Plants of the Araceae family for malaria and related diseases : a review

In the current work we performed a review of the Araceae family species traditionally used to treat malaria and its symptoms. The aim is to reveal the large number of antimalarial Araceae species used worldwide and their great unexplored potential as sources of antimalarial natural products. The SciFinder Scholar, Scielo, PubMed, ScienceDirect and Google books search engines were consulted. Forty-three records of 36 species and 23 genera of Araceae used for malaria and symptoms treatment were found. The neotropical genera Philodendron Schott and Anthurium Schott were the best represented for the use in the treatment of malaria, fevers, liver problems and headaches. Leaves and tubers were the most used parts and decoction was the most common preparation method. The extracts of Araceae species inhibit the in vitro growth of the human malaria parasite, the Plasmodium falciparum Welch, and significant median inhibitory concentrations (IC50) for extracts of guaimbê-sulcado (Rhaphidophora decursiva (Roxb.) Schott), aninga (Montrichardia linifera (Arruda) Schott), Culcasia lancifolia N.E. Br. and forest anchomanes (Anchomanes difformis (Blume) Engl.) have been reported demonstrating the antimalarial and cytotoxicity potential of the extracts and sub-fractions. In the only report about the antimalarial components of this family, the neolignan polysyphorin and the benzoperoxide rhaphidecurperoxin presented strong in vitro inhibition of the D6 and W2 strains of Plasmodium falciparum (IC50 = 368-540 ng/mL). No live study about antimalarial activity in animal models Recebido para publicação em 16/04/2014 Aceito para publicação em 24/10/2014 10.1590/1983-084X/14_024 REVISÃO


ABSTRACT:
In the current work we performed a review of the Araceae family species traditionally used to treat malaria and its symptoms.The aim is to reveal the large number of antimalarial Araceae species used worldwide and their great unexplored potential as sources of antimalarial natural products.The SciFinder Scholar, Scielo, PubMed, ScienceDirect and Google books search engines were consulted.Forty-three records of 36 species and 23 genera of Araceae used for malaria and symptoms treatment were found.The neotropical genera Philodendron Schott and Anthurium Schott were the best represented for the use in the treatment of malaria, fevers, liver problems and headaches.Leaves and tubers were the most used parts and decoction was the most common preparation method.The extracts of Araceae species inhibit the in vitro growth of the human malaria parasite, the Plasmodium falciparum Welch, and significant median inhibitory concentrations (IC 50 ) for extracts of guaimbê-sulcado (Rhaphidophora decursiva (Roxb.)Schott), aninga (Montrichardia linifera (Arruda) Schott), Culcasia lancifolia N.E.Br. and forest anchomanes (Anchomanes difformis (Blume) Engl.) have been reported demonstrating the antimalarial and cytotoxicity potential of the extracts and sub-fractions.In the only report about the antimalarial components of this family, the neolignan polysyphorin and the benzoperoxide rhaphidecurperoxin presented strong in vitro inhibition of the D6 and W2 strains of Plasmodium falciparum (IC 50 = 368-540 ng/mL).No live study about antimalarial activity in animal models

