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Revista Brasileira de Farmacognosia

Print version ISSN 0102-695XOn-line version ISSN 1981-528X

Rev. bras. farmacogn. vol.16  suppl.0 João Pessoa Dec. 2006 



Plants and chemical constituents with giardicidal activity


Plantas e constituintes químicos com atividade giardicida



Flavia M.M. AmaralI,*; Maria Nilce S. RibeiroI; José M. Barbosa-FilhoII; Aramys S. ReisIII; Flávia R.F. NascimentoIII; Rui O. MacedoII

IDepartamento de Farmácia, Universidade Federal do Maranhão, Campus do Bacanga, Av. dos Portugueses s/n, Prédio da Farmácia, 65085-580, São Luís, Maranhão, Brazil
IILaboratório de Tecnologia Farmacêutica "Delby Fernandes de Medeiros", Universidade Federal da Paraíba, Caixa Postal 5009, 58051-970, João Pessoa, Paraíba, Brazil
IIILaboratório de Imunofisiologia, Universidade Federal do Maranhão, Campus do Bacanga, Av. dos Portugueses s/n, Prédio do Integrado, 65085-580, São Luís, Maranhão, Brazil




Intestinal infection caused by Giardia lamblia represents a serious public health problem, with increased rates of prevalence in numerous countries. Increased resistance of the parasite and the side-effects of the reference drugs employed in the treatment of giardiasis make necessary to seek new therapeutic agents. Natural products, especially of plant origin, represent excellent starting point for research. The objective of this study is to review the literature on plant extracts, fractions and chemical constituents whose giardicidal activity has been investigated in vitro. The review describes 153 (one hundred and fifty-three) plant species from 69 (sixty-nine) families that were evaluated for their giardicidal activity. The geographical distribution of the plant species, the part used, preparation, strain of Giardia lamblia tested and the results obtained by the authors are also given. One hundred and one compounds isolated from plant species, classified by chemical class, are presented. Recent aspects of research on natural products of plant origin employed in the treatment of giardiasis are also discussed.

Keywords: Giardia lamblia, giardicidal activity, natural products, medicinal plants, review.


Infecção intestinal causada por Giardia lamblia representa grave problema de saúde pública, com elevadas taxas de prevalência em diversos países. O aumento de resistência do parasita e os efeitos colaterais dos fármacos de referência empregados no tratamento da giardíase, tornam necessário a busca de novos agentes terapêuticos. Produtos naturais, especialmente de origem vegetal, representam excelentes fontes de pesquisas. Este trabalho tem como objetivo revisar a literatura de extratos de plantas, frações e compostos químicos com estudos in vitro de avaliação da atividade giardicida. A revisão refere 153 (cento e cinqüenta e três) espécies vegetais de 69 (sessenta e nove) famílias que foram submetidas à avaliação da atividade giardicida. Descreve a distribuição geográfica das espécies vegetais, parte usada, preparação, cepa de Giardia lamblia testada e resultados por autores. Apresenta 101 (cento e um) compostos isolados de espécies vegetais classificados por classes químicas. Discute aspectos recentes da pesquisa de produtos naturais de origem vegetal empregados no tratamento da giardíase.

Unitermos: Giardia lamblia, atividade giardicida, produtos naturais, plantas medicinais, revisão.




Giardiasis is an intestinal infection caused by the flagellate protozoan Giardia lamblia (syn: Giardia intestinalis, Giardia duodenalis) with a broad, worldwide distribution and high rates of prevalence (Thompson et al., 2000; Adam, 2001; Sogayar; Guimarães, 2003). According to the World Health Organization, the worldwide incidence is around 500,000 new cases per year (WHO, 1998). In developed countries, including the United States and Canada, Giardia lamblia is the intestinal parasite most commonly associated with outbreaks of diarrhoea (Ortega; Adam, 1997; Tessier; Davies, 1999). In developing countries the average prevalence is 20% among the general population (Ortega; Adam, 1997; Rocha, 2003). In Brazil, some epidemiological studies have registered levels of up to 63.3%, thereby constituting a serious public health problem (Cury et al., 1994; Guimarães; Sogayar, 1995; Newman et al., 2001).

