Acanthospermum hispidum DC (Asteraceae): perspectives for a phytotherapeutic product

Acanthospermum hispidum DC (Asteraceae): perspectivas para um produto fitoterápico

REVISÃO

Acanthospermum hispidum DC (Asteraceae): perspectives for a phytotherapeutic product

Acanthospermum hispidum DC (Asteraceae): perspectivas para um produto fitoterápico

Evani de L. Araújo^{I, *}; Karina P. Randau^I; José G. Sena-Filho^I; Rejane M. Mendonça Pimentel^II; Haroudo S. Xavier^I

^ILaboratório de Farmacognosia, Departmento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Av. Prof. Arthur de Sá s/n, Cidade Universitária, 50740-521 Recife-PE, Brazil

^IILaboratório de Fitomorfologia, Departamento de Biologia, Universidade Federal Rural de Pernambuco, Av. Manoel de Medeiros, s/n, Dois Irmãos, 52171-900 Recife-PE, Brazil

ABSTRACT

The "Espinho-de-cigano" plant (Acanthospermum hispidum DC) is used throughout northeastern (NE) Brazil as a folk medicine for asthma. Although little is actually known about the effectiveness and safety of this plant extract product, it is possible to find numerous medicines prepared from it in public health services or in stores selling natural products. This study aimed to undertake a literature review relative to Acanthospermum hispidum covering the period between 1926-2006 within the areas of ethnobotany, phytochemistry and pharmacology. The objective was to contribute to a better knowledge of this species and its uses, as well as to aid in improving its performance as a natural medicine. The species is easily identifiable and grows abundantly during the rainy seasons in NE Brazil; is amenable to cultivation without lose of its phytochemical profile, and toxicological studies have showed its safety as a medicine (although more studies will be required in that direction). As such, the compilation of the accumulated knowledge concerning this species will aid in evaluating its pharmacological value, guaranteeing quality control of the final product, and in preparing recommendations for usages and dosages that offer both safety and efficiency to the user.

Keywords: Acanthospermum, Asteraceae, medicinal plants, phytochemistry, asthma.

RESUMO

A planta "Espinho-de-cigano" (Acanthospermum hispidum DC) é amplamente usada no nordeste do Brasil como medicamento popular para a asma. Embora muito pouco seja conhecido atualmente sobre a eficácia e segurança deste extrato vegetal, é possível encontrar numerosos medicamentos preparados com ele nos serviços públicos ou em lojas que vendem produtos naturais. Este estudo visa proceder a uma revisão de literatura relativa à A. hispidum, no período entre 1926-2006, nas áreas de etnobotânica, fitoquímica e farmacologia. O objetivo foi contribuir para um melhor conhecimento desta espécie e seus usos, assim como auxiliar na melhora de seu desempenho como um medicamento natural. A espécie é facilmente identificável e cresce abundantemente durante a estação chuvosa no nordeste do Brasil; é possível cultivá-la sem perda de seu perfil fitoquímico e os estudos toxicológicos têm mostrado sua segurança como um medicamento (embora mais estudos sejam requeridos nestes aspectos). Assim sendo, a compilação do conhecimento acumulado relativo a esta espécie auxiliará na avaliação de seu valor farmacológico, garantindo o controle de qualidade do produto final, e no preparo das recomendações para usos e dosagens que ofereçam segurança e eficiência ao usuário.

Unitermos: Acanthospermum, Asteraceae, plantas medicinais, fitoquímica, asma.

INTRODUCTION

Acanthospermum hispidum, popularly known as "Espinho-de-cigano" ("Gypsy-Thorn"), has been traditionally used in northeastern Brazil for treating asthma, bronchitis, fevers and as expectorant, as vermifuge and against intestinal pains (Morais et al., 2005; Tôrres et al., 2005; Agra et al., 2007; 2008). Recent public health programs showed the results obtained in treating bronco-asthmatic problems with syrups prepared from this plant have raised awareness about this folk medicine and has provoked a significant increased in demand for this product. It is also possible to find extracts of this plant in stores specializing in natural products and natural medicines, although these preparations often do not meet even the minimal requirements the National Health Service Agency Anvisa (2000), in terms of their quality control, proof of efficiency, or safety (Araújo et al., 2002). Even recognizing the normal difficulties involved in working with folk remedies and products of extensive popular usage, a lack of research and control may expose patients to an inefficient use of such a product or even health risks.

