Ethnobotany, ethnopharmacology and toxicity of Jatropha curcas L. (Euphorbiaceae): A review

Jatropha curcas L. (Euphorbiaceae) is a multiple purpose plant with potential for biodiesel production and medicinal uses. It has been used for treatment of a wide spectrum of ailments related to skin, cancer, digestive, respiratory and infectious diseases. This review aims to provide an up-to-date survey of information available on botany, traditional uses, phytochemistry, pharmacology and toxicity of J. curcas . Establishing a scienti ﬁ c basis that explains its ethnopharmacological uses in order to facilitate and guide future research. The review covers literature available from 1960 to 2012 collected from scienti ﬁ c journals, books and electronic searches such as Google scholar, Web of Science and ScienceDirect. Ethnomedicinal uses of J. curcas have been reported frommanycountriesinAfrica,Asia,SouthAmericaandtheMiddleEastforalmost100differenttypesofailments. The phytochemical studies have shown the presence of many secondary metabolites including diterpeniods, sesquiterpenoids, alkaloids, ﬂ avonoids, phenols, lignans, coumarins and cyclic peptides. Crude extracts and isolated compounds from J. curcas show a wide range of pharmacological activities, such as anti-in ﬂ ammatory, antioxidant, antimicrobial, antiviral, anticancer, antidiabetic,


Introduction
Jatropha curcas is a multiple purpose plant with potential for biodiesel production and medicinal uses.In recent years, increased interest in its seed oil for biodiesel production has encouraged cultivation of the plant on large scale.There are predictions that millions of hectares will come under J. curcas cultivation (Devappa et al., 2011).This would generate huge quantities of raw materials for biodiesel and other potential uses that could open new routes for sustainable ecofriendly development.
A number of reviews were written on the genus Jatropha covering various aspects for example, medicinal properties, phytochemistry and pharmacology (Sabandar et al., 2012;Sharma and Singh, 2012), diterpenes (Devappa et al., 2011), toxicity (Devappa et al., 2010a), nutritional, biochemical, and pharmaceutical potential of proteins and peptides (Devappa et al., 2010b) and chemical constituents (Zhang et al., 2009).Although there are some reviews published recently on medicinal benefits and applications from J. curcas species (Prasad et al., 2012;Sharma et al., 2012;Luis et al., 2012;Kamal et al., 2011;Thomas et al., 2008), there is still a crucial need for an inclusive review that covers the therapeutic and toxicological potential of this species.The present review attempts to collate the available information on the botany, traditional uses, phytochemistry, pharmacology and toxicity of J. curcas.We hope that this review may provide scientific basis that explain the ethnopharmacological use of J. curcas in order to facilitate and guide future research.In particular, we aimed to answer the following questions.(1) What information is available on the traditional uses, botany, phytochemistry and toxicity of J. curcas?(2) What pharmacological studies were performed on this plant and how do they validate its traditional uses? and (3) What is the future for J. curcas?.

Taxonomy and botanical description
The genus Jatropha belongs to the tribe Jatropheae in the Euphorbiaceae family and contains approximately 170 known species (Carels, 2009;Dehgan and Webster, 1979).The botanical name of the genus Jatropha was derived from the Greek word "Jatros" meaning a doctor and "trophe" meaning food (Kumar and Sharma, 2008) which incorporates the historical medicinal uses of this plant.J. curcas L. (Fig. 1) is a dense shrub or small tree 3-5 m in height.It can reach up to 10 m under favourable conditions.It is a diploid species with 2n = 22 chromosomes (Carels, 2009).There are two genotypes found in Mexico classified as toxic and non-toxic (Becker and Makkar, 2008).The life span of the plant is up to 50 years (Achten et al., 2010).It is a deciduous plant with an articulated growth habit with morphological discontinuity (Becker and Makkar, 2008).The root system constitutes a main taproot and four shallow lateral roots (Carels, 2009;Heller, 1996;Neuwinger, 1996).The branches are glabrous with smooth greenish-bronze-coloured bark and translucent latex (Neuwinger, 1996).The leaves are smooth simple, 5-lobed and heart-shaped, 10-15 cm long, dark green, cordate or round, acute at the apex, cordate at the base, alternate and may fall once a year (Dehgan and Webster, 1979;Neuwinger, 1996).The flowers are in axillary clusters with a stalk of 3-5 cm long, bracts entire, lanceolate or linear, densely pubescent, yellowish-green, with prominent glandular discs in the flowers.Male flowers with 5 ovate-elliptic sepals, less than 4 mm long and 5-oblong-obovate petals united in the lower half, densely hairy inside, 6-7 mm long, 8 stamens.Female flowers with free oblong petals and larger sepals, 4 mm long (Abdelgadir et al., 2009;Bhattacharya et al., 2005;Chang-Wei et al., 2007;Raju and Ezradanam, 2002).Fruits are ovoid capsules 3-4 cm long, slightly trilobite, splitting into three cells.The seeds are three per fruit, large, oblong, 2 cm long and sweet tasting (Kochhar et al., 2008;Neuwinger, 1996).