During its evolutionary cycle Giardia lamblia presents in both cyst and trophozoital forms. The parasite is transmitted by faecal-oral contamination, through the ingestion of mature cysts present in untreated or inadequately treated water and contaminated foods. Direct person-to-person transmission through contaminated hands is common, mainly in group situations and among family members. There have also been reports of transmission through anal sex. However, contamination of humans through contact with infected animals is controversial (Adam, 1991; Flanagan, 1992; Nuñez et al., 2003; Rocha, 2003; Sogayar; Guimarães, 2003).

Giardia lamblia infection mainly affects children aged between 0 and 5 years, without distinction of sex, while the number of cases registered is significantly increased among homosexual men and immunocompromised individuals (Adam, 1991; Lebwohl et al., 2003; Sawangjaroen et al., 2005). Among Brazilian patients with acquired immunodeficiency syndrome, Giardia lamblia is the most frequent parasite related to intestinal diseases (Cimerman et al., 1999).

The majority of the hosts of Giardia lamblia is asymptomatic and plays an important role in the epidemiological chain, since, despite the absence of symptoms, they eliminate cysts, contributing significantly to the transmission of the disease (Tessier; Davies, 1999; Rey, 2001).

The clinical manifestations of giardiasis are varied, with diarrhoea being the predominant symptom, occurring in 90% of symptomatic patients. Diarrhoea may be acute and self-limiting or chronic and debilitating, associated with abdominal pain, flatulence, dyspepsia, epigastric pain, nausea, vomiting, and steatorrhea, malabsorption of fats and fat soluble vitamins and weight loss. The malabsorption of fats, carbohydrates, iron and vitamins (A and B12) retards physical and intellectual development, mainly among younger age groups (Farthing et al., 1986; Heresi et al., 2000; Gendrel et al., 2003; Lebwohl et al., 2003; Al-Mekhlafi et al., 2005).

The treatment of giardiasis consists of the use of one or more drugs, with metronidazole being the first choice. Other nitroimidazolic derivatives (secnidazole, tinidazole, and ornidazole), benzimidazoles (albendazole, mebendazole), furazolin, quinacrine and paromomycin have also been employed in therapeutic regimens. However, these drugs have adverse effects including gastrointestinal disturbances, nausea, headache, leucopoenia and an unpleasant taste in the mouth. Furthermore, they can lead to neurotoxic effects, ataxia, convulsions and vertigo, bringing about the interruption of treatment. In addition, mutagenic and carcinogenic effects have been described in laboratory animals (Morgan et al., 1993; Heresi et al., 2000; Harris et al., 2001; Campanati; Monteiro-Leal, 2002; Petri-Jr., 2003).

Bearing in mind the side effects of the reference drugs and the increased resistance of the parasite to conventional treatment, it has become necessary to seek new, safe and effective agents for the treatment of the infection (Harris et al., 2001; Sousa; Silva, 2001; Upcroft; Upcroft, 2001; Sangster et al., 2002).

Plants represent an important source of drugs, considering the wide diversity of molecules with medicinal potential, and can make an effective contribution to the search of new bioactive products, semi-synthetic medicines or lead compounds for the synthesis of medicines (Cowan, 1999; Yunes; Calixto, 2001; Pinto et al., 2002; Anthony et al., 2005; Gilani; Rahman, 2005). The exploitation of this potential source of medicine requires the bringing together of ethnobotanical, ethnopharmacological, chemical, biological, pharmacological and toxicological studies (Gilani; Rahman, 2005; Gurib-Fakim, 2006).

