Astraea lobata ( L ) Klotzsch ( Euphorbiaceae ) : An ethnopharmacological review

This is a review on the medicinal uses, phytochemistry and biological activities of A. lobata with a view to present a better understanding of the medicinal potentials of the species. Published literature on A. lobata were sourced from databases such as Google Scholar, Web of Science, SciFinder, Scopus, Science Direct, PubMed, Scielo, Springerlink, Google Patents, Espacenet, BioMed Central (BMC) and Medline. Astraea lobata is native to north, central and south America, and now naturalized in Benin, Ghana, Ivory Coast, Nigeria, Senegal and Togo where it is used to treat numerous diseases including dysentery, malaria, menstrual problems, scorpion bite, rheumatism pain, skin cancer, sterility in women and as purgative. Multiple classes of phytochemicals such as alkaloids, anthraquinones, esters, diterpene alcohols, flavonoids, hydroxy ketones, peptides, phenolics, saponins, steroids, tannins, triterpenes and triglycerides have been isolated from fruits, leaves, roots and stems of A. lobata. Scientific studies on A. lobata indicate that it has a wide range of pharmacological activities which include antibacterial, antidiabetic, antiplasmodial, antioxidant, antitrypanosomal and leishmanicidal activities. The wide usage of A. lobata as a herbal medicine calls for detailed pharmacological and phytochemical studies aimed at correlating the documented medicinal uses of the species with its biological activities and phytochemistry.


INTRODUCTION
Astraea lobata (L.) Klotzsch (family Euphorbiaceae) is a member of Astraea Klotzsch genus.This is a monophyletic north, central and south American genus with only 10 species, and is considered as sister group to the genus Croton L., with which it shares many morphological features [1,2].In tropical Africa, A. lobata has been introduced in Benin, Cameroon, Eritrea, Ethiopia, Gambia, Ghana, Guinea-Bissau, Ivory Coast, Mali, Nigeria, Senegal, Sierra Leone, Somalia, South Sudan, Sudan and Togo [3].It is an invasive species occurring as a pioneer species in the first stage of vegetation establishment after land clearing in tropical Africa [3,4].The species is also found in fallows, open sandy localities, river banks, along roadsides, waste land and is regarded as an arable weed in farmlands and irrigated agricultural plots [4].The naturalized species is difficult to eradicate from arable agricultural fields because of its deep taproot system and strong lateral roots with some small scale farmers using herbicides to control the weed [3,4].It is sold in informal markets as both herbal medicine and leafy vegetable in Benin [4].
Astraea lobata is an annual, monoecious and herbaceous plant with hairy and dense branches.The plant is erect up to 1 m tall, sometimes woody at the base with a long taproot [3].The leaves are alternate, with small stipules and palmately 3-5 lobed.The lobes are oblanceolate to obovate in shape, apex acuminate with toothed margins, hairy stellate to almost glabrous on both sides in some cases.The inflorescence is a slender, axillary or terminal raceme; with small male flowers in the upper half and female flowers in lower half.The flowers are regular, unisexual, yellowish green in colour, male flowers with elliptical sepals and oblanceolate petals while female flowers have linearlanceolate sepals.
The fruit is a globular capsule, stellate hairy, green in colour with three ellipsoid seeds.It is listed by Schmelzer [3] and Neuwinger [5] as an important herbal medicine widely used to treat and manage several human diseases in tropical Africa.
It is against this background that this review was carried out aimed at evaluating the ethnobotany, phytochemistry and biological activities of A. lobata so as to highlight the knowledge gap and provide baseline data required for further research on the plant species.

METHOD
To identify relevant information on the botany, medicinal uses, phytochemistry and biological activities of A. lobata, a review was compiled based on scientific literature from various sources including Google Scholar, Web of Science, SciFinder, Scopus, Science Direct, PubMed, Scielo, Springerlink, Google Patents, Espacenet, BioMed Central (BMC) and Medline.The keywords used for identification of relevant data included different scientific name and synonyms, common English name, and the terms: biological activities, medicinal uses, ethnobotany, ethnopharmacology, medicinal, pharmacology, phytochemistry and therapeutic value, Astraea lobata, Croton lobatus L. and lobed croton.Other relevant scientific publications were obtained from the University of Fort Hare library, Alice campus in South Africa.

