MEDICAL BENEFIT, PHARMACOLOGY AND TOXICITY OF JATROPHA CURCAS L. (EUPHORBIACEAE) : A REVIEW

Bossou Annick Flore Arlette Dohoué, Olayé Théophile, Bogninou Gbêdossou Sophie Reine, Koudoro Yaya Alain, Agbangnan Dossa Cokou Pascal, Bothon F. T. Diane, Alitonou Guy Alain, Avlessi Félicien and Sohounhloue C. K. Dominique Laboratoire d’Etude et de Recherche en Chimie Appliquée (LERCA), Ecole Polytechnique d'Abomey Calavi (EPAC), Université d'Abomey-Calavi (UAC), 01 BP 2009 Cotonou République du Bénin. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 30 November 2019 Final Accepted: 31 December 2019 Published: January 2020

Plants have long been used in traditional medicine to cure diseases and for that reason, they have also been a source of bioctives compounds for the development of pharmaceutical compounds. Jatropha curcas is one these plants known for its multiple purpose use. The present study was carried to check out through the litterure, the tradional use of this plant, the bioctive compounds isolated from it and some pharmacological properties evaluated by scientists. As a result, we found out that the traditional use of this plant is well known. Many bioactive compounds have been isolated from different parts of Jatropha curcas most of which are diterpene, sesquiterpene and triterpene. Those bioactive compounds could justify the traditional use of this plant. Many antimicrobial and antioxydant activities have been done but few studies were dedicated to its toxicity. So there is need to carry out more toxicity study in other to guarenty the safe use of this plant.

…………………………………………………………………………………………………….... Introduction:-
In all the developing countries, especially in the Continent of Africa, the majority of the common people continue to rely heavily on the use of medicinal plants as their primary source of healthcare. The International Development Research Centre (IDRC) gave one estimate which puts the number of Africans who routinely use the traditional medicinal services for primary health care as high as 85% in Sub-Saharan Africa. Even recent reports suggest that 60%-80% of the people in Africa rely on traditional remedies to treat themselves for various diseases (van Wyk, 2008) Now, with 70-80% of Africa's population relying on traditional medicines, the importance of the role of medicinal plants in the healthcare system being enormous, also Africa is endowed with many plants that can be used for medicinal purposes in the future. In fact, out of the approximated 6400 plant species in tropical Africa, more than 4000 are used as medicinal plants (WHO, 2007). As most of the modern drugs have been developed from knowledge and materials from medicinal plants use, serious attention has now been given on this sector, as is evidenced by the recommendation of the World Health Organization in 1970 (Wondergem et al., 1989).
Traditional medicinal plants have been recognized as a rich source of candidate compounds for the development of pharmaceuticals (Carvalho et al. 2018). The genus Jatropha belongs to the family Euphorbiaceae and has a great variety of species, among them J. multifida, J. curcas, J. molissima, J. gossypifolia that are currently the source of 857 studies for the production of biodiesel and also for the medicinal character that have. They are used in traditional folklore medicine to cure various ailments in Africa, Asia and Latin America. (Devappa et al, 2010). Their usage as traditional health remedies is the most popular for 80% of the world population in Asia, Latin America and Africa and is reported to have minimal side effects (Cowan, 1999). In this genus, Jatropha curcas have played major role in the treatment of various diseases, including bacterial and fungal infections. All parts of Jatropha (seeds, leaves, bark, etc) have been used in traditional medicine and for veterinary purposes for a long time (Prasad et al., 2012). The purpose of this review is to provide information about J. curcas medicinal uses on each part of this plant and to present the contribution of scientists in the discovery of it potential use in the field of research and pharmacological applications. In this work, we present not only the medical use of J. curcas but also the phytochemical compounds already isolated from this plant along with their pharmacological activities.
Medicinal Benefits:-J. curcas is a multiple purposes plant and various parts of the plant is use in folk and traditional medicine worldwide. Table 1 summarized some of the use of various part of J. curcas. 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 Congo. In Senegal, Nigeria, Congo and East Africa, the leaf, stem sap or the dried powdered plant is spread on fleshwounds 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;Staubmann et al., 1999c). In Southeast Asia and in some regions of Africa, the leaves are used as purgative while in Cape Verde and Cameroon, the decoction of the leave is used internally and externally against fever. In Cameroon, the leaves are also in use as the remedy against rheumatism and in Nigeria against jaundice (Staubmann et al., 1999c). In India, the juice from leaves is used to cure diseases such as dysentery and colic and are also applied to the breast to promote lactation (Parveen et