In the search for new active products of plant origin, literature reviews concerning plant extracts, semi-purified fractions and chemically defined molecules with biological activity have furnished important additional details, making an effective contribution to the definition of inclusion and/or exclusion criteria in the selection of plant species for the development of validation studies (Almeida et al., 2001; Sharma; Sharma, 2001; Pereira et al., 2002; Moura et al., 2002; Morais et al., 2003; Silva et al., 2003; Rocha et al., 2005; Falcão et al., 2005; Barbosa-Filho et al., 2005; 2006a,b; Funke; Melzig, 2006).

With the aim of contributing to the search for new alternatives for the control of Giardia lamblia infection, the present work reviews the literature of studies examining in vitro giardicidal activity carried out with extracts, fractions and chemical substances of plant origin.



This review covered Biological Abstracts, Chemical Abstracts, Medline, Web of Science, Lilacs and the data base of the University of Illinois-Chicago NAPRALERT (acronym for NAtural PRoducts ALERT), updated to June 2006. The references obtained in the review were consulted and analysed in details.

The key words employed in the literature review were Giardia lamblia x antigiardial activity x giardicidal activity x anti-protozoan activity x medicinal plants x natural products x natural compounds x in vitro x plant extracts.



Following the proposed methodology, the study resulted in the elaboration of tables of extracts, fractions and pure chemical compounds that have been evaluated for their in vitro giardicidal activity (Tables 1 and 2).

The efficacy of the biological activity of plant materials under analysis can be related to the location and time of collection, the part of the plant used, preparation of the plant material, strain of Giardia lamblia tested and the assay employed. Such factors justify the development of studies with the same plant species, but obtained from different localities and/or at different times of collection, to investigate the giardicidal activity with different strains of the parasite, methodology and/or by diverse authors.

Review of the literature showed that the in vitro giardicidal activity had been investigated in 153 plant species, distributed among 69 (sixty-nine) families, including a notable representation of Asteraceae, Fabaceae, Rutaceae and Verbenaceae with 25, 10, 7 and 6 species studied, respectively.

Based on the results of the in vitro biological assessment according to the concentration of the extracts and fractions tested, we established criteria for the classification of giardicidal activity as highly active (IC50 < 100 mg/mL), active (100 < IC50 < 250 mg/mL), moderately active (250 < IC50 < 500 mg/mL) and inactive (IC50 > 500 mg/mL). The studies which did not give the concentration of the extracts and/or fractions analysed for IC50, IC90, and IC100 values and/or MIC, giardicidal activity were classified according to the criteria of efficacy (active or inactive) defined by the authors. Table 2 presents the results for giardicidal activity based on the criteria of efficacy and/or IC50 values established by the authors cited.

Giardicidal activity of plant extracts and fractions

Ethnobotanical and ethnopharmacological studies have shown the wide use of plant species in the treatment of gastrointestinal disturbances, such as diarrhoea and dysentery (Ivancheva; Stantcheva, 2000; Singh et al., 2002; El-Hilaly et al., 2003; Alanís et al., 2005; Gilani et al., 2005; Velázquez et al., 2006), which are the frequent manifestations of infection with Giardia lamblia.

The popular use of plants in the treatment of intestinal parasitoses, especially giardiasis, together with the side effects of the reference drugs and the increase in the parasite resistance, has prompted the investigation of natural products, with a view to validate the giardicidal property attributed empirically, and raise the possibility of new alternative therapies.

One of the pioneering studies on plant species with giardicidal activity was carried out in Africa by Johns et al. (1995). The authors investigated the giardicidal activity of 36 (thirty-six) plant species employed in the treatment of gastrointestinal disturbances by the population of the Luo region, in East Africa. The results showed that 21 (twenty-one) methanolic extracts obtained from the species studied brought about death or growth inhibition in trophozoites of Giardia lamblia. Table 1 presents the results for giardicidal activity, classified as active or inactive according to the criteria adopted by the authors, considering that the concentration of extracts and fractions tested was not related to the IC50, IC90, IC100 and/or MIC values.