INTRODUCTION
Malaria is caused by protozoans of the genus Plasmodium that are transmitted to humans by the bite of infected, female Anopheles mosquitos.Malaria symptoms include fevers, headaches, vomiting and chills that appear 10-15 days after infection (WHO, 2014).Despite advances in its control and prevention in the past decade, malaria continues to be one of the world´s major transmissible diseases.It is responsible for high mortality in tropical and sub-tropical regions of the planet (Muñoz et al., 2000;Adebayo & Krettli, 2011;Tsabang et al., 2011).Several factors contribute to the unacceptably high malaria morbidity and mortality rates.The major human malaria parasites Plasmodium falciparum Welch and P. vivax Grassi & Feletti are acquiring resistance to the most important drugs, the quinoline antimalarials and artemisinin derivatives.Also, many ecosystems favor the ready reproduction and propagation of malaria vectors: mosquitos of the genus Anopheles Meigen.
In tropical regions where malaria is endemic, alternative therapies based on traditionally used antimalarial plants are used (Milliken, 1997a;Willcox et al. 2004;Blair & Madrigal, 2005).New drugs introduced into the therapeutic arsenal are mostly derived from natural products (Newman & Cragg, 2012).Plants provide secondary metabolites that are useful for the treatment of protozoan diseases such as malaria (Pohlit et al., 2013), leishmaniasis, and African and American trypanosomiasis (Schmidt et al., 2012a;2012b).In fact, traditionally-used antimalarial plants are the origin of the alkaloid quinine (isolated from species of Cinchona ) and the sesquiterpene artemisinin (isolated from Artemisia annua L.) that gave rise last century to the synthetic quinoline antimalarials (chloroquine, etc.) and semi-synthetic artemisinin derivatives (sodium artesunate, etc.).These two classes are the basis of artemisinin-combined therapies (ACTs) now used worldwide.Plants also help combat malaria by providing mosquito repellent and insecticidal oils (citronella, neem, etc.), solvent extracts and isolated chemicals (chrysanthamic acid, nicotine, etc.) that have given rise to the pyrethroid, neonicotinoid and other insecticides and repellents (Pohlit et al., 2011a;2011b).
The Araceae is one of the most botanically diverse families within the monocotolydons.It is comprised of ca.105 genera and 3,300 species worldwide (Croat, 1983;Mayo et al., 1997;Croat, 1998;Ribeiro et al., 1999;Coelho, 2000;Vargas, 2002).The greatest diversity of its species is in tropical America (Croat, 1998).Brazil is among the countries having the largest variety of Araceae, numbering 30 genera and 700 species (Mayo et al.,1997).
Over 800 species of Araceae are of economic importance (ornamental, edible, medicinal).For example, about 10% of the world population consumes taro corms (rhizomes of Colocasia esculenta (L.) Schott), the most cultivated species of Araceae.It is a foodstuff and foodstock for animals (Pedralli, 2002).Most species of Araceae are ornamental plants the most important of which are from the genera Anthurium Schott, Philodendron Schott, Dieffenbachia Schott, Monstera Adams and Zantedeschia Spreng.(Pedralli, 2002).In the Amazon region, many species of Araceae are used for medicinal purposes, including the treatment of malaria and associated fevers and the most important species are from the genus Philodendron Schott (Milliken et al. 1997a(Milliken et al. , 1997b;;Kvist et al., 2006;López et al., 2006).Species of Araceae traditionally used for malaria, fevers, headaches and liver disorders are reviewed.Relevant literature that reveals the antimalarial potential of extracts and isolated compounds, including median inhibitory concentrations (IC 50 ) against Plasmodium falciparum, are also reviewed.

SURVEY METHODS
This survey was performed mainly on the specialized literature published from July, 2010 until January, 2014, the first record on this topic was in 1977.Searches were performed in the Scifinder Scholar, Scielo, PubMed, Science Direct databases.In general, searches were performed using the terms Araceae antimalarial plants, Araceae fever, Araceae malaria and Araceae medicinal plants and library book collections and documents were used at the following institutions: HUAZ Herbarium of the University of Amazonia (Colombia) and the National Institute for Amazon Research (Manaus, Brazil).The data were compiled and organized in an Excel (Microsoft) spreadsheet containing information on has been conducted on a species of Araceae.More bioguided chemical composition studies about the in vitro and also thein vivo antimalarial activity of the Araceae are needed in order to enhance the knowledge about the antimalarial potential of this family.
Keywords:Anthurium, Philodendron, Rhaphidophora decursiva, Plasmodium falciparum, antimalarial plant.species name, regions where the plant is used, preparation methods, parts of the plants used and where available, information on chemical composition and pharmacological properties.