It is well known that commercial marketing of any medicine extends from the initial identification of a potentially useful species through the long processes and high costs of intensive research on the quality, safety and efficiency (although this process is often more efficient when natural products are involved, in contrast to purely synthetic compounds). There has been a tendency throughout the world for increasing demands for phytotherapeutic compounds, stimulating the interest of large laboratories in finding more of these "new" drugs. But in spite of the growth of the pharmaceutical industry, significant numbers of people still depend on home remedies and self-medication, creating a need and an interest in reorganizing the cultural and scientific knowledge concerning popularly used plants - the goal of the present work.

MATERIAL AND METHODS

An extensive bibliographic search was undertaken to identify works on medicinal plants published in periodicals, data banks, and rare or current texts stored in public and private libraries during the period between 1926 and 2006, including sources such as NAPRALERT - Natural Products Alert, the data bank of the University of Illinois, Chicago; Chemical Abstracts; ICBN - International Code of Botanical Nomenclature; FDA - Food & Drugs Administration (USA), the on-line periodical bank of the Coordination for Improvement of Graduate Level Personnel (CAPES), and similar sources. Additionally, we consulted published monographs, thesis, and proceedings of scientific congresses, websites, and technical research publications, as well as production protocols of the Laboratory of Phytotherapy of the Municipality of Olinda, Pernambuco State, Brazil where plant extracts of Acanthospermum hispidum have been produced and utilized for more than ten years as a main component of phytoterapic product.

RESULTS AND DISCUSSION

Botanical investigations

The specie name of Acanthospermum hispidum was derived from the Greek words ákanthos and sperma, which mean "thorn" and "seed", respectively (Cunha, 1982); while hispidum is derived from Latin, meaning "rough" (referring to the rough hairs covering the seed) (Saraiva, 2000). Also, the name describes a hirsute species with seeds protected by hairs and thorns.

The family Asteraceae (Dumortier 1822 nom. conserv.) is known in older texts as the Compositae. It is the largest angiosperm family (Cronquist, 1981; Barroso et al., 1991; Verdi et al., 2005), containing more than 1,500 genera comprising approximately 25,000 known species (ICBN, 2005; Verdi et al., 2005) and represents nearly 10% of the world's total flora (Bremer, 1994). Although about 98% of the Asteraceae are small plants, the family also includes subshrubs, vines, a few trees, and even some aquatic species. The principal defining characteristic of this family is the presence of numerous flowers united in a capitulum (Joly, 1978).

The genus Acanthospermum (Schrank. Pl. Rar. Hort. Monac. 53, 1819) (Aranha et al., 1972) comprises annual herbaceous plants that are either erect or prostrate. The leaves are simple, opposite, with serrate or entire margins, and the inflorescence is axial or terminal, with yellow flowers. The fruit is an achene, oblong, with rigid and persistent hairs. The principal species composing this genus are: australe (Loefl.) Kuntze, 1891; brachyceratum S.F. Blake, 1922; brasilum (Schrank, 1822); donii (S.F.) Blake, 1921; glabratum (DC.) Wild, 1967; hirsutum DC., 1836; hispidum DC., 1836; hispidum A. Chev., 1920; humile (Sw.) DC. 1836; humile var. hispidum (DC.) Kuntze, 1891; humile var. hispidum Kuntze, 1891; lecocarpoides B.L. Rob. & Greenm., 1895; leptolobum S.F. Blake, 1922; microcarpum B.L. Rob., 1902; simile S.F. Blake, 1921; xanthioides (Kunth) DC., 1836; xanthioides var. acutifolium; xanthioides var. glabratum DC., 1836; and xanthioides var. obtusifolium DC., 1836. The species australe and hispidum have economic importance in Brazil, as they are invasive weeds in agricultural fields. They are denominated in many regions with the same popular name and are often considered to have the same medicinal uses (Lorenzi & Matos, 2002).

Cronquist (1981) observed that phytochemical modifications may have been even more important than morphological changes in terms of the evolutionary success of this family, as exemplified by the utilization of polyacetylenes and sesquiterpenoid lactones to repel predators that have adapted to the iridoids produced by the older members of these taxa.

In the specific case of the species A. hispidum (DC. Prodr. 5:522, 1836) (Aranha et al., 1972), Stuessy reviewed the sub-tribe Melampodiinae, to which this species belongs, on two occasions (in 1973 and in 1977); in the second revision this author redistributed the component genera (Seaman et al., 1980). In 1979, Bohlmann proposed the use of sesquiterpene lactones as taxonomic markers in the identification of the tribe Heliantheae. As such, sesquiterpenoid-lactones have an important taxonomic role in the Asteraceae, with more than 900 of these compounds already identified, some of them showing anti-helmintic, anti-parasitic, antibiotic, and anti-carcinogenic activities (Bruneton, 1991; Evans, 1996).