Habitat, distribution and ecology
The center of origin of J. curcas is in the Northeastern part of South America and the dry areas of Mexico (Jongschaap et al., 2007;Makkar et al., 2009).It was reported that the plant was distributed by Portuguese ships via the Cape Verde Islands and Guinea Bissau to other countries in Africa and Asia (Heller, 1996).Currently it is cultivated abundantly in many tropical and sub-tropical regions in Africa and Asia (Schmook and Serralta-Peraza, 1997) as an ornamental tree (Iwu, 1993) or as sturdy hedges (Neuwinger, 1996).J. curcas grows under conditions where the temperature ranges between 15 and 40 °C (Kumar and Sharma, 2008).The plant is not sensitive to day length and may flower any time of the year (Heller, 1996).It grows well under a wide range of rainfall from 250 to over 1200 mm per annum.During low rainfall and prolonged dry periods the plant sheds its leaves as a counter to drought.The plant grows well in well drained soils with good aeration and is well adapted to marginal soils with low nutrient content (Openshaw, 2000).
The unsaturated fatty acids dominate the saturated fatty acids in a ratio of 3:1 (Joshi et al., 2011).The main fatty acids found in J. curcas oil are oleic (41.5-48.8%),linoleic (34.6-44.4%),palmitic (10.5-13%), stearic (2.3-2.8%) in addition to cis-11-eicosenoic and cis-11,14eicosadienoic acids (Martínez-Herrera et al., 2006).Having a high oil and protein content makes the plant a good candidate for many usages and industries.The history of the commercialization of J. curcas was started by the exportation of its seed oil hundreds of years ago from Cape Verde to Portugal for soap production and lamps (Gübitz et al., 1999).The seed oil properties have been sufficiently persuasive to consider it as a substitute for fossil fuels to help reduce greenhouse gas emissions (Abdelgadir et al., 2010).The oil can be used in manufacturing of candles, soaps and cosmetics.The seed cake or kernel meal provides a highly nutritious and economic protein supplement for animal feed if detoxified (Makkar et al., 1998).Recently, Visser et al. (2011) reported the possibility of producing cellulosic methanol from the by-products of J. curcas oil extraction.The plant can be used to prevent soil erosion, reclaim land and as a living fence (Heller, 1996).

Hunting poison
The stem bark or the latex is a fishing poison in some parts of Africa and the Philippines.In Nigeria a mixture of J. curcas seeds and the latex of Euphorbia poisnii or E. unispina mixed with corn is used as bait for hunting guinea-fowl.Some tribes make arrow poison from seed or seed oil of J. curcas and Strophanthus spp. in Nigeria and Burkina Faso.Seeds grated with palm oil are used to kill rats in Gabon (Neuwinger, 1996).These traditional uses as hunting poison are related to the high toxicity of the seed and latex of J. curcas.Table 7 contains a summary of its toxic components and their modes of action.

