Plants used traditionally to treat malaria in Brazil: the archives of Flora Medicinal
Abstract
The archives of Flora Medicinal, an ancient pharmaceutical laboratory that supported ethnomedical research in Brazil for more than 30 years, were searched for plants with antimalarial use. Forty plant species indicated to treat malaria were described by Dr. J. Monteiro da Silva (Flora Medicinal leader) and his co-workers. Eight species, Bathysa cuspidata, Cosmos sulphureus, Cecropia hololeuca, Erisma calcaratum, Gomphrena arborescens, Musa paradisiaca, Ocotea odorifera, and Pradosia lactescens, are related as antimalarial for the first time in ethnobotanical studies. Some species, including Mikania glomerata, Melampodium divaricatum, Galipea multiflora, Aspidosperma polyneuron, and Coutarea hexandra, were reported to have activity in malaria patients under clinical observation. In the information obtained, also, there were many details about the appropriate indication of each plant. For example, some plants are indicated to increase others' potency. There are also plants that are traditionally employed for specific symptoms or conditions that often accompany malaria, such as weakness, renal failure or cerebral malaria. Many plants that have been considered to lack activity against malaria due to absence of in vitro activity against Plasmodium can have other mechanisms of action. Thus researchers should observe ethnomedical information before deciding which kind of screening should be used in the search of antimalarial drugs.
1. Background
Flora Medicinal is an ancient and small pharmaceutical laboratory established, in early 1915, by Mr. José Monteiro da Silva, a Medical Doctor in Rio de Janeiro. Mr. Monteiro da Silva was an idealist who believed that the Brazilian rainforest had an enormous potential for research and discovery of new drugs. For more than 40 years Mr. Monteiro da Silva had organized a group of technicians and scientists who made a great number of excursions into Brazilian rainforest, collecting plant specimens and information. Although he had also edited the Revista da Flora Medicinal, a scientific paper in which he described his discoveries, a considerable part of his research remains unpublished. During the '30 s and '40 s, the Revista da Flora Medicinal was translated to French and republished by the Institut Pasteur, in Paris, which allowed some of his findings to be used by the international pharmaceutical industry. During his activities, Mr. Monteiro da Silva and his team described more than 200 new medicinal plants from this region. One of his targets was the study of new antimalarial plants, as at his time malaria was a concerning health problem in Brazil. In the following years, quinine, its derivatives and other drugs helped to control malaria. Nowadays, however, its incidence is again growing worldwide, and Plasmodium falciparum is getting more resistant to the usual antimalarial drugs[1]. It is estimated that 62% of P. falciparum around the world presents with mono or multiresistant drug profile[1]. The World Health Organization estimates that there are between 300 and 500 million new cases of malaria worldwide, every year, mostly in Africa, Asia, South Pacific Islands and South America, which causes, at least, 3 million deaths[2,3]. The main drugs developed for malaria and used up to now (quina alkaloids derived drugs and artemisinin) were discovered based on traditional use and ethnomedical data[4,5]. New efforts to search for novel drugs for treating malaria are very important in countries like Brazil, where many endemic areas still exist[6]. The study of well-documented data such as the archives of Flora Medicinal can point out traditional and probably effective treatments that had not been yet subjected to testing.
2. Materials and methods
All documents, including books, hand notes, unpublished studies and the issues of Revista da Flora Medicinal, belonging to the library of Mr. Monteiro da Silva, were examined for information about botanical therapies and plant species used for malaria. Any data or references to plants used for malaria were carefully inserted into a template, and botanical name and classification were re-examined and confirmed with four major plant databases – The Missouri Botanical Garden's VAST[7], the International Plant Names Index[8], the New York Botanical Garden vascular plants database[9] and the Brazilian's Northeast Plants Database[10]. Other information existing in modern databases such as Pubmed (U.S. National Library of Medicine's database that is searchable on the Web) were also examined and compared to other ethnopharmacological studies and current published data.
A review of plants with possible antimalarial activity reported in ethnomedical studies or in pharmacological and biochemical research was also made [11-31].
3. Results
The results are summarized on Table 1. Forty [40] plants with possible antimalarial activity were reported and examined by Dr. Monteiro da Silva and his co-workers. The plants were identified by scientific names and families, as well as by vernacular names and usual translations to English, if existent. For each of the species, the parts used for general conditions and symptoms and for treating malaria, as gathered from ethnomedical reports published in Flora Medicinal, are listed. Scientific data about in vitro and in vivo research are also provided.