Ethnomedicinal uses of Astraea lobata
In Benin, Nigeria and Togo, the flower, fruit, leaf, root, seed or stem decoction of A. lobata is taken orally as remedy for malaria [6][7][8][9][10][11][12] while in Ghana and Nigeria, the leaf decoction is taken orally or applied topically as remedy for skin cancer [13,14] (Table 1).In Ivory Coast, Nigeria and Togo, the bark, fruit, leaf, root, seed or stem decoction is taken orally as a purgative [5,11,15] while in Nigeria and Togo, the flower, fruit, leaf, root, seed or stem decoction is taken orally as remedy for dysentery [6,10,11].In Benin and Nigeria, the flower, fruit, leaf, root or seed decoction of A. lobata is taken orally as remedy for fever [3,8,12,16] and in Ivory Coast and Nigeria, the bark, leaf or root decoction is taken orally as remedy for rheumatic pain [5,15,17,18].
In Ivory Coast and Togo, the leaf decoction of A. lobata is used as a lotion or enema as remedy for sterility in women [5] while in Nigeria and Saudi Arabia, the leaf decoction is applied topically as a scorpion sting antidote [17,19].In Nigeria and Senegal, the bark, leaf, root or seed decoction of A. lobata is taken orally as remedy for convulsions [5,15,20,21] and in Nigeria and Venezuela, a fruit decoction is taken orally as remedy for menstrual problems [22,23].In Benin, the penis is washed with leafy twig macerate of A. lobata as an aphrodisiac [3] and flower, leaf or root decoction is used as antispasmodic in cases of threatening miscarriage and hiccups [5,8,12].The leaf decoction of the species is mixed with honey and palm oil and applied topically on stiff limps [3].Astraea lobata is used to treat jaundice and are recommended to pregnant women for the welfare of the foetus in Benin [4].Leaves of A. lobata are mixed with those of Hildegardia barteri (Mast.)Kosterm.as remedy for hypertension [5] and mixed with Ipomoea mauritiana Jacq.as colic in children [24].In Nigeria, the bark, fruit, leaf, root, seed or stem decoction of A. lobata is used as remedy for body rash, diabetes, guinea worms, impetigo, lactation, measles, obesity, sickle cell anemia, skin diseases, stomach ache, ulcers, urinary disorders and wounds [5,11,[15][16][17][18]20,[25][26][27][28][29][30][31].
In Nigeria, the fruit decoction of A. lobata is taken orally mixed with Vernonia amygdalina Delile leaves and Macaranga barteri Mϋll.Arg.leaves as remedy for diabetes [32].In Senegal, leaf or whole plant is used as sterilizer or against mouth infections and whooping cough [5].In Togo, leaf juice is applied topically as remedy for eye problems and unconsciousness [5] and the flower, leaf or root decoction is taken orally for pregnancy problems [6,10].In Venezuela, A. lobata is used as haemocatharsis [22] and the entire plant is used as a hunting poison in the coastal interior of the Ivory Coast [5].

Chemical composition of Astraea lobata
Plant parts such as fruits, leaves, roots and stems are known to have nutritive and non-nutritive compounds (Tables 2 and 3) which may be used to explain the medicinal uses and pharmacological properties of the species.The reported compounds such as alkaloids, diterpene alcohol, ester, flavonoid, hydroxyl ketone, peptide, phenolic acid, steroid, Fruit decoction applied topically Nigeria [27] triglyceride and triterpene were identified and characterized by various criteria including high resolution electron impact mass spectrometry, (HREIMS), high-resolution electrospray ionisation mass spectrometry (HRESIMS), highresolution mass spectrometry (HRMS), infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR), thin-layer chromatography (TLC) and ultraviolet visible spectroscopy (UV).

Antibacterial activities
The antibacterial activities of methanol extracts of aerial parts of A. lobata against Enteroccocus feacalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were evaluated by Lagnika et al [36] using micro dilution method with gentamicin as a positive control.

Antidiabetic activities
The ameliorative effects of A. lobata on alloxaninduced diabetes and associated cardiovascular derangements were evaluated by Fasola et al [37] by assessing the effects of the leaf extract on blood glucose level, blood pressure changes, electrocardiographic (ECG) abnormalities, lipid profile, and anti-oxidant status of alloxan-induced diabetic rats.Acute toxicity studies revealed no mortality of rats at the administration of different doses of extract up to the 5,000 mg/kg dose.
Histology of the pancreas showed focal area of necrosis and fatty infiltration in diabetic untreated rats, but these lesions were absent in pancreas of rats treated with A. lobata extract.Methanol leaf extract of A. lobata reduced arteriogenic risk factors, improved antioxidant status, restored the observable pathological lesions associated with experimental diabetes in rats [37].
This study shows that A. lobata possesses blood glucose lowering effects, antihypertensive effect, as well as antioxidant and free radical scavenging properties.The exhibited antidiabetic activities validates the traditional use of the leaves, fruits, seeds and stems of A. lobata as herbal medicine against diabetes in Nigeria [11,32].Therefore, further investigation on the different phytochemical constituents may be beneficial for the treatment and management of diabetes mellitus and its complications, and provide a safer and cheaper alternative to the currently available anti-diabetic drugs.