Uses in traditional veterinary practices and medicine
Most parts of J. curcas have been widely used for veterinary purposes.The seeds are highly effective against Strongyloides papillosus infection in goats (Adam and Magzoub, 1975).Uses of various parts of J. curcas in folk and traditional medicine worldwide have been summarized in Table 1.However, the majority of these observations have not been tested following scientific principles, and therefore, the use of J. curcas plant parts for such applications should be used with caution.All parts of J. curcas have been widely used in west and central Africa (Neuwinger, 1996).The dried plant sap rubbed to a powder  between the hands and applied to wounds is regarded as "penicillin" in The Congo.In Senegal, Nigeria, Congo and East Africa, the leaf, stem sap or the dried powdered plant is spread on flesh wounds as a haemostatic.
In Ivory Coast grilled leaves are crushed together with saliva and the paste is applied to abscesses and wounds.A few drops of diluted water solution of twig sap are given by mouth to new-born babies affected by tetanus.The leaf has been used as haemostatic agent when applied to cuts and bleeding wounds (Neuwinger, 1996).The seeds have been used for treating ascites, gout, paralysis, skin diseases and as a purgative, anthelminthic and abortifacient.In some parts of Africa seeds are chewed when in need of a laxative (Wole and Ayanbode, 2009).The seed oil has been used as ingredient in the treatment of rheumatism (Heller, 1996;Iwu, 1993).

Phenolics
Phenolic compounds are present in all plants and are considered to be biologically active constituents.These compounds have antithrombotic and anti-inflammatory actions because they inhibit or antagonize the platelet activating factor (PAF) which is a potent inflammatory phospholipid mediator (Fragopoulou et al., 2007).A number of phenolic compounds were isolated from different parts of J. curcas (Table 2) such as 3-hydroxy-4-methoxybenzaldehyde and 3-methoxy-4-hydroxybenzoate acid from the root (Ling-yi et al., 1996), caffeoylaldehyde and syringaldehyde from the seed cake (Yao et al., 2012).

Proteins
J. curcas proteins and peptides have been studied for their roles in plant metabolic activities, defense against predators and biological activities.Functional proteins such as aquaporins were isolated from different parts of J. curcas.These proteins play essential roles in plant adaptation to drought stress by controlling the transmembrane water movement.In J. curcas aquaporins play an important role in the rapid growth by the plant during dry weather conditions (Devappa et al., 2010b).Other functional proteins isolated from the plant are: curcin, a lectin Stripe et al. (1976); two esterases (JEA and JEB) and a lipase (JL) (Staubmann et al., 1999b); curcain, a protease from the latex of J. curcas (Nath and Duta, 1997); phytate and a trypsine inhibitor (Makkar and Becker, 1997).Van den Berg et al. (1995) isolated the cyclic peptide curcacyclin A and Auvin et al. (1997) isolated curcacyclin B (Table 2).

Anti-inflammatory effects
The anti-inflammatory activities of different extracts from J. curcas are outlined in Table 3. Anti-inflammatory activity for fractions from ethyl acetate extracts of J. curcas leaves was reported earlier by Staubmann et al. (1999c).Topical application of J. curcas root powder paste on TPA-induced ear inflammation in albino mice (Mujumdar and Misar, 2004).The methanolic extract of J. curcas leaves showed anti-inflammatory effects on Wister albino rats (Uche and Aprioku, 2008).Water extracts from J. curcas bark and leaves showed significant anti-inflammatory activity using the formalin-induced paw edema method in rats (Sanjeetha et al., 2009).The alcoholic extract of roots, stems and leaves of J. curcas exhibited systemic and significant antiinflammatory activity in acute carrageenan-induced rat paw edema (Nayak and Patel, 2010a).The anti-inflammatory effects of J. curcas extracts of leaf, stem bark, root and latex is attributed to their strong iNOS inhibition (Oskoueian et al. (2011b).

Antioxidant activity
The antioxidant activities of different extracts from J. curcas are listed in Table 4.The aqueous, ethanol and methanol extracts besides methanolic extract fractions from nodes, leaves, stems and roots of J. curcas exhibited antioxidant activity (El Diwani et al., 2009;Igbinosa et al., 2011;Oskoueian et al., 2011b).