Studies carried out with plant species from Cuba by Ordõnez et al. (2001) and from the USA by McAllister et al. (2001) demonstrated significant activity of Artemisia absinthium (IC50: 200 mg/mL) and Yucca schidigera (IC50 : 15 - 250 mg/mL), respectively.

Recently, Sawangjaroen et al. (2005) reported that in Thailand patients infected with HIV and Giardia lamblia are known to self-medicate with plant species to treat giardiasis. The authors found that among the 12 (twelve) species tested, only 6 (six) exhibited significant giardicidal activity, with the most notable result being the efficacy of the chloroform extract of Alpinia galanga (IC50: 37.73 mg/mL).

Aside from the scarce investigation of the giardicidal activity of extracts and fractions carried out in Africa, Brazil, China, Cuba, India, USA, Malaysia, Venezuela and Thailand, the largest contribution to this area of study has come from Mexico, where numerous plant species are used in popular medicine for the treatment of gastrointestinal illnesses, which has in turn stimulated validation studies (Calzada et al., 1998b; 1999b; 2005; 2006; Ponce-Macotela et al., 2001; Tapia-Pérez et al., 2003; Peraza-Sánchez et al., 2005).

A biological investigation reported by Ponce-Macotela et al. (1994), involving 14 (fourteen) plants used in Mexico for the treatment of diarrhoea and/or parasitic infections, demonstrated a percent inhibition of the growth of axenic strains of Giardia lamblia in excess of 50% for the extracts of Castela tortuosa, Haematoxylon campechianum, Mangifera indica, Cupressus sempervirens, Punica granatum, Psidium guajava, Plantago major, Justicia spicigera and Lippia spp. The criteria for efficacy (active or inactive) defined by the authors are expressed in the results presented in Table 1.

A study involving Althernanthera repens, Boerhavia coccinea, Flavenia trinerva, Leucaena esculenta, Tradescantia zebrina, Tournefortia densiflora, Vitex mollis and Waltheria americana; plant species used in traditional medicine in Mexico for the treatment of gastrointestinal disturbances, demonstrated that all of these species, except Tradescantia zebrina, possessed giardicidal activity at concentrations less than or equal to 100 mg/mL, with the greatest effect being found in assays with extracts of the Tournefortia densiflora seeds (Tapia-Pérez et al., 2003).

In an assessment of the giardicidal activity of extracts and fractions obtained from 6 (six) plant species used by the population of Southern Mexico, Calzada et al. (1998a) found a greater efficacy of Rubus coriifolius, Cuphea pinetorum and Helianthemum glomeratum, with IC50 values of less than 100 mg/mL.

Calzada et al. (1998b) reported a study carried out with the methanolic extracts of 19 (nineteen) plant species of Mexican origin, distributed among 13 (thirteen) families, and described potent giardicidal activity in 6 (six) species (Acalypha phleoides, Cnidoscolus tehuacanensis, Geranium nievum, Hellianthella quinquenervis, Heliopsis longipes and Teloxys graveolens), with IC50 values less than or equal to 20.64 mg/mL.

Plant species selected for an ethnobotanical project, carried out in conjunction with Maya communities of the Yucatan peninsula (Mexico), were extracted with polar and non-polar solvents and tested for giardicidal activity, with the results showing that all the species returned IC50 values of below 90 mg/mL (Ankli et al., 2002). In addition, the methanolic extracts obtained from all 10 (ten) plant species tested which are native to the Yucatan peninsula (Mexico) exhibited giardicidal activity, with IC50 values between 6.34 and 117.41 mg/mL; the most active species was Tridax procumbens (Peraza- Sánchez et al., 2005).

A recent investigation involving methanolic extracts of 26 (twenty-six) Mexican plant species found that 20 (twenty) possessed intense giardicidal activity, with IC50 values below 100 mg/mL, while Dorstenia contrajerva was the most activite with an IC50 of 23.3 mg/mL (Calzada et al., 2006).

