Plants of the American continent with antimalarial activity

Plantas do continente Americano com atividade antimalárica

REVISÃO

Plants of the American continent with antimalarial activity

Plantas do continente Americano com atividade antimalárica

Ingrid R. Mariath; Heloina de S. Falcão; José M. Barbosa-Filho^*; Layanna C. F. de Sousa; Anna Cláudia de A. Tomaz; Leônia M. Batista; Margareth de Fátima F. M. Diniz; Petrônio F. Athayde-Filho; Josean Fechine Tavares; Marcelo S. Silva; Emídio Vasconcelos L. da Cunha

Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, Caixa Postal 5009, 58051-900 João Pessoa, PB, Brazil

ABSTRACT

Malaria is a human parasitic disease caused by protozoa species of the Plasmodium genus. This disease has affected populations of the tropical and subtropical regions. About 500 million new cases occur annually on the world and therefore it is considered an emerging disease of important public health problem. In this context, the natural products as vegetables species have their bioactive molecules as targets for pharmacological, toxicological and phytochemical studies towards the development of more effective medicines for the treatment of many diseases. So this work intends to aid the researchers in the study of natural products to the treatment of malaria. In this review, 476 plants of the American continent were related for the antimalarial activity and of these vegetables species 198 were active and 278 inactive for some type of Plasmodium when they were evaluated through of in vitro or in vivo bioassays models.

Keywords: Antimalarial activity, medicinal plants, natural products, American continent, review.

RESUMO

Malária é uma doença parasitária humana causada por protozoários do gênero Plasmodium. Esta doença tem acometido populações que habitam regiões tropicais e subtropicais. Anualmente, cerca de 500 milhões de casos ocorrem no mundo, o que permite ser considerada uma doença emergente de importância para a saúde pública. Neste contexto, os produtos naturais, a exemplo das espécies vegetais, têm suas moléculas bioativas como alvo para estudos farmacológicos, toxicológicos e fitoquímicos destinados à síntese de medicamentos mais eficazes para o tratamento de inúmeras doenças. Portanto, este trabalho fornece subsídio às pesquisas com produtos naturais para o tratamento da malária. Nesta revisão, 476 espécies de plantas do continente Americano foram relatadas para a atividade antimalárica, sendo destas 198 ativas e 278 inativas para algum tipo de Plasmodium, quando avaliados através de modelos in vitro e in vivo.

Unitermos: Atividade antimalárica, plantas medicinais, produtos naturais, continente Americano, revisão.

INTRODUCTION

Malaria is a parasitic disease caused by protozoa species of the Plasmodium genus and it is transmitted for human through the bite of infected female mosquito of the Anopheles genus (Veronesi, 1991). In each year, about 100 - 500 million people are infected while 1 - 3 million died with malaria in the world. This disease is considered a public health problem of global scale by World Health Organization (WHO, 1997). It is estimated that 40% of the population world lives in areas at risk of infection over 100 countries worldwide, which are include countries of the American continent (Trigger & Kondrachine, 1998).

In the South America, especially in Bolivia, the malaria is responsible for considerable number of morbidity and mortality. According to the Organización Panamericana de la Salud (OPS 1997), 0.7% of the Argentine population lives at risk of infection, but this percentage could still be higher because cross-border migration and the unrelated cases in the rural areas (Debenedetti et al., 2002). In Colombia, it was registered about 120,000 cases of malaria in the decade of 90, while in Brazil, 509.000 cases were recorded in this same period with 96% of them occurred in the Amazon region (WHO, 1997).

The main species of the genus Plasmodium involved on the transmition of the malaria for human are: P. vivax, P. ovale, P. falciparum and P. malaria. Therefore, the third specie is the most causer of death (Harrison et al., 1998). Other species of this genus infect animals as P. knowlesi (monkeys), P. berghei (rodents) and P. gallinaceum (fowl). The clinical events are fever, feeling of malaise, chills, muscle pain, fatigue, anemia, compromised liver, spleen and kidney and they occur between 9 and 40 days after the bite of the infected mosquitoes, depending on the species of Plasmodium (Neves et al., 2005).

The treatment with single or combined drugs resistant to chloroquine has been used as an alternative therapy for malaria, but they are expensive and sometimes cause signal of toxicity due to limited knowledge about the metabolism and mechanism of action of these antimalarial drugs. However, all these medicines are still are essential to reduce the morbidity and mortality caused by malaria, since the vaccine against this disease have limited activity in humans. Therefore, it is necessary to develop new, safe and effective antimalarial medicines. So in recent years, there has also been growing interest in alternative therapies such the use of natural products, especially those derived from plants which have showed to produce promising results for the treatment of many diseases (Rates, 2001). In this context, the present work is a review about plants of the American continent with antimalarial activity.