The species A. hispidum is an erect annual plant, reaching up to one meter in height, with stems and leaves that are densely pubescent. The root system is ramified, showing a principal root up to 20 cm long with innumerous secondary roots, and gives off a characteristic light, slightly sweet, aroma. The stem is covered with fine hairs, the leaves have a bitter taste, simple and opposite, and measuring on the average 6 x 3 cm. The flowers are axillary, arranged in capitula, with small yellow flowers. The fruits are achenes, long, with a triangular form, and covered with irregular hairs that lend the plant other popular names, including "carrapicho-de-carneiro" (sheep's-thistle) or "carrapicho-de-três-pontas" (three-pointed-thistle) (Aranha et al., 1972; Corrêa, 1926; Lorenzi, 1982; Coimbra, 1994).

Geographical and agricultural profile

Although A. hispidum is pantropical (Menut et al., 1995), the species is considered to have its origin in central and southern America (Braga, 1976). It occurs in Brazil from the state of Piauí south to Rio Grande do Sul (Braga, 1976; Corrêa, 1978). It was probably introduced from South America to both India (Nair et al., 1985) and Africa (Summerfield & Saalmullera, 1998), which may be one of the sources of the large number of popular names attributed to this plant. Due to its role as an invasive weedy species on agricultural lands it has been the subject of many publications in Brazil and other countries. A. hispidum can be found in the wheat fields in the state of Minas Gerais (Cunha et al., 1985; Brandão et al., 1986a) through urban coastal areas in the municipality of Rio de Janeiro (Brandão et al., 1986b), although it is less frequent in the northern and northwestern regions of the country. It occurs spontaneously and predominantly along the coast in the state of Pernambuco, having also been detected in numerous cities in the interior of that state (Tabarelli & Silva, 2002).

Although A. hispidum has long been principally considered an invasive weed of agricultural plantations, it has recently become sought after as raw material to manufacture syrup produced by public health services in a number of municipalities to treat asthma. A year-round demand for this plant has led to its cultivation, as it occurs spontaneously only during the rainy season.

Although is not very competitive when compared to other invasive weeds (Voll et al., 1997), A. hispidum has been shown to be resistant to a number of different types of herbicides (Reddy, 1965, Luo & Matsuomoto, 2002), and has showed an insecticidal activity against the larvae of a species of lady-bug (Epilachna varivestes) (Kraus et al., 1994).

In general, the seeds of A. hispidum remain dormant in the soil for periods of up to eight years, reappearing at each new preparation of the soil (Schwerzel & Thomas, 1979) according to the rainfall and temperature regime. Garcia (1992) examined seed dormancy and related it to climatic factors, noting that dormancy could be broken by incubation in the dark for 10-30 days.

Preliminary experiments undertaken by Messias & Noronha (1994) at the Pernambuco Agricultural Research Group (IPA) recommended fertilizing the soils used for cultivating this species with 15% urban compost, with additions of ammonia, phosphate and potassium (40-20-40).

Cultivated specimens of A. hispidum will germinate on a wide variety of soils, from sandy to clay. The transition from the flowering to the fruiting phase of this species is extremely rapid, demonstrating a metabolic priority of reproduction over the elaboration of chemical defenses (Miranda, 1996).

Phytochemistry

Asteraceae has been one of the most studied plant families, in large part due to the promising chemical compounds produced by this group. This research has lead to the development of pharmaceutical compounds, insecticides (such as piretro), and other products. In the specific case of A. hispidum, there is a huge volume of literature related to research on numerous chemical components extracted from this plant, as well as chemotaxonomic and phytotherapeutic investigations. The oldest phytochemical studies encountered dated to 1975, when Herz reported investigations concerning sesquiterpene lactones with potential biological activities, and to 1976, when Ramachandran et al., as well as Mathur & Bejarane, published further studies on A. hispidum. The sesquiterpene lactones found in A. hispidum are chemically distinct from other sesquiterpenoids due to the presence of an α-methylene-γ-lactone system, many containing carbonyl α,β-unsaturated and epoxies, which are part of a larger family of compounds with a wide spectrum of biological activity, including anti-microbial and anti-tumor activities (Robers, 1997). Using thin-layer chromatography, Xavier & Araújo (1998) studied samples of plants that were either cultivated or growing spontaneously, and found no qualitative differences in their phytochemical patterns. The use of these plants as forage by cattle during the dry season has drawn investigative interest because of the reported toxicity of the seeds (Cunha et al., 1985).

Investigations of other species of Acanthospermum have led to the isolation of cis-cis-germacranolides and melampolides. Additional compounds isolated from A. hispidum are listed in Table 1.

