilla" belongs to the family of Asteraceaes. In infusion the plant only released 10 to 15% of the total content of essential oils. This oil is mainly composed of sesquiterpenes (azulene), and bisaboloides (camazulenbisabolol). On the other hand, water-soluble portion contains flavonoiglicosides, terpene, pectins and various oligosaccharides compounds.
It is considered as FA official drug, but its indication does not refer to the antiparasitic property, however, in Argentina it is use as an anti-helmintic agent. Some authors refer their activity mainly due to its flavonoids (apigenin and luteolin). [32,40].
The essential oil obtained from the leaves and dried flowering tops of Mentha piperita popularly known as "Mint" belongs to the family of Lamiaceaes. It has the property to remove worms and other parasites from the digestive tract, hence the Spanish proverb "jury is mint, never lie to the stomach" is based in this herb's action. Also is used for environmental repellent in ways bunches. The leaves contain essential oil (menthol, menthone, methyl acetate, mentafurane, isomenthone, pulegone, piperitone, cineol, limonene), flavonoids (apigenol, luteol, rutoside, mentosido), phenolic acids (caffeic, chlorogenic, rosmarinic), tannins and triterpenes (ursolic acid, oleanilic acid) [12,32]. Mentha cordifolia contains beta-sitosterol glycosides and has been tested against Ascaris suum showing a similar synthetic anthelmintic mebendazole on contact with the preparations of the parasite activity. Mint spp., has also been tested with succeed against Haemonchus contortus in ruminant hosts [12].
Balsamum Myroxylon popularly known as "Balm of Peru" belonging to the family Fabaceae is considered by Drugs Official USP as parasiticide and anthelmintic drug. Its resin is used to mange, lice, mites [7].
The root of Nephrodium popularly known as "male fern" belonging to the family of Polypodiaceae, is used for treatment against tapeworm. It is suggested to take either 1 capsule or drink an extract every 10 minute one hour after taking a saline purgative. It is not recommended in children, elderly, or patients suffering from kidney's disease [11].
Leaves of Nicotiana glauca Graham popularly known as "Palán-Palán" belonging to the family Solanaceae, is well known for its toxicity property due to anabasine, an alkaloid used for nicotine addiction treatment. It also contains pireridine, nicotine, nornicotine, citric, succinic, malic and oxalic acid. The family is considered an active ectoparasiticidal and anthelmintic [42,44,45]. The dried leaves of Nicotiana tabacum "snuff" belonging to the family Solanaceae, is considered toxic (Ed. FA VIII) and only is permitted for external use. It is used as ectoparasiticide in the form of nicotine salicylate (eudermol) or sulfate. It has also demonstrated to be useful for helminthiasis [25,46], however its toxicity limits this last indication. The external use of this plant includes treatment for scabies [47] and leeches [12,48].
The leaves, twigs, rhizomes of Podophyllum peltatum L "podophyllum" belonging to the family of Berberidáceaes is allowed only for external use [7], however in Argentina it is also use an anthelmintic (anti-worm) [49] since resin contains lignans [podophyllotoxin picropodophyllin, peltatin alpha-, beta-peltatin] heterosides glucosidices. It is well recognized in pediatric medicine as drug useful in digestive disorders. Its conservation is difficult because it's essential oil content decreases by 1% per month.
The root bark and occasionally the trunk and the fruits of Punica granatum L known as "Granado" belonging to the family Lythraceae has demonstrate action against tenias (accompanied International Journal of Pharmacology, Phytochemistry and Ethnomedicine Vol. 5 by a purgative to induce expulsion of tapeworm) [11]. The decoction of the root bark is the best way to obtain useful formulations [7]. Its use was recommended for 15 centuries as an anthelmintic (especially as taenicide). It contains alkaloids (pelletierine, isopeletierina, pseudopeletierine, Nmetilpeletierina) hydrolysable tannins (3,6-hexahidrofenoilglucosa, granatinas A and B, punicafolina, punicacorteínas A, B and C, punigluconina, punicalin, punicalagin). The harmful effects due to the fraction absorbed in the intestine, have led to quit its use and its indication rest for veterinary use. [11]. The flowering tops, stems, leaves and flowers of Deruta graveolens when extract and distilled in pot stills to steam, is known as "Ruda" (belonging to the family of Rutaceae) which gives an essential oil that has a light attributed to ketone nonylmethyl anthelmintic effect. Its odor inhibits the fifth instar Rhodnius prolixus of triatomines. That is why it is classified with a medium level validity as an anthelmintic [12,50] and because of that is suggested to associate this herb with the paico and wormwood for intestinal worms [11].
Leaf infusion of young branches of Santolina chamaecyparissus popularly known as "stranded Abrotano" belonging to the family of Asteraceaes; is used to repel aphids [7]. However, it is also used as an anti-helmintic in order to eliminate intestinal parasites in children.
Tanacetum cinararifolium popularly known as "Pyrethrum" belonging to the family Asteraceae is use as insecticide [7,26] and to eliminate parasites of pets [32].
The flowering tops of Tanacetum vulgare popularly known as "tansy tansy" also belongs to the family of Asteraceaes and has anti-helmintic properties (oil), worming and threadworm (branches, flowers and seeds) [7,11,40]. Tanacetum vulgare is prohibited for free sale to the public, because of its toxicity. Its use is restricted to the manufacture of pharmaceutical specialties, master formulas, officinal preparations, homeopathic stocks and research studies.
Young branches of Thuja occidentalis L popularly known as "Yours" belonging to the family of Cupressaceaes has anthelmintic [7] and insecticide activity [35,52]. This property can refer to the contents of Alpha-thujone.
The oil obtained from the leaves and flowering tops of Thymus vulgaris L. popularly known as "Thyme" belonging to the family of Lamiaceae, contains thymol, phenol, cimol, l-alpha pinene, beta pinene, camphene, terpinene, geraniol and caryophyllene; and it is indicated for intestinal worms. However, it use is limited because its hepatic toxicity, albuminuria, hematuria, allergic reactions and seizures (due to high doses of thymol) [7,53].
Leaves and stems of Verbena officinalis L. popularly known as "Verbena" belonging to the family Verbenaceae, has poor information about worming activity except for Ascaris [54]. European Commission believes that the plant cannot be recommended in therapeutics use since none of its indications have been justified with clinical studies or trials are also its side effects and toxicity are still unknown [11].

Conclusions
There are many plants found along Argentine territory that are not yet been well studied. That's why this work becomes interest in order to validate them as a tool for wormers control based on scientific publications.
Herbs have been used for centuries against endoparasiticides. The regulatory agencies (FDA, ANMAT) regulated some of the plants presented in our research like Artemisia absinthium, black walnut nut, and wormwood as useful herbs with vermicide action.
Since synthetic drugs have usually undesirably impact on the biology of our ecosystems and have also a residual effect on humans that ends in overall resistance to pesticides; plants species should be considered as alternatives to conventional chemical drugs anti-parasitic treatment.