In the course of our continuing search for bioactive natural products from plants, we have recently published reviews of extracts and compounds derived of plants with the following potential activities: inhibitors of mammary, uterine cervical and ovarian neoplasia (Moura et al., 2001; Moura et al., 2002; Silva et al., 2003); inhibitors of HMG CoA reductase (Gonçalves et al., 2000); with central analgesic activity (Almeida et al., 2001); employed in prevention of osteoporosis (Pereira et al., 2002); for the treatment of Parkinson's disease (Morais et al., 2003); anticonvulsant and anxiety disorders (Quintans-Junior, 2008; Sousa et al., 2008), with antileishmanial (Rocha et al., 2005), giardicidal (Amaral et al., 2006), antileprotic (Barbosa-Filho et al., 2007a), hypoglycemic (Barbosa-Filho et al., 2005) and anti-inflammatory (Falcão et al., 2005; Barbosa-Filho et al., 2006a) activities; inhibitors of the acetylcholinesterase and angiotensin-converting enzyme (Barbosa-Filho et al., 2006b; Barbosa-Filho et al., 2006c), and with antiulcer activity (Falcão et al., 2008a,b; Mota et al., 2009). Our group has also reviewed the medicinal and poisonous plants of the Northeastern region of Brazil (Agra et al., 2007, 2008), among other review articles (Alves et al., 2000; Souza et al., 2005; Gonçalves et al., 2006; Barbosa-Filho et al., 2007b, 2008; Sena-Filho et al., 2008).

MATERIALS AND METHODS

In this article, some reports about vegetable species of the American continent with antimalarial activity were reviewed in the specialized literature published up to December 2007. The search was carried out on data banks such as Biological Abstracts, SciFinder Scholar, Periódicos CAPES, Pubmed and NAPRALERT (acronym for Natural Products ALERT - University of Illinois in Chicago, U.S.A.). The references were consulted for details of the experimental models used for testing the extracts and derivates vegetables against malaria, activities and organism tested.

RESULTS AND DISCUSSION

For this review, 476 species of plants were listed with possible antimalarial activity and distributed in 103 botanical families. Among those plant species 198 were active and 278 inactive against some Plasmodium type causer of malaria when evaluated in vivo or in vitro bioassays models. The antimalarial activity was evaluated for P. falciparum, P. berghei, P. gallinaceum, P. vinckei, P. lophurae, P. cathemerium and P. yolii stains. The most studied botanical families were Asteraceae, Simaroubaceae, Fabaceae, Meliaceae, Amaryllidaceae, Apocynaceae, Rubiaceae, Velloziaceae and Verbenaceae which showed more than ten species of plants studied. The main studies were developed in Brazil and United States due to the flora biodiversity offered by the first country or the financial-technology resource of the second one. All data are shown in Table 1.

Some researches are validation of the tradicional medicine with the use of plants for the treatment of malaria. Remijia ferruginea (Rubiaceae) of which the 80 % ethanol extract obtained of the dried bark at the dose of 500 mg/kg was active against P. berghei infected mice (Andrade-Neto et al., 2003) and Bidens pilosa (Asteraceae), one plant used in the Brazilian endemic area, showed antimalarial activity to different extracts obtained of dried entire plant, leaves, root or stem against P. falciparum and P. berguei through of in vitro and in vivo bioassays models (Brandão et al., 1997; Krettli et al., 2001a,b; Oliveira et al., 2004). Other species of the Asteraceae family is Vernonia brasiliana in which the hexane extract of dried leaves decreased the infection of P. berghei in mice and it was inactive for P. falciparum in vitro model (Carvalho & Krettli, 1991; De Almeida Alves et al., 1997); the decoction and aqueous extract of Acanthospermum australe inhibited in vitro the growth of P. falciparum stain or decreased the infection caused by P. berghei in mice (Brandão et al., 1992; Carvalho & Krettli, 1991; Carvalho et al., 1991). Species of the Artemisia genus also were studied for antimalarial activity such A. absinthium, A. vulgaris and A. ludoviciana. In the researches, the aqueous extract of the first and second plant did not inhibit in vitro the growth of P. falciparum (Hernandez et al., 1990), while the 95% ethanol extract of the last specie was active against P. yoelii infected mice (Malagon et al., 1997).

The vegetables species of the Cucurbitaceae family were also evaluated to this activity. So the 95% ethanol extract obtained from the dried seed of Cucurbita maxima popularly known as pumpkin strawberries was active in dose of 250 mg/kg against P. berghei infected mice (Amorim et al., 1991) and Momordica charantia, called as melon from São Caetano, had the aqueous and chloroform extracts obtained of the dried flowers or aerial parts inactive against P. berghei, P. gallinaceum, P. cathemerium and P. lophurae (Carvalho et al., 1991; Spencer et al., 1947), the 95% ethanol extract obtained of the dried leaves in the dose of 500 mg/kg was also inactive against P. berghei infected mice (Amorim et al., 1991), while the infusion and 95% ethanol extract of the dried leaves and stem in dose of 1.0 g/kg were active against P. berghei infected human or mice (Ueno et al., 1996).