In Brazil, there have been very few studies so far aimed at validating extracts and fractions with giardicidal activity. In the process of preparing this review, only 2 (two) studies were identified, carried out in Rio de Janeiro, which validated the use of Hovenia dulcis (IC50 value: 12 mg/mL for the dichloromethane fraction) (Gadelha et al., 2005) and Mentha x piperita (IC50 values: 0.8; 2.5 and 9.0 mg/mL for the methanolic, dichloromethane and hexanic extracts, respectively) (Vidal et al., 2007).

According to the data presented in Table 1, it can be concluded that 117 (one hundred and seventeen) plant species, belonging mainly to the Asteraceae, Fabaceae, Rutaceae and Verbenaceae families exhibit in vitro giardicidal activity, classified as strongly active and active.

There is a great diversity of flora in Brazil which is mainly concentrated in the pre-Amazon region. There is also a tradition of usage of plants for therapeutic ends in this country. The high rate of intestinal parasitoses, mainly due to Giardia lamblia found in the Brazilian population is a motivation for studies on the giardicidal activity of plant species which are popular and in widespread use in Brazil. Therefore, much emphasis should be given in this line of research, with a view to contributing to alternatives based on natural products to combat this disease.

Giardicidal activity of chemically defined molecules

The literature review identified 101 (one hundred and one) chemical substances isolated from diverse plant species submitted to biological study for the assessment of in vitro giardicidal activity. The active compounds isolated and identified belonged to the classes of flavonoids (40), especially flavanols and isoflavones, as well as triterpenes (28), with the quassinoids being the most representative, alkaloids (18), mainly indole alkaloids, sesquiterpenes (04), steroids (04), phenolic acids and esters (03), lignan (01) and amine (01). These are presented in Table 2 in alphabetical order of their chemical names, followed by the class, plant species of origin, strain tested, results and references.

The data presented in Table 2 show that diverse flavonoids isolated from different plant species exhibited giardicidal activity demonstrated in the in vitro assay of cytotoxicity against trophozoites of Giardia lamblia, with IC50 values varying between 0.03 and 178.7 mg/mL. Formononetin, an isoflavone isolated from Dalbergia frutescens, exhibited intense activity with an IC50 below that of metronidazoleÒ, the reference drug for the giardiasis treatment and employed as a positive control in the assays (Khan et al., 2000). Eleven compounds, including flavonoids, steroids and triterpenes were isolated from the genus Geranium, represented by the species Geranium mexicanum and Geranium niveum (Calzada et al., 1999a; 2001b; 2005).

Bruceantin, (-)-epicatechin, b-sitosterol, b-sitosterol 3-O-b-D-glucopyranoside, hyperin, kaempferol, narcissin, quercetin and rutin are examples of compounds isolated from distinct plant species whose activity has been examined in vitro against different strains of Giardia lamblia by various authors (Gillin et al., 1982; Wright et al., 1993a; Calzada et al., 1999a; 1999b; 2001a; 2003; 2005; Calzada 2005; Arrieta et al., 2001; Alanís et al., 2003).

The great variety of chemical classes under study is indicative of diverse mechanisms of action involved in the lysis and death of Giardia lamblia cells, reinforcing the necessity for the development of complementary studies for the evaluation of the selectivity of the cytotoxicity of the compounds.



This literature review shows that the majority of extracts and fractions obtained from plant species employed in popular medicine for the treatment of diarrhoea and dysentery exhibit in vitro giardicidal activity, and these are mainly from species belonging to the Asteraceae, Fabaceae, Rutaceae and Verbenaceae families. These studies need further confirmation. The active compounds encountered so far may lead to the discovery of new drugs to combat this disiase.



The authors are grateful to the University of Illinois, Chicago, USA for permission to consult NAPRALERT, to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) through the Programa de Qualificação Institucional (PQI) and to the Conselho Nacional de Pesquisa (CNPq) for financial support.



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Received 03/28/06
Accepted 09/19/06



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