Scientific name and family | Vernacular name | Part used | General indications found in ethnomedical studies | Information regarding use for malaria | Scientific data on anti-malarial activity | Origin and geographic distribution | Ref. |
Aniba canelilla (H.B.K.) Mez. (Lauraceae) | Preciosa, Casca preciosa, Pau rosa, Casca do Maranhão, Rosewood, Brazilian rosewood | Barks and leaves | Arthritis, fever, colic, heart problems, dyspepsia, infection, intermittent fevers, weakness, malaria, leukorrhea, chronic discharge. Thoracic, stimulant. | Dr. Monteiro da Silva indicates that Amazon Indians used this plant to treat malaria. | Large tree that occurs in the Amazon and Atlantic Forest. | (32) | |
Acanthospermum australe (Loefl.) Kunt. (Asteraceae) | Amor de negro, Mata-pasto, Picão da praia, Picão da prata, Paraguayan starburr | Leaves and roots | Fever, malaria, diarrhea, erysipelas, anemia, urinary infections, blennorrhea, bronchitis, dyspepsia. Tonic, diaphoretic, eupeptic, antidiarrheal, mucilaginous, antimalarial, antiblennorrhagic. | Dr. Monteiro da Silva indicates this plant as a substitute for quina and reports that doctors have a good outcome when using this species in malaria. | Plants of the same genus used to treat malaria in Africa showed antiplasmodial activity against P. falciparum in vitro. | Herbaceous, invasive and ruderal plant that usually invades crops and occurs spontaneously in the Cerrado. | (33,34) |
Aristolochia cymbifera Mart. & Zucc. (Aristolochiaceae) | Jarrinha, Mil homens | Roots | Asthma, fever, diarrhea, dyspepsia, gout, infection, amenorrhea, orchitis, intermittent fevers. | Dr. Monteiro da Silva reports that this must be associated to Cayaponia tayuya for use in malaria. | (35,36) | ||
Aspidosperma polyneuron Müll. Arg. (Apocynaceae) | Peroba rosa, Sobro, Peroba amargosa | Barks | Fever, diarrhea. Febrifuge, antimalarial, astringent. | Indicated for malaria in the Flora Medicinal literature. Plant contains alkaloids with antimalarial action. Cases of malaria controlled with this bark are reported. | Its alkaloids were extensively studied. | (37) | |
Bathysa cuspidata (St. Hil.) Hook. f. (Rubiaceae) | Quina do mato | Barks | Febrifuge, bitter tonic, eupeptic used as a substitute for quina in malaria | Indicated for malaria in the Flora Medicinal literature. | Tree that occurs in the Atlantic Rainforest. | (38) | |
Bidens pilosa L. (Asteraceae) | Picão, Picão preto, Erva picão, Cuambu, Farmer's Friend, Cobbler's pegs, Beggar's ticks, Pitchforks, Hairy beggarticks | Leaves | Jaundice, fever, hepatitis, leukorrhea, diarrhea, pharyngitis, worms, cough, pneumonia, hepatomegaly. Mucilaginous. | Indicated in many medical texts in the past for malaria. Dr. Monteiro da Silva used for patients that did not respond to quinine. | Preclinical tests revealed strong antiplasmodial activity. | Plant with worldwide distribution. | (33,39) |
Cosmos sulphureus Cav. Syn. Bidens sulphurea (Cav.) Sch. Bip. (Asteraceae) | Picão de flor grande, Picão grande, Beijo de moça, Cosmo amarelo, Yellow cosmos, Klondike Cosmos, Sulphur cosmos, Orange cosmos | Fruits and aerial parts | Jaundice, intermittent fever, splenomegaly. Tonic, hepatic, hepatoprotective. | Indicated for malaria in the Flora Medicinal literature. | Plant bred with ornamental purposes. | (33) | |
Cassia fistula L. (Leguminosae Caesalpinioideae) | Chuva de ouro, Cássia amarela, Cássia imperial, Canafístula, Golden shower, Indian laburnum, Purging fistula, Drumstick tree | Barks, leaves and seeds | Poisons, erysipelas. Febrifuge, purgative, emmenagogue, diuretic, hepatic, skin problems. | Indicated by Dr. Monteiro da Silva as an adjuvant for the treatment of malaria. | Ornamental plant found all over Brazil. | (32) | |