Antimicrobial activity
The antimicrobial activity of various extracts from different parts of J. curcas is outlined in Table 5, including the information on the methods used, inhibition zone, minimal inhibitory concentration, minimal bacterial concentration and the standards used.Some of the studies included different parts of the plant such as Namuli et al. (2011) who reported antimicrobial activity of the crude aqueous, methanolic and hexane extracts of various plant parts of J. curcas.Antimicrobial activity of alcoholic extracts from J. curcas leaves was reported by Akinpelu et al. (2009) and Irene and Cariňo (2011) for methanol extracts, whereas Sharma et al. (2010b) used ethanol extracts.Antimicrobial activity of J. curcas stem bark was reported in a number of papers.Igbinosa et al. (2009) reported antimicrobial activity of crude ethanolic, methanolic and water extracts of the stem bark of J. curcas.Gupta et al. (2010) found antimicrobial activity for crude petroleum ether, ethyl acetate and methanol extracts beside two other purified compounds JC-1 and JC-2 isolated from the stem bark of J. curcas.Recently, Obasi et al. (2011) reported antimicrobial activity of the methanolic extract in addition to methanolic extract fractions (Chloroform, ethyl acetate and methanol) from stem bark of J. curcas.J. curcas root extracts showed antimicrobial activities against a wide range of microorganism specially those responsible for sexually transmitted diseases.Hexane, ethyl acetate and methanol extracts of J. curcas roots displayed strong antimicrobial activity.However, the methanol extract of the root bark showed potent broad spectrum activity (Aiyelaagbe et al., 2007).The antimicrobial activity of J. curcas latex from stems and leaves was reported by Oyi et al. (2007).The seeds and seed cake of the plant exhibited antimicrobial activities as reported in several papers.Sriprang et al. (2010) reported antibacterial activity for hexane, dichloromethane, acetone and methanol extracts from J. curcas seed cake against Gram-negative and Grampositive bacteria.Donlaporn and Suntornsuk (2010) showed that ethanol extract from J. curcas seed cake exhibited antifungal activity.Later, Daniyan et al. (2011) found antimicrobial activity for methanol, ethyl acetate and hexane extracts from J. curcas seed.Numerous studies and IFN-(recombinant mouse interferon-gamma).2) At 200 μg ml −1 the methanolic extract inhibited the NO as leaf (80.8%) and stem bark (80.6%).3) Latex extract at concentrations between 3.1 and 200 μg ml −1 were not toxic to the raw 264.7 cell.4) At 200 μg/ml, the value of NO inhibition was 93.9% indicating the strong ability of latex extract to inhibit the iNOS while maintaining cell viability comparable to L-NAME.5) Root methanolic extract at concentrations between (3.1-200 μg ml − 1 ) inhibited NO production (93.6-95.8%)similar to L-NAME while, concentrations between 6.2 and 200 μg ml − 1 ) were toxic to the raw 264.7 cell.(2012a) evaluated the antibacterial activity of the phorbol ester-rich fraction isolated from J. curcas oil (Table 5).However, a number of constraints were highlighted by Devappa et al. (2011) mainly that some phytochemicals from the genus Jatropha were not characterized and checked appropriately for bioactivity.Less sensitive, non-specific, or broad spectrum assays have been used for the antimicrobial activities.Besides, most of the studies did not clearly mention the conditions under which the tests were undertaken such as location, climate, harvest and healthy or diseased states.In some studies the phytochemicals were evaluated to determine their bioactivity using microbial susceptibility assays at impractical and inapplicable doses or they lack comparison with the standard active compounds.Further, in some studies the information about selection criteria of microbes used in the experiments were not mentioned.