Species of araceae used in the treatment of malaria
Forty-three bibliographic sources were found on plants used to treat malaria and symptoms of malaria in the Araceae family.These works describe 38 species in 22 genera (Table 1).Philodendron Schott was the most cited genus with seven uses registered by communities in South American countries, including Brazil, Colombia, Equador, Peru and French Guyana (Figure 1).Antimalarial plants of the Araceae family are also found in Central America, Africa, Western Europe, Asia and Southeast Asia.
Twenty-one species of Araceae are specifically used to treat malaria and many are from South America.Thus, the aerial part of folha cheirosa, yeuri cumare (Anthurium oxycarpum Poepp.) is used by the Tacana Amerindians of Bolivia (Deharo et al., 2001) and macerates and decoctions of cipo de tara or tracua (Philodendron cf.linnaei Kunth) are indicated by the Tirios Amerindians of Suriname (Lopéz et al., 2006).Also, taioba (Xanthosoma sagittifolium (L.) Schott) is a widely cultivated tuber that is a foodstuff and foodstock for animals (Aiyeloja & Bello, 2006) and is used as an antimalarial along the Manso River in Minas Gerais, Brazil (Reskalla, 2001).In northern Brazil, an antimalarial aerial root infusion of a species of Philodendron is prepared by the native Watorik Yanomami (Milliken 1997a).In Togo, Africa, whole plant decoctions of tonflo (Pistia stratiotes L.) are used as antimalarials (Kyei et al., 2012).

Araceae species for fevers, headaches and other symptoms of malaria
Several plants have uses both in the treatment of malaria and also in the the treatment of the symptoms of malaria.Thus, whole plant decoctions of P. stratiotes are used in Togo to treat fevers and malaria infections (Lahitte et al., 1998;Kyei et al., 2012).
Some species of Araceae are not used specifically to treat malaria, but are used to treat symptoms often associated with malaria such as fevers and headaches.So, the indigenous Wayãpi in French Guyana treat fevers with a decoction of Tapi`Ykũ (Philodendron linnaei Kunth) (Grenand et al., 1987).Similarly, the Tukano of southeast Colombia treat headaches by placing fresh inflorescences of madona lily (Spathiphyllum floribundum (Linden & André) N.E.Br.) on the sick person´s forehead (Croat, 1994).Culcasia lancifolia N.E.Br. has been used by traditional healers to treat headaches, fevers and vomiting (Lekana-Douki et al., 2011).

Traditional methods of preparation of remedies
Decoction was the method of preparation most cited for antimalarial remedies based on species of Araceae.Leaves and the tubercules were the parts most often cited.Few details on the method of preparation are included in many reports (Table 1).Some methods of preparation and treatments are, however, especially interesting.Three slices of hoa pouk, also called habarala (Alocasia macrorrhizos (L.) G. Don) are boiled with 3 pieces of sugar cane and 7 unpolished rice grains in the Province of Khammouane, Laos.A non-malarious person who drinks the decoction is said to become itchy wheras someone with malaria is said to feel good and is then expected to continue treatment with the decoction (Shirayama et al., 2006).On the Pacific Coast of Colombia, the leaves of mano, also known as guaco de mata or tres dedos (Anthurium cf.tridigitatum Engl.) are macerated and rubbed on the body as a rheumatic treatment for malaria (Blair & Madrigal, 2005).Similarly, the Achuar Jívaro of Peru apply hot leaves of a species of Monstera on the skin to relieve liver pain (Lewis et al.,1977;cited in Croat, 1994).
Therapeutic preparations often involve species from Araceae and other families.Corazón de Jesús or Jesus´s heart (Caladium bicolor Vent.) leaves are boiled in 1 L of water until half the volume evaporates and then lemon (Citrus × limon (L.) Osbeck) is added.The resulting liquid is allowed to sit to catch the morning dew and consumed on an empty stomach for 9 consecutive mornings in the treatment of inflamed liver (Blair & Madrigal, 2005).

Distribution of araceae species used in the treatment of malaria and related symptoms
Species of Araceae are used for the treatment of malaria and its symptoms throughout the tropical regions of the world (Figure 1).Poverty and lack of access to health services in many countries make these plants an important alternative for the treatment of malaria.Reports from the African nations of Ivory Coast, Kenya, Benin, Gabon and Togo have revealed eight antimalarial species belonging to the genera Amorphophallus Blume ex Decne, Anchomanes Schott, Culcasia P. Beauv., Homalomena Schott, Pistia L. and Pothos L. In the Amazon region, the largest numbers of Araceae species are used as antimalarials.The neotropical genera Philodendron Schott and Anthurium Schott are used by these Amerindian ethnic groups: Yanomami (Brazil), Tirios (Suriname), Wayãpi (French Guyana), Makuna and Miraña (Colombia)