Catharanthus roseus (L.) G. Don. (Apocynaceae) | Vinca, Boa noite, Lavadeira, Vinca rósea, Cape periwinkle, Catharanthus, Church flower, Madagascar periwinkle, Red periwinkle, Rosy periwinkle | Aerial parts | Diabetes, urinary infection, malaria, intermittent fever. Sudorific, diuretic, hypoglycemic, febrifuge. | Indicated as a substitute for quina by Dr. Monteiro da Silva. | Ornamental plant used by the pharmacy industry for obtaining alkaloids. | (33) | |
Cecropia hololeuca Miq. (Cecropiaceae) | Emabaúba, Imbaúba, Embaúba branca, Embaúba prateada, Trumpet tree, Silver embauva, Black embauva, White embauva | Leaves, fruit and sprouts juice | Diuretic, antihypertensive, sedative, refreshing, antiinflammatory, thoracic, healing, expectorant antiasthmatic, cough suppressant, resolutive, antithermal. | Indicated by Dr. Monteiro da Silva as an adjuvant in malaria with very high fever or neurological symptoms. | Tree that occurs in the Atlantic Rainforest. | (40) | |
Cedrela fissilis Vell. (Meliaceae) | Cedro rosa, Cedro vermelho, South American cedar | Barks | Swamp fever, urinary infection, diarrhea. Aromatic, astringent, diuretic, depurative, febrifuge. | Indicated for malaria in the Flora Medicinal literature. | Plant that occurs in the Atlantic Forest. | (41) | |
Chondodendron platyphyllum (St. Hill.) Miers. (Menispermaceae) | Abútua, Bútua, Uva do mato | Roots, barks and leaves | Gases, colic, diarrhea, abdominal pain, verminosis, fever, emesis, nausea, infection, bronchitis, amenorrhea, intermittent fever. Antiasthmatic, bitter tonic, eupeptic. | Use by Indians from the Tupi-Guarani tribe for treating malaria, reported by Dr. Monteiro da Silva. | Isoquinolinic alkaloid-rich plant with antiparasitary activity, natural from the Atlantic Forest. | (42,43) | |
Cinchona calisaya Wedd. (Rubiaceae) | Quina peruana, Casca dos jesuítas, Quina verdadeira, Ledger quinine, Calisaya, Jesuit's powder, Yellow cinchona | Barks | Fever, malaria, eczema. Hair tonic. | Used as the main source of quinin by Dr. Monteiro da Silva. It has quinolinic and quinin derivatives in its composition. | Originary from the Amazon. | (38,44) | |
Coffea arabica L. (Rubiaceae) | Café, Cafeeiro, Coffee, Arabica coffee, Arabian coffee, Abyssinian coffee, Brazilian coffee | Leaves and seeds | Colds, intermittent fever. Clears the blood, diuretic, stimulant, antiasthmatic, digestive, hypoglycemic. | Dr. Monteiro da Silva used the leaves decoction to potentiate other plants with anti-malarial activity. | Plant with African origin, adapted to Brazil. | (45) | |
Coutarea hexandra (Jacq.) Schum. (Rubiaceae) | Quina-quina, Quina-brava, Quina-de-pernambuco, Quineira, Murta do mato | Barks | Intermittent fever, gallbladder stones or problems, digestive problems, colic. Antithermal, antimalarial. | Dr. Monteiro da Silva relates this plant as one of the substitutes for quina and reports cases of malaria cure with its use, some described in the book Botânica Médica Cearence, from Dr. Francisco Dias da Rocha. | Plant from the Cerrado used for ornamental purposes. | (33) | |
Cuphea ingrata Hoehne (Lythraceae) | Sete sangrias, Perna de saracura, Mata cana, Pega pinto | Aerial parts and whole plant | High blood pressure, syphilis, dermatoses, intermittent fever, stomachache, rheumatism, venereal diseases, urethral discharge. Depurative, antisyphilitic, cholesterol-reducing, antihemorrhagic, mucous membrane protector, tonic, analgesic. | Indicated for malaria in the Flora Medicinal literature. According to Dr. Monteiro da Silva co-workers, this plant potentiates other antimalarial extracts and help preventing renal and cerebral complications in severe cases. | Herbaceous and ruderal plant that occurs in almost all regions of Brazil, used also for ornamental purposes. It is described in all South and Central America. | Personal writings and archives of Mr. Monteiro da Silva. | |