Anticancer activity
A survey on plant species from the Mexican flora revealed that J. curcas is one of the species that is used for cancer treatments in Mexico (Alonso-Castro et al., 2011).Diterpenes are the major secondary metabolites synthesized by J. curcas.These compounds are proven to be cytotoxic and tumor-inhibitors (Devappa et al., 2011).The anticancer activities of different extracts from J. curcas are presented in Table 6.The methanolic extract fraction from J. curcas leaves showed antimetastatic activity (Balaji et al., 2009a).Extracts from leaf, root and stem bark of J. curcas showed cytotoxic activity on an HT-29 cell line.The root extract was more active compared to leaf and stem bark suggesting its candidacy as a source of an anticancer therapeutic agent (Oskoueian et al., 2011b).Anticancer activities by diterpenes isolated from J. curcas plant have been reported in several papers.Goel et al. (2007) stated that phorbol esters are co-carcinogens which themselves do not induce but promote tumours.Antimetastatic activity of curcusone B against 4 human cancer cell lines was reported by Mungman et al. (2005), whereas Devappa et al. (2011) reported antimetastatic activity against a cholangiocarcinoma cell line (KKU-100 cells).Pertino et al. ( 2007) reported gastro-protective activity from jatropholone (A and B) in an HCl/EtOH-induced gastric lesion model in mice.Sutthivaiyakit et al. (2009) reported cytotoxicity for caniojane against African green monkey kidney fibroblasts and antituberculosis effects against Mycobacterium tuberculosis H37Ra.Theoduloz et al. (2009) reported anti-proliferative activity of jatropholone B against fibroblasts CCL-171, AGS CRL-1739, lung HTB-58, bladder HTB-1 and leukemia CCL-240.In contrast, Wang et al., 2009 reported no significant inhibitory activity in vitro for jatrophalactam against a human lung cancer cell line A549, colon cancer HT-29, and epidermal squamous cell carcinoma A431.Recently, Liu et al. (2012) reported cytotoxic activity for jatrophalactone.Anticancer activities of proteins isolated from J. curcas have been studied for a number of decades.Stripe et al. (1976) isolated the Ribosome-Inactivating Proteins (RIPs) curcins from J. curcas seeds.These proteins are considered as cellkilling agents that can inhibit cell-free protein synthesis.Luo et al. (2007) reported antitumor activity of curcin in Escherichia coli strain M15.The protein synthesis was inhibited in the cell-free translation system.Regarding the cytotoxicity studies on the genus Jatropha Devappa et al. ( 2011) stated that phytochemicals studied for cytotoxicity and antitumor activities using cell lines lack the proper reference compounds.Cell-based activities are less sensitive, more variable and the cytotoxicity of the interested compounds may mask a more specific activity.et al. (1995) reported a moderate cycloprotective activity against HIV in cultured human lymphoblastoid CEM-SS cells for the methanol extract from J. curcas.Matsuse et al. (1999) investigated the effects of aqueous and methanolic extracts from J. curcas branches for the inhibition of HIV-induced cytopathic effects in cultured cells, HIVreverse transcriptase and HIV-protease enzymes.The water extract of J. curcas branches showed potent inhibition (IC 50 24 μg ml −1 ) of the HIV-induced cytopathic effects with low cytotoxicity (CC 50 N 1000) and selectivity index CC 50 /IC 50 (N 41.7).Recently, Wender et al. (2008) reported the possibility of synthesizing prostratin and DPP from phorbol esters from J. curcas.This synthesis facilitates the identification of superior clinical candidates that could be used in the treatment of HIV.

Antidiabetic activity
Traditionally leaf infusion (Jaiswal, 2010), decoctions of boiled leaves or fruit burnt into ashes (Gbolade, 2009), water extract of the bark (Jayakumar et al., 2010) are used to control blood sugar levels.However, the scientific information available regarding human models is very scarce and research is needed to cover this aspect in the near future.Mishra et al. (2010) reported antihyperglycemic effects of 50% ethanolic extract from J. curcas leaves by oral administration in allaxon-induced diabetic rats.The extract at doses of 250 and 500 mg ml − 1 bw respectively, showed potent antihyperglycemic activity LD 50 2500 mg kg − 1 .Reduction in glucose level in treated rats was 219.5-116.5 and 237-98.8for the doses of 250 and 500 mg kg −1 , respectively.The results were comparable to reduction in rats treated with the standard glibenclamide 232-94.5 at 600 μg kg −1 .

Oskoueian et al. (2011b)
The root and stem bark showed moderate and weak activities (IC 50 57.9and N200 μg ml −1 ), respectively.All samples exhibited NO scavenging activity in a dose-dependent manner Stem bark Methanol, ethanol and water Antioxidant activity using DPPH, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), ferric reducing, nitric oxide (NO), superoxide anion, (O 2 −) and hydrogen peroxide (H 2 O 2 ) assays.Butylated hydroxyl toluene (BHT) and ascorbic acid were used as standards.The higher the concentration the higher DPPH scavenging activity.The methanolic extract showed the highest DPPH scavenging activity followed by aqueous and ethanolic extract but possess high DPPH scavenging activity compared with the standard BHT.The inhibition of ABTS radical by the extracts was also concentration dependant.

Igbinosa et al. (2011)
The scavenging activity of ABTS + for the three extracts was high.All extracts exhibited higher superoxide radical scavenging activity when compared with BHT In addition, the extract significantly reduced the cholesterol and triglyceride levels in the rats.