Uses

Many species imported by Europeans and Africans during the early colonization of Brazil became acclimatized and incorporated into the already rich plant heritage of the country. Likewise, many native plant species were carried to other regions, often in an involuntary manner. This was probably the case of Acanthospermum, whose seeds adhere to clothes or animal fur, and is now found in many different countries and even on other continents around the world.

The initial steps of an ethnological study usually focus on the synonymy of popular names (which can vary greatly depending on the region, as was observed in the present study), use, indications, appearance, etc. This information is presented in Table 2, together with bibliographic references and, when possible, the region or country of origin.

In addition to the many medical indications found for A. hispidum there are also variations on the plant part utilized. In India the seeds are ingested orally to treat bed wetting, while in Malaysia, the entire plant is mixed with castor oil and applied to the skin to treat scabies. Corrêa (1926) compiled a basic compendium of medicinal plants in Brazil, and described the use from the roots of A. hispidum to treat coughs and bronchitis, while noting that the seeds are toxic to chickens. Other authors have indicated the use of this plant for treating bronchial spasms (Braga, 1976; Lorenzi, 1982; Silva & Oliveira, 1994; Matos, 1997).

Although recognizing that the two species are distinct, Lorenzi & Matos (2002) attributed the same properties and the same popular names to both A. hispidum and A. australe. Barros & Napoleão (2003) also noted that these species were used in Afro-Brazilian religious ceremonies (candomblé). A collection of the indications encountered for A. hispidum are is listed in Table 3.

Pharmacology

Table 4 lists information relevant to the biological activity of A. hispidum as described in the literature.

Preliminary studies indicated that A. hispidum showed low toxicity (Araújo et al., 1989), information that was confirmed in later publications in which root extracts of this species were found to have neither bactericidal or mutagenic effects, nor did they show toxicity at doses up to 2g/kg in rats (Hussain et al., 1990). Studies by Bakhita & Adam (1978a,b), however, had showed the toxicity of ingested seeds in mice as a result of liver damage, glomerular atrophy, congestion and hemorrhaging in the spleen, the lungs and the heart, in addition to catarrhal enteritis (Bakhita & Adam, 1978a,b), as noted in Table 5. The observed toxicity of the seeds resulted in the classification of this plant as "restricted" by the Food and Drugs Administration - FDA (USA) (FDA 2005).

Due to its common occurrence, Acanthospermum hispidum is easy to identify and viable for cultivation.

The phytochemical profiles of cultivated plants did not show significant differences from those of spontaneous individuals, nor did this profile alter during growth and development, thus making it apt for harvesting after only short periods of growth.

In general, few biological or phytochemical studies have focused on the roots of Acanthospermum hispidum although they are extensively used in popular medicine throughout northeastern Brazil (although not commonly in other localities), pointing to the need for more research concerning this plant part.

On the other hand, tests of acute, sub-acute and chronic toxicity, together with pre-clinical trials of possible anti-asthmatic action, support the widespread and popular use of "Espinho-de-cigano". Better defined indications, contraindications and doses, as well as standardization of the raw material used in medicinal preparations and formulations would allow the product to advance more rapidly to the phase of clinical trials.

To that end, it will be important to gather more technical information concerning products derived from "Espinho-de-cigano" that will meet the standards of the National Health Service Agency (Anvisa). This type of information is available for only a very few native Brazilian species, neglecting many with well-established and traditional folk uses.

While large pharmaceutical industries tend to focus on research on "new" compounds with therapeutic potentials that can bring in short- to medium-term profits, in order to attend the necessities of developing countries where there are only limited public resources available for research, and the populations are more susceptible to illnesses and all of their consequences, it might be more efficient to restrict initial research to proving the efficiency of established folk remedies and to standardizing the quality and safety of plant extracts already widely used and approved by local populations.

CONCLUSION

This specie is easily identified and its occurrence is wide during the rainy periods, viable to domestic cultivation, without alterations in the phytochemical standard. This literature review evidenced the scarcity of studies about the roots; the sesquiterpene lactones in this organ showed be promissory as phytochemical markers to the quality control for the phytotherapics. In spite of the toxicity founded in seeds, the roots showed LD₅₀ i.p. = 2g.kg^-1 body weight, indicating safety to its use. The need of establishment of a dossier from the product, attending the exigencies of the current legislation, is evident and urgent, in consequence of the extensive commerce of different products for long years.

Received 29 September 2008

Accepted 4 November 2008

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Publication Dates

• Publication in this collection
  09 Mar 2009
• Date of issue
  Dec 2008

History

• Accepted
  04 Nov 2008
• Received
  29 Sept 2008