Dipteryx odorata (Aublet) Willd. (Fabaceae) | Fava de Tonka, Faveira de cheiro, Imburana de cheiro, Cumaru de cheiro, Cumaru de folha grande, Tonka bean, Cumaru, Coumarou, Tonquin bean | Seeds | Antispasmodic, emmenagogue, analgesic, febrifuge, brain stimulating. | In a review, Dr. Monteiro da Silva points this species as having potential use in malaria based on ethnopharmacological reports obtained in his expeditions. | Plant from the Amazon that is rich in coumarins, which gives it a special odor, and for this reason it has been used in the food and tobacco industry as an odorizing agent. | (32) | |
Elephantopus mollis Kunth. (Asteraceae) | Erva grossa, Língua de vaca, Pé de elefante, Elephantopus, Elephant's foot, False tobacco, Tobacco weed | Aerial parts | Fever, jaundice, gallstone, diarrhea, herpes, syphilis, colds, flu, rheumatism, general pruritus. Tonic, depurative. | Indicated for malaria in the Flora Medicinal literature. Some doctors suggest that this plant could be tried if no chinchona bark or substitute is available. | Herbaceous and ruderal plant that is found all over Latin America. | (41) | |
Erisma calcaratum (Link) Warm. (Vochysiaceae) | Jaboti, Erva de Jaboti, Jabuti, Jabuti-araconha, Jabuti da várzea, Jaboty, Jaboty palm | Fruits | Skin infections, dermatoses, fever, malaria. Oleaginous, resolutive. | Reported in review as a plant used by the Amazonian Indians for the treatment of malaria. | Medium sized tree that grows along the moist lowlands of the Amazon. | (32) | |
Esenbeckia febrifuga (St. Hil.) A. Juss. ex Mart. (Rutaceae) | Quina do mato, Angustura, Gumarim | Barks | Malaria, intermittent fever, adenitis, constipation, dyspepsia. Bitter tonic, febrifuge. | Indicated for malaria in the Flora Medicinal literature. | Tree natural from the Southern and Southeast regions. | (38) | |
Galipea multiflora Schultz (Rutaceae) | Quina falsa, Jasmim do mato, Ticoró, Guamixinga | Barks | Dyspepsias, gastric atony, fever, infections, malaria. Tonic, astrigent, bitter, eupeptic, febrifuge, antidiarrheal. | Reported as a substitute for quina in the treatment of malaria in a review by Dr. Monteiro da Silva. Effective in malaria, but weaker than Peruvian chinchona. | Tree that occurs in the Cerrado and Atlantic Forest. | (32,38) | |
Geissospermum sericeum (Sagot) Benth (Apocynaceae) | Pau pereira, Quinarana, Pau forquilha, Acariranha | Barks | Dermatoses, inflammations, swamp fevers. Bitter tonic. | Reported in a review as being a plant tested and approved by doctors for malaria. | Alkaloids with activity against Plasmodium falciparum were isolated from trees of the genus Geissospermum. | Species from the Atlantic Forest. | (32,42,46) |
Gomphrena arborescens L. (Amaranthaceae) | Paratudo, Paratudinho, Perpétua raiz do padre | Leaves, flowers and tuberous roots | Weakness, colitis, fevers, mental fatigue, intermittent fevers. Antithermal, antidiarrheal, febrifuge, tonic, emmenagogue, aromatic, eupeptic, antitoxic, protector. | Indicated for malaria in the Flora Medicinal literature. Use in malaria introduced by Brazilian priests that learned it from Indians. | Plant natural from the central region (Cerrado) of Brazil, sometimes cultivated as ornamental. | (47) | |
Himatanthus lancifolius (Mull. Arg) Wood. Syn. Plumeria lancifolia Müll. Arg. (Apocynaceae) | Agoniada, Plumeria, Agonium, Arapuê | Barks | Menstrual cramps, fever, hysteria, gastric atony, malaria. Purgative, antispasmodic. | Use for malaria described by Pekolt among Guarani Indians. | Plant that occurs in the Cerrado and Atlantic Forest. | (48) | |
Jateorhiza palmata Miers. (Menispermaceae) | Calumba, Calunga | Barks | Flatulence, colic, diarrhea, abdominal pain, verminosis, fever, emesis, nausea, infection, hypertension, bronchitis, dyspepsia, digestive atony. Bitter tonic, eupeptic. | Plant rich in quinolinic alkaloids with antiparasitary potential. | Exotic plant, natural from Africa, adapted to Brazil. | (41) | |