Analgesic activity
Uche and Aprioku (2008) reported analgesic activity of methanolic extract from J. curcas leaves in mice using the acetic acid-induced writhing test.The methanolic extract caused significant reduction in the number of acetic acid-induced writhing in mice compared to the analgesic effect obtained from the reference drug paracetamol.In another study Yusuf and Maxwell (2010) studied the analgesic activity in vivo of the methanolic leaf extract from J. curcas using hot plate and acetic acid-induced writhing reflex in mice and tail flick or immersion method in rats.In the hot plate and tail flick models, oral administration of the leaf extract at doses of 100, 200 and 400 mg kg −1 and the reference drug acetylsalicylic 400 mg kg −1 showed a potent analgesic effect by increasing the pain time dose dependant in mice and rats.In the acetic acid-induced writhing reflex model, the extract decreased the number of abdominal contortions.Nayak and Patel (2010b) reported that alcoholic extract from stem and roots of J. curcas showed significant activity and produced significant reduction in yeast-induced pyrexia compared to the standard drugs pantazocine and paracetamol, respectively.Balaji et al. (2009b) evaluated the methanolic fractions from J. curcas leaves against hepatocellular carcinoma induced by aflatoxin B 1 by oral administration in rats at doses of 100 and 200 mg kg −1 .The methanolic fractions decreased the levels of elevated serum enzymes, lipid levels and bilirubin and increased the protein and uric acid levels.The liver histopathology showed that the methanolic fractions reduced incidence of liver lesions, lymphocytic infiltrations and hepatic necrosis induced by aflatoxins.

Wound healing activity
The traditional use of different parts of J. curcas for wound healing is documented in many parts of the world (Neuwinger, 1996;Osoniyi and  Ethanol, methanol and water Activity against E. coli, S. aureus, Klebsiella pneumonia, Proteus mirabills, P. aeruginosa, C. albican, S. epidermis, Shigella dysenteriae, Micrococcus Kristinae, B. cereus, Bacillus subtillis, Proteous vulgaris, and Serratia marcescens with zones of inhibition ranges as 5-12, 8-20 and 0-8 mm for ethanol, methanol and water extract, respectively.MBC ranged between 2.0 and 12.5 mg ml −1 for ethanol and 2.0-20.0mg ml −1 for the methanol extract   (1997) reported positive cicatrizant activity by J. curcas extract in mice.Shetty et al. (2006) evaluated the wound healing activity of crude bark extract from J. curcas in Wistar albino rats.The extract accelerated the healing processes by increasing the skin breaking strength, granulation tissue breaking strength, wound contraction, dry granulation tissue weight and hydroxyproline levels.Esimone et al. (2009) tested the wound healing activity of herbal ointment containing methanolic extract from J. curcas leaves incorporated into 10 g of simple ointment base.Ointment was applied topically to the wound at intervals of 3 days until complete wound closure.Blank ointment and gentamicin ointment (1%) served as standard and control respectively.The methanol extract incorporated into an ointment base caused higher rates of wound healing and reduced the epithelialisation period in a dose-related manner.

Anticoagulant and procoagulant activity
Traditionally the leaf, stem sap or the dried powdered plant of J. curcas is spread on flesh wounds as haemostatic (Neuwinger, 1996;Watt and Breyer-Brandwijk, 1962).Osoniyi and Onajobi (2003) reported that J. curcas possess both procoagulant and anticoagulant activities as the latex from J. curcas significantly reduced the clotting time of human blood.However, diluted latex, prolonged the clotting time.They attributed the occurrence of these two opposing activities to the solvent partitioning of the latex with acetyl acetate and butanol.At low concentration, the acetyl acetate fraction showed procoagulant activity, while the butanol fraction had the highest anticoagulant activity.
4.11.Antifertility activity (abortifacient activity) Goonasekera et al. (1995) reported antifertility activity by oral administration of methanol, petroleum ether and dichloromethane extracts from J. curcas fruits to pregnant rats.The fruit extracts caused foetal resorption by interrupting pregnancy occurrence at an early stage after implantation.Makonnen et al. (1997) reported antiimplantation and antifertility effects of crude seed extract of J. curcas when administrated orally to female albino pigs.Odusote et al. (2002) reported inhibition of pup birth by J. curcas oil at a dose of 2 ml kg −1 BW.