Antiplasmodial activity and toxicity of species of araceae
Extracts of plants of the Araceae exhibit antimalarial potential and also cytotoxicity.The hexane and ethanol extracts of the stems of the aquatic plant aninga (Montrichardia linifera (Arruda) Schott) were inactive in vitro against P. falciparum Dd2 strain.However, the dichloromethane fraction of the ethanol extract exhibited high antiplasmodial activity (IC 50 < 10 µg/mL) and toxicity to the brine shrimp species Artemia salina (Amarante et al., 2011).M. linifera from Belém, Brazil exhibited leaf ethanol extracts with no toxicity to A. salina (DL 50 > 500 μg/mL) and moderate inhibition of P. falciparum W2 strain (IC 50 = 11.7 μg/mL) (Costa et al., 2009).
Water and ethanol extracts of the leaves of water lettuce (Pistia stratiotes L.) were apparently well-tolerated and exhibited antiarthritic and antipyretic effects in formalin-induced arthritis and LPS-induced fever in Sprague-Dawley rats (Kyei et al., 2012).On the other hand, the sap of Caladium bicolor is toxic and can even produce asphyxia (Flores et al. 2001).Isolation of the antiplasmodial and cytotoxic components from the extracts of plants of the Araceae is necessary for a better understanding of the medicinal potential of this family.

Chemistry of antimalarial species of araceae
Oxalic acid is frequently deposited as FIGURE 1. World locations where species of Araceae are used to treat malaria and its symptoms.Note: An orange colored point indicates where an Araceae species has been reported as being used to treat malaria or its symptoms.This mapa was generated based on the countries represented in Table 1.
crystals of calcium oxalate (Figure 2) in plants of the Araceae and is responsible for the toxicity of some genera (e.g.Dieffenbachia Schott).A large variety of anthocyanines have been identified in the flowers, fruit, leaves and leaf stems of 59 species of Araceae (Williams et al., 1981).The most commonly occurring pigment in these species was cyanidin 3-O-rutinoside, however, pelargonidin 3-rutinoside is also regularly found in the Araceae.
Leaves and branches of guaimbê-sulcado (Rhaphidophora decursiva (Roxb.)Schott) were extracted with methanol.The dry extract was defatted with hexanes.The chloroform soluble fraction of this extract was evaporated and chromatographed on silica gel using an acetone-chloroform gradient.Further normal phase, flash or reverse-phase chromatographies on the resulting fractions provided 14 compounds.Six of these compounds exhibited in vitro antiplasmodial activity (Zhang et al., 2001).The most active against P. falciparum D6 and W2 strains were the neolignan threo-polysyphorin (IC 50 = 404 and 368 ng/mL, respectively; Figure 2) and the benzoperoxide rhaphidecurperoxin (IC 50 = 540 and 420 ng/mL, respectively; Figure 2).The neolignans rhaphidecursinol A and B and lignans grandisin and epigrandisin were less active.To our knowledge, the above is the only report on antimalarial components from the Araceae.

FINAL REMARKS
A number of South American Araceae species are traditionally used in the treatment of malaria and its symptoms.Despite the in vitro inhibitory activity of extracts, fractions and isolated constituents against the human malaria parasite Plasmodium falciparum we found no in vivo antimalarial study in animal models for this family.Studies on the in vitro and in vivo antimalarial activity are needed to further explore the antimalarial potential of the Araceae.0), (554317/2010-9) and PQ (311.649/2011-4),respectively.

TABLE 1 .
Species of the Araceae family used in the treatment of malaria and malaria symptoms.

TABLE 1 .
Species of the Araceae family used in the treatment of malaria and malaria symptoms.

TABLE 1 .
Species of the Araceae family used in the treatment of malaria and malaria symptoms.Secoya and Tacana, and by African descendants (Pacific Coast, Colombia).Interestingly, no genus of antimalarial Araceae was reportedly used on both the African and American Continents thus providing evidence for the local distribution of the species used. and