Melampodium divaricatum (L.C. Rich.) DC. (Asteracea) | Picão da praia, Fel da terra, Salsa da praia, Butter daisy | Leaves | Fever, malaria, flatulence, stomachache, colics, joint pain, muscular pain, palpitation, vertigo, rheumatism, jaundice, anuria. Diuretic, carminative. | Dr. Monteiro da Silva reports many cases of malaria cure using the extract of this plant. | Worldwide distribution. | (32,49) | |
Mikania glomerata Spreng. (Asteracea) | Guaco, Coração de Jesus, Erva de cobra, Cipó almecega | Leaves and flowers | Rheumatism, snake poison, intestinal problems, colics, dysmenorrhea, fever, malaria. | Dr. Pires de Almeida reports to have observed Indians using this plant for malaria with good outcomes. | Liana that is common in the Atlantic Forest. | (50,51) | |
Musa paradisiaca L. (Musacea) | Banana, Bananeira | Stem juice | Worms, diarrhea, intermittent fever, weakness. Tonic, antidiarrheal, thoracic, expectorant, nutritive. | Indicated by Dr. Monteiro da Silva to potentiate other plants used in malaria and help in the recovery of patients. | Exotic plant adapted to Brazil. | (52) | |
Ocotea odorifera (Vell.) Rohwer Syn.Ocotea pretiosa (Nees) Mez (Lauraceae) | Sassafraz, Canela de sassafraz, Sassafraz do Brasil, Brazilian sassafras | Barks and roots | Dermatoses, joint pain, fever, rheumatism, syphilis, gout. Sudorific, depurative. | Indicated for malaria in the Flora Medicinal literature. One of the plants used by Guarany Indians to treat fever and malaria. | Species form the Atlantic Forest. | (41) | |
Picrolemma sprucei Hook. f. (Simaroubacea) | Caferana, Caferana verdadeira | Aerial parts and roots | Malaria, intermittent fevers. Sudorific, depurative, febrifuge, antiinfectious. | Dr. Monteiro da Silva reports many cases of recovery from malaria after treatment with the extract of this plant. | Shrub that grows on solid ground in the Amazon. | (49) | |
Pradosia lactescens (Vell.) Radlk. (Sapotaceae) | Bunhanhém, Pau de remo, Pau doce, Guaranhém, Monesia | Barks | Discharge, bronchitis, hemoptysis, diarrhea, ocular inflammation, tuberculosis, cutaneous ulcers, metrorrhagia. Bark provides a milky juice that is astringent and tonic. | Indicated for malaria in the Flora Medicinal literature. According to Dr. Monteiro da Silva, this plant could be associated to any antimalarial therapeutic drug if the patient is not recovering quickly. | Species from the Atlantic Forest. | Personal writings and archives of Mr. Monteiro da Silva. | |
Quassia amara L. (Simaroubacea) | Quassia, Casca amargosa, Pau amargo, Pau de surinã, Quassia-wood, Surinam quassia, Bitter quassia, Bitterwood | Barks | Gastric debility, dyspepsia, blennorrhea, flatulence, fever, malaria, diarrhea, worms. Bitter tonic. | According to a survey by Dr. Monteiro da Silva, it is used by Indians from the North of Brazil and from Suriname for treating malaria. | Extracts showed antimalarial activity in experimental malaria in mice. | Plant from the Amazonian Rainforest. | (53,54) |
Remijia ferruginea A. St. Hil. (Rubiaceae) | Quina mineira | Barks | Intermittent fever, malaria. | Cited by Dr. Monteiro da Silva as one of the species popularly used to substitute quina in the treatment of malaria. | Tested in mice with experimental malaria caused by P. berghei, with reduction of 98% of infected red blood cells. | Medium sized tree that occurs in Atlantic Rainforest and South Amazonia. | (33,55) |
Simaba ferruginea A. St. Hil. (Simarubacea) | Calunga | Barks and roots | Malaria, fevers, diarrhea. Tonic, eupeptic, febrifuge, antidiarrheal, diuretic. | Indicated for malaria in the Flora Medicinal literature. According to Peckolt, it was used by Amazonian Indians to treat malaria. | A quassinoid isolated from Simaba sp showed activity against Plasmodium falciparum in vitro. | Huge tree from the Amazon Forest. | (41,56) |