Toxic and antinutritional components
The major toxic and antinutritional components from J. curcas and their molecular mechanisms are summarized in Table 7. Phorbol esters and curcin are the most toxic phytochemicals of J. curcas (Devappa et al., 2010a).The seeds contain major toxic components as the phorbol esters, the antinutritional phytate and the trypsin inhibitor factors.In the study by Devappa et al. (2012b) J. curcas kernels were separated into cotyledons, hypocotyls, kernel coat and endosperm to determine the location of the antinutrients.Their results showed that majority of phytate (96.5%), trypsin inhibitor (95.3%) and phorbol esters (85.7%) were localised in the endosperm.

Toxicological effects in the in vitro and in vivo models
J. curcas exhibited toxicity to a wide variety of species i.e. microorganisms, animals including humans.All parts of J. curcas are toxic and Gastro-protective activity in HCl/EtOH-induced gastric lesions model in mice.Jatropholone A reduced the lesion by 54% in a doserelated manner at the highest dose of 100 mg kg −1 while, jatropholone B reduced the lesions by 83-91% at all the doses.The cytotoxicity of jatropholones was evaluated against fibroblasts and AGS cells.Jatropholone B was non-cytotoxic to both AGS cells and fibroblasts (N1000 μM), while jatropholone A showed a selective effect against AGS cells (IC 50 , 49 μM) and non-toxic towards fibroblasts (N1000 μM).The test reference compound, lansoprazole exhibited a gastro -protective effect of 73% at 9.4 mg kg −1 , cytotoxic to AGS cells and fibroblasts at 162 and 306 (IC50, μM)

Theoduloz et al. (2009)
Anti-proliferative effects (IC 50 in μM) at a concentration of N100 (μM) against the above cell lines Jatrophalactam No significant inhibitory activity in vitro against human lung cancer cell lines A549, colon cancer HT-29, and epidermal squamous cell carcinoma A431 Wang et al., 2009 the degree of toxicity varies with the extract types, nature of test substances, dose, mode of administration, and sensitivity of the animals (Devappa et al., 2010a).The seeds are toxic to humans (Heller, 1996;Gandhi et al., 1995) with symptoms of giddiness, vomiting, delirium, muscle shock, decrease of visual capacity, high pulse rate and diarrhoea (Becker and Makkar, 1998;Rai and Lakhanpal, 2008;Singh et al., 2010).

Conclusions
J. curcas is a multiple purpose plant with potential for biodiesel production and medicinal uses.The plant has a long history of usage in treatments of a wide range of ailments in many countries.The present review attempted to provide information available on botany, traditional uses, phytochemistry, pharmacology and toxicity of J. curcas covering literature available from 1960 to 2012.The review has shown diverse traditional uses of J. curcas that differ from one country to another.However, the treatments of gastric problems, inflammatory disorders, sexual diseases, jaundice, diabetes, dysentery, fever, and skin diseases are most common.Reports on the use of J. curcas for the same ailments in different continents clearly indicate its strong potential for biological activities.The pharmacological studies on the extracts and metabolites from this plant have mostly been performed in vitro and in vivo with animals.These studies have demonstrated various pharmacological activities such as antiviral, anti-inflammatory, antimicrobial, anticancer, antidiabetic, hepatoprotective and anticoagulant.In relation to the constituents contributing to medicinal values, the findings indicated that diterpenes are mainly responsible for antiinflammatory, cytotoxicity and antimicrobial activities.Phenolics, flavonoids and saponins are responsible for antimicrobial and antioxidant activities.Sesquiterpenoids are responsible for antimicrobial and analgesic effects, proteins such as curcain are responsible for wound healing.Lignans and steroids are responsible for the cytotoxicity and antidiabetic activities, respectively.The detailed pharmacological studies presented in this review provides pragmatic documentation for J. curcas traditional uses, and reveals that this plant may be considered as potential source for medicinal molecules.However, there are challenges for the reproducibility of biological activities in relevance to the practical significance.Thus, analytical and standardization protocols of plant materials should be developed for J. curcas, since these are the bases for reproducible pharmacological studies.Further research is needed to study the physiological and biochemical functions demonstrated by J. curcas, identify the individual bioactive natural products, and illustrate their mechanism of action.Caution is to be taken when using the different parts of J. curcas in traditional medicine.The antagonistic properties of the phytochemical such as antitumor and tumor promotion properties in J. curcas plant extracts suggest caution in the traditional uses and applications.Further studies are required to determine the mechanism and conditions that control these controverting properties.The therapeutic utilization may be ideal when the active compounds are used in purified form.Prevent the absorption of minerals (Zn, Fe, Ca and Mn in the gastrointestinal tract and affecting protein digestibility by the formation of the complex protein-phytic acid Devappa et al. (2010a)