Antioxidant activities
The antioxidant activities of methanol extracts of aerial parts of A. lobata were evaluated by Lagnika et al [36] using the 2, 2diphenylpicrylhydrazyl (DPPH) radical scavenging assay.The extract demonstrated radical scavenging activities with IC 50 value of 1.96 μg/ml [36].Similarly, Odukoya et al [27] evaluated antioxidant activities of ethanol extracts of A. lobata fruits using the DPPH radical scavenging assay and lipid peroxidation using the thiobarbituric acid reactivity method.The extract demonstrated antioxidant capacity of 46.0 ± 0.0 %.It was observed that as the concentration increased, the amount of thiobarbituric reactive substances values decreased indicating low levels of malondialdehyde and a reduction in lipid peroxides both in the raw and cooked homogenate of Scomber japonicum Houttuyn fish.Results obtained by Odukoya et al [27] showed that there are more reactive oxygen species being destroyed with increasing concentrations of extract.Lipid peroxidation is considered responsible for the impairment of endothelial cells, keratinocyte capillary permeability, fibroblast and collagen metabolism [27].Therefore, it can be concluded that the increased lipid peroxidation might be one of the factors causing the defect in vascular endothelial growth factor expression and finally producing the impairment in the wound-healing process.These antioxidant activities demonstrated by A. lobata extracts are probably due to flavonoids and phenolics that are common in the species [27,33] and also known to exhibit antioxidant activities [40].

Cytotoxicity and toxicity activities
The cytotoxicity activities of geranylgeraniol and betulinic acid isolated from the stems and leaves of A. lobata were evaluated by Attioua et al [39] on L6 murine myoblast cells.The compound geranylgeraniol showed good selectivity with an SI value (SI is ratio of cytotoxicity to biological activity) over 25.It is generally considered that biological efficacy is not due to in vitro cytotoxicity when SI ≥ 10 [39].
Similarly, Lagnika et al [36] evaluated toxicity activities of methanol extracts of aerial parts of A. lobata using Artemia salina (brine shrimp) toxicity assay.The brine shrimp lethality test results revealed lethal concentration 50% (LC 50 ) value of 8.17 mg/ml [36].Therefore, the extract tested in his study exhibited very low or no toxicity.Lagnika et al [12] evaluated the toxicological effects of A. lobata aqueous extracts using oral acute toxicity in the rat model with distilled water as control.Acute toxicity of aqueous extracts of tested plants was assessed at a dose of 2000 mg/kg and the rats were observed for signs of toxicity or death after administration of the extracts.Therefore, the lethal dose 50 (DL 50 ) of aqueous extracts of A. lobata was higher than 2000 mg/kg body weight.The results revealed that all tested animals were physically active during the test and no signs of toxicity or morbidity in rats treated with extracts were observed.
A significant decrease of serum alanine aminotransferase and creatinine levels were observed in rats treated with aqueous extract of A. lobata while a significantly increased levels of red blood cells and hematocrit were observed.Histopathological examination of liver and kidney sections of rats treated with 2000 mg/kg body weight of aqueous extracts of A. lobata did not show any changes when compare to control rats.These results indicate that the oral administration of aqueous extracts of A. lobata did not produce any significant toxic effect in rats [12].Therefore, the extract could be considered non-toxic to females rats.These results obtained by Lagnika et al [12,36] indicating the possibility that A. lobata extracts may not be toxic calls for thorough toxicological evaluations as the entire plant is regarded as a hunting poison in the coastal interior of the Ivory Coast [5].The above ground parts of A. lobata are traditionally used in preparing arrow poisons in Ivory Coast [5].

CONCLUSION
A. lobata, which is exotic to tropical Africa, is widely used to combat various human ailments and diseases in the region.Utilization of A. lobata in tropical Africa support the general hypothesis that exotic plants are now recognized throughout the world as an important component of indigenous pharmacopoeia filling therapeutic vacancies that native plants cannot satisfy.Therefore, the use of exotic plant species as herbal medicines can alleviate pressure on scarce and threatened indigenous plant species.The historical traditional usage of A. lobata as herbal medicine in West Africa calls for detailed phytochemical and pharmacological studies aimed at correlating its documented ethnomedicinal uses with the phytochemical and pharmacological properties of the species.There is need for clinical and toxicological evaluations involving the species.There is also need to validate the traditional medicinal applications of A. lobata through tests in vitro and in vivo experiments.Detailed phytochemical and pharmacological studies of the species will provide some insight into the therapeutic potential of A. lobata.The phytochemistry and pharmacological activities of A. lobata and its compounds, as well as mechanisms of action should be studied further, as this is necessary for global acceptance of this plant in traditional and modern medicinal applications.

Table 2 :
Nutrient composition of Astraea lobata leaves, roots and stems per 100 g

Table 3 :
Phytochemical compounds isolated and characterized from Astraea lobata