Simarouba amara L. (Simaroubacea) | Calunga, Marubá, Marupá, Dysentery bark, Bitterwood, Slave wood, Bitter damson | Barks and roots | Intestinal infections, verminosis, fever, wounds, infected ulcers, abdominal pain. Antidiarrheal, antispasmodic, healing. | Used by Amazonian Indians to treat fever and malaria. According to Dr. Monteiro da Silva, it can be used in cases with neurological signs. | Big size tree that occurs in the Atlantic Rainforest and South Amazonia. | Personal writings and archives of Mr. Monteiro da Silva. | |
Strychnos pseudoquina A. St. Hil. (Loganiaceae) | Quina do campo, Quina branca, Quineira, Quina-grossa, Quina do cerrado | Barks | Splenomegaly, hepatomegaly, intermittent fever, malaria, gastric problems. Tonic, bitter, febrifuge, depurative. | Cited by Dr. Monteiro da Silva as one of the species popularly used to substitute quina in the treatment of malaria. According to Andrade-Neto, its potency is inferior to Peruvian quina bark and must be associated with other antimalarial plants. | In a test with experimental malaria in chicken caused by P. berghei, no activity was found. | Shrub from the Cerrado that produces edible fruits. | (33,38,55) |
Tabebuia avellanedae Lor. Ex Griseb. (Bignoniaceae) | Ipê roxo, Pau d'arco, Trumpet tree | Barks | Fever, tumors, allergy, weakness, psoriasis. Antiinfectious, antifungic, anticancer, tonic, immunestimulant. | Indicated for malaria in the Flora Medicinal literature. Should be added to antimalarial regimens for weak patients or in cases of renal failure. | Tree that occurs in the Cerrado and Atlantic Rainforest, with strong medicinal uses. | Personal writings and archives of Mr. Monteiro da Silva. | |
Tachia guianensis Aubl. (Gentianacea) | Jacaruaru, Quassia do Pará, Caferana, Tinguá-aba | Branches and roots | Infections, abdominal pain, worms, malaria. Digestive, antiinflamatory, febrifuge. | One of the plants cited by Dr. Monteiro da Silva as having potential for treating malaria. Plant used in Amazon by Indians to treat malaria. | Personal writings and archives of Mr. Monteiro da Silva. (47) | ||
Tabebuia impetiginosa Syn. Tabebuia roseo-alba (Bignoniaceae) | Ipê preto, Ipê roxo, Ipê rosa, Trumpet tree | Barks | Fever, tumors, malaria, parasitosis. Antiinfectious, antifungic, anticancer, tonic, immunestimulant. | Indicated for malaria in the Flora Medicinal literature. Should be added to antimalarial regimens for weak patients or in cases of renal failure. | Tree that occurs in the Cerrado and Atlantic Rainforest, with strong medicinal uses. | Personal writings and archives of Mr. Monteiro da Silva. | |
Xylopia brasiliensis Spreng. (Annonaceae) | Embira de caçador, Pindaíba | Seeds and barks | Stomachaches, flatulence, malaria. Stomachic, carminative, febrifuge. | Indicated for malaria in the Flora Medicinal literature, but Dr. Monteiro da Silva considered it a weak antimalarial drug. | Xylopia sp extracts proved active against P. falciparum with IC50 between 3 and 10 mcg/ml. | Plant that occurs in the Cerrado and Atlantic Forest. | Personal writings and archives of Mr. Monteiro da Silva. (57) |
Most plants, like Bidens pilosa, Cantharanthus roseus, Cassia fistula, Cinchona calisaya, Cuphea ingrata, Geissospermum sericeum, Jateorrhiza palmata, Quassia amara, Simaba ferruginea, and Strychnos pseudoquina, were already reported as antimalarial in previous ethnobotanical studies. Some of these had also their activity against Plasmodium tested, as shown on Table 1. Eight species are reported as antimalarial for the fist time: Bathysa cuspidata, Cosmos sulphureus, Cecropia hololeuca, Erisma calcaratum, Gomphrena arborescens, Musa paradisiaca, Ocotea odorifera, and Pradosia lactescens.
A greater proportion of the plants reported as antimalarial belong to the families Asteraceae (six species), Rubiaceae (five), Apocynaceae (four), and Simaroubaceae (four).