Lantana cujabensis Schauer (Verbenaceae) is a shrub found in the Amazonian and Andean forests of South America. Okunade & Lewis (2004) related that the 95% ethanol extract obtained of the dried leaves and stem of this plant had antimalarial activity in vitro against P. falciparum. Mcphail et al. (2007) evaluated the antimalarial activity of the ethyl acetate extract of marine cyanobacterium Lyngbya majuscula (Oscillatoriaceae) in vitro model for P. falciparum. This extract in the concentration of 2.0 μg/mL inhibited the growth of the protozoa.

Plant species of the Fabaceae family were also evaluated such Bowdichia virgilioides which is traditionally used against malaria by American natives had the 95% ethanol extract obtained of the dried bark active in dose of 250 mg/kg to P. berghei infected mice and in vitro to P. falciparum - MRC 20 (IC₅₀ = 1 μg/mL) and P. berghei (IC₅₀ = 0.2 μg/mL). In similar, Caesalpinia pluviosa also had the 95% ethanol extract of the dried bark active in the dose of 500 mg/kg to P. berghei infected mice and in vitro to P. falciparum - MRC 20 (IC₅₀ = 15 μg/mL) and P. berghei (IC₅₀ = 8.3 μg/mL).

Species of plants of the Lauraceae family such Nectandra aff. hihua and Licaria canella had the 95% ethanol extract active when evaluated against P. falciparum - MRC 20 and P. berghei in vitro and in vivo bioassays models. However, the 95 % ethanol extract of the dried bark of Protium glabrescens (Burseraceae) in the 100 mg/kg dose was only active in vivo model to P. berguei, while it was inactive in vitro model to P. falciparum - MRC 20 and P. berghei (Deharo et al., 2001).

Also were related in scientific literature some species of the Solanaceae family with antimalarial activity. The plant Solanum nudum has been used by American community as Tumaco in Colombia to cure malaria and in according to Marcela et al. (2001), the aqueous extract obtained of the dried leaves and stem (0.3 % w/v - i.p.) was active against the P. berghei infected mice. The 95% ethanol extracts of the dried leaves of Dunalia brachyacantha and Saracha punctata were tested in vitro models for P. falciparum, so the first plant was active while the second one showed inactive. Both the extracts also were evaluated in vivo models to P. vinckei and all were active (Moretti et al., 1998; Munoz et al., 2000). However, the 95% ethanol and hexane extracts of Acnistus arborescens did not have this activity for P. berghei stain (Brandão et al., 1985).

Picrasma crenata (Veil.) Engl. (Simaroubaceae) is known as 'granadillo' or 'quasia', 'palo amargo' in Argentina and it is indicated such an antimalarial, febrifuge, tonic, antisyphilitic and insecticide. The aqueous and methanol extracts of the dried aerial parts this plant showed antimalarial activity in vitro for P. falciparum K-1 (Debenedetti et al., 2002). Other species from this botanical genus such P. excelsa and P. antillana did not have this activity for P. gallinaceum infected chicken when the methanol and chloroform extracts obtained from the wood were used (Spencer et al., 1947).

Other species used by American population did not have antimalarial activity in condition evaluated. Such the 80% ethanol extract of Strychnos pseudoquina (Loganiaceae) in the dose of 1,000 mg/kg (Andrade-Neto et al., 2003) and the aqueous extract obtained from the dried bark of Coutarea hexandra (Rubiaceae) when it was evaluated to P. berghei infected mice (Carvalho et al., 1991). In similar, Deianira erubescens (Gentianaceae) also did not show activity with the 80% ethanol extract obtained from the dried leaves and root (Andrade-Neto et al., 2003). The aqueous extract of the dried leaves of Lisianthus speciosus was active against P. berghei infected mice and in vitro for P. falciparum stain (Carvalho & Krettli, 1991), while the same extract obtained of the dried root was inactive for P. berghei infected mice (Carvalho et al., 1991). In study elaborated by Diaz & Medina (1996), the chloroform extract obtained from the dried stembark of Tabebuia ochracea ssp. neochrysantha (Bignoniaceae) which is traditionally used against malaria in the Amazon did not show bioactivity in vitro against P. berghei.

CONCLUSION

Plants represent a vital source to research new active principles for the treatment of human diseases such as malaria which is considered neglected and emergent in American countries because the high incidence of attacks of the female Anopheles mosquitoes infected with Plasmodium spp at risk of infection regions such the forests areas. In this paper a variety of plants of the American continent evaluated against the main protozoa causer of the malaria was related. However, we conclude that the plants with antimalarial activity are a few and they do not have this therapeutic property fully defined. Therefore, in this context, it is necessary to support financially the multidisciplinary and interdisciplinary research, mostly those related to natural products enabling the discovery of new antimalarial pharmaceuticals.

ACKNOWLEDGMENTS

The authors thanks to College of Pharmacy, the University of Illinois at Chicago, U.S.A., for helping with the computer database NAPRALERT. And are grateful to CNPq and CAPES for financial support and research fellowships.

Received 30 December 2008

Accepted 1 March 2009

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Publication Dates

• Publication in this collection
  11 Aug 2009
• Date of issue
  Mar 2009

History

• Received
  30 Dec 2008
• Accepted
  01 Mar 2009