Table 1
Uses of different plant parts of Jatropha curcas in folk and traditional medicine.
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Table 3
Anti-inflammatory activity from different extracts of different parts of the Jatropha curcas plant.
1).Inhibition of NO production from macrophages RAW 264.7 cells, induced by LPS (Escherichia coli lipopolysaccharide)

Table 4
Antioxidant activity of different extracts from different parts of the Jatropha curcas plant.-diphenyl-2-picrylhydrazyl hydrate) assay.The crude extract from roots has the higher free radical scavenging activity with maximum inhibition of 0.521 mg ml −1 DPPH and nitric oxide (NO) scavenging activity assays.The IC 50 values for DPPH scavenging activity for latex, leaf extracts, quercetin and vitamin C were 6.8, 5.9, 4.2 and 10.6 μg ml −1 , respectively.Good NO scavenging activity was shown by latex IC 50 29.7 and leaf IC 50 93.5 μg m l −1 .

Table 5
Antimicrobial activities of extracts from different parts of the Jatropha curcas plant.Escherichia coli, Staphyllococcus aureus and Pseudomonas aeruginosa Akinpelu et al. (2009) Ethanol Activity against E. coli, P. aeruginosa, P. fluorescens and S. aureus.MIC values ranged between 6 and 11 mm.

Table 6
Anticancer activities of extracts from different parts of the Jatropha curcas plant.Antimetastatic activity using B 16 F 10 melanoma cells in C57BL/6 mice.Administration of the methanolic fraction at the dose of 100 and 200 mg kg −1 inhibited the metastatic colony formation of the melanoma in lungs by 47.5 and 69.5% respectively.The methanolic fraction was in vitro cytotoxic against B 16 F 10 melanoma IC 50 24.8μgml −1 and reduced the levels of lung collagen hydroxyproline, hexoxamine, uronic acid contents, levels of serum aialic acid in the treated animals Cytotoxic activity by leaf extract IC 50 199.1 μg ml −1 , stem bark IC 50 N 200 μg ml −1 in HT-29 cell line.The root extract at 25 μg m l −1 decreased the HT-29 cell viability to 28.8%.Increase in extracts concentration up to 200 μg ml −1 reduced the cell viability significantly in a dose-dependent manner.Eschericia coli strain M15.At concentration of 50 μg ml −1 the curcin inhibited the growth of tumor cells of cellule pulmonary cancer and gastric cancer in a a concentration-dependant mode African green monkey kidney fibroblasts IC 50 12.9 μg ml −1 and test reference ellipticine as IC 50 0.7 μg ml−1

Table 7
Toxic and antinutritional components of J. curcas., platelet aggregation and metabolic activity.Promotes tumor as they mimic the action of diacyl glycerol stimulator of the protein kinase C (PKC) Binding and inactivate the pancreatic proteolytic enzymes (trypsin and chymotrypsin).Interfere with the physiological process of proteins digestion, causing disorders of the pancreas, reduction in the digestibility of proteins in the diet and growth decrease Agglutination of erythrocytes in animals, binding specific carbohydrates, mainly in cells of the duodenum and jejunum, causing serious damage to the intestinal wall -affect the turnover and loss of gut epithelial cellsinterfere with nutrient digestion and absorptiondamaging the luminal membranes of the epitheliummodulate the immunological status of the digestive tract.SeedInhibit prokaryotic and eukaryotic ribosome by specific modification of the larger rRNA.Protein translation inhibitory activity or N-glycosidase activity like other type Devappa et al. (2010a) Stripe et al. (1976) Lin et al. (2002).Has ability to form foam in aqueous solutions, causing haemolytic disorder and complex changing in steroids.Causes changes in the permeability of the intestinal mucosa, inhibiting nutrients transport