4. Discussion
Most research for antimalarial new drugs is only focused on direct activity against Plasmodium species. But attention to ethnomedical information gathered by Monteiro da Silva suggests that other effects should be investigated. For example, some plants are referred to enhance the action of other herbs, which can indicate an increase on permeability of the Plasmodium membrane to antiparasitic substances, or an inhibition of pump mechanisms of eliminating the drugs[58,59]. Considering that one of the common mechanisms of drugs resistance is the reduction of permeability, the development of drugs that enhance parasite permeability could be of valuable help in the treatment of infectious diseases[60,61]. Other possible mechanism of action is interference with parasite enzymes used for protection against antiparasitic drugs[62].
Some plants with noticeable ethnopharmacological use in malaria showed only weak or even no activity against Plasmodium in vitro[55]. For example, Mikania glomerata, Melampodium divaricatum, Galipea multiflora, Aspidosperma polyneuron, and Coutarea hexandra had their antimalarial activity confirmed by clinical observations of medical doctors (Table 1), an information that yields a high probability of accuracy.
Some authors have underestimated the traditional plants used for malaria based exclusively on low activity against Plasmodium in vitro or in animal models[55]. This can be a mistake of strategy or even methodology.
There are many explanations for the absence of in vitro activity of an effective antimalarial drug. As an example, the active principle could be formed by hepatic metabolism, or as a result of transformation by gut bacteria. Other possible mechanisms of action include immunomodulation or interference with the invasion of new red blood cells by parasites, which can be species specific. Therefore studies in human subjects, as well as the observance of ethnomedical detailed data, are urged in order to exclude or confirm the activity of herbs traditionally used to treat malaria.
References
- 1. Emerging drug-resistance and guidelines for treatment of malariaJ Coll Physicians Surg Pak200414319324[PubMed][Google Scholar]
- 2. Malaria at the turn from the 2nd to the 3rd milleniumWien Klin Wochenschr200311529[PubMed][Google Scholar]
- 3. The behavioural and social aspects of malaria and its controlSpecial Programme for Research & Training in Tropical Diseases (TDR)2003Geneva: UNDP/World Bank/WHO125279–90[Google Scholar]
- 4. Ethnopharmacology and drug developmentCiba Found Symp19941854251discussion 51–59[PubMed][Google Scholar]
- 5. Epidemic malaria in the highlands of Papua New GuineaAm J Trop Med Hyg200572554560[PubMed][Google Scholar]
- 6. The search for new antimalarial drugs from plants used to treat fever and malaria or plants randomly selected: a reviewMem Inst Oswaldo Cruz20019610331042[PubMed][Google Scholar]
- 7. The Missouri Botanical Garden's VAST
- 8. International Plant Names Index
- 9. New York Botanical Garden vascular plants database
- 10. Brazilian's Northeast Plants Database
- 11. Antiplasmodial activities of some Ghanaian plants traditionally used for fever/malaria treatment and of some alkaloids isolated from Pleiocarpa mutica; in vivo antimalarial activity of pleiocarpineJ Ethnopharmacol20017699103[PubMed][Google Scholar]
- 12. Evaluation of French Guiana traditional antimalarial remediesJ Ethnopharmacol2005984554[PubMed][Google Scholar]
- 13. A search for natural bioactive compounds in Bolivia through a multidisciplinary approach. Part VI. Evaluation of the antimalarial activity of plants used by Isoceno-Guarani IndiansJ Ethnopharmacol200493269277[PubMed][Google Scholar]
- 14. Conquering the intolerable burden of malaria: what's new, what's needed: a summaryAm J Trop Med Hyg200471115[PubMed][Google Scholar]
- 15. Burchellin: effects on Triatoma infestans and on Trypanosoma cruzi within this vectorParasitol Res200187730735[PubMed][Google Scholar]
- 16. Antimalarial activity of crude extracts from Brazilian plants studied in vivo in Plasmodium berghei-infected mice and in vitro against Plasmodium falciparum in cultureBraz J Med Biol Res19912411131123[PubMed][Google Scholar]
- 17. Antimalarial activity of medicinal plants used in traditional medicine in S. Tome and Principe islandsJ Ethnopharmacol2002812329[PubMed][Google Scholar]
- 18. Synthesis and biological evaluation with plant cells of new fosmidomycin analogues containing a benzoxazolone or oxazolopyridinone ringJ Enzyme Inhib Med Chem200419559565[PubMed][Google Scholar]
- 19. The co-evolution of people, plants, and parasites: biological and cultural adaptations to malariaProc Nutr Soc200362311317[PubMed][Google Scholar]
- 20. The global distribution and population at risk of malaria: past, present, and futureLancet Infect Dis20044327336[PubMed][Google Scholar]
- 21. Plants against malaria. Part 1: Cinchona or the Peruvian barkJ R Coll Physicians Edinb200232189196[PubMed][Google Scholar]
- 22. Antimalarial activity of tropical Meliaceae extracts and gedunin derivativesJ Nat Prod199760336341[PubMed][Google Scholar]
- 23. Plants for Malaria; Plants for Fever1997Kew: Royal Botanic Gardens
- 24. In vitro antiplasmodial activity of some plants used in Kisii, Kenya against malaria and their chloroquine potentiation effectsJ Ethnopharmacol200384235239[PubMed][Google Scholar]
- 25. Plants traditionally prescribed to treat tazo (malaria) in the eastern region of MadagascarMalar J2003225[PubMed][Google Scholar]
- 26. Medicinal plants used to treat malaria in MadagascarJ Ethnopharmacol199237117127[PubMed][Google Scholar]
- 27. Pharmacokinetic study of artemisinin after oral intake of a traditional preparation of Artemisia annua L. (annual wormwood)Am J Trop Med Hyg200470128132[PubMed][Google Scholar]
- 28. Ethnobotanical survey and in vitro antiplasmodial activity of plants used in traditional medicine in Burkina FasoJ Ethnopharmacol200386143147[PubMed][Google Scholar]
- 29. A type II pathway for fatty acid biosynthesis presents drug targets in Plasmodium falciparumAntimicrob Agents Chemother200347297301[PubMed][Google Scholar]
- 30. Antiprotozoal activities of Colombian plantsJ Ethnopharmacol200178193200[PubMed][Google Scholar]
- 31. In vitro antiplasmodial activity and cytotoxicity of 33 West African plants used for treatment of malariaJ Ethnopharmacol200598281285[PubMed][Google Scholar]
- 34. Antiplasmodial activity of alkaloid extracts from Pavetta crassipes (K. Schum) and Acanthospermum hispidum (DC), two plants used in traditional medicine in Burkina FasoParasitol Res200390314317[PubMed][Google Scholar]
- 37. Fitoterapia e Medicina Científica1953Rio de Janeiro: Laboratório Flora Medicinal
- 38. A Malaria e Suas Diversas Modalidades Clínicas1885Rio de Janeiro: Lombaerts & Co
- 39. Antimalarial activity of Bidens pilosa L. (Asteraceae) ethanol extracts from wild plants collected in various localities or plants cultivated in humus soilPhytother Res200418634639[PubMed][Google Scholar]
- 41. História das Plantas Medicinais e Úteis do Brasil1853Rio de Janeiro: Companhia Typographica do Brasil
- 46. Indole and beta-carboline alkaloids from Geissospermum sericeumJ Nat Prod2002658588[PubMed][Google Scholar]
- 47. Elementos de Botânica Médica1877Rio de Janeiro: Typographia Nacional
- 54. In vivo antimalarial activities of Quassia amara and Quassia undulata plant extracts in miceJ Ethnopharmacol199967321325[PubMed][Google Scholar]
- 55. Antimalarial activity of Cinchona-like plants used to treat fever and malaria in BrazilJ Ethnopharmacol200387253256[PubMed][Google Scholar]
- 56. Antimalarial activity of cedroninJ Ethnopharmacol1994435761[PubMed][Google Scholar]
- 57. In vitro antiplasmodial activity of Central American medicinal plantsTrop Med Int Health19994611615[PubMed][Google Scholar]
- 58. Evolution and spread of antibiotic resistanceJ Intern Med200225291106[PubMed][Google Scholar]
- 59. Trans stimulation provides evidence for a drug efflux carrier as the mechanism of chloroquine resistance in Plasmodium falciparumBiochemistry20034293839394[PubMed][Google Scholar]
- 60. The current and future impact of antimicrobial resistance among nosocomial bacterial pathogensDiagn Microbiol Infect Dis1992153S10S[PubMed][Google Scholar]
- 61. Solvent tolerance in bacteria: role of efflux pumps and cross-resistance with antibioticsInt J Antimicrob Agents200322211216[PubMed][Google Scholar]
- 62. Defective DNA repair as a potential mechanism for the rapid development of drug resistance in Plasmodium falciparumBiochemistry20044348854891[PubMed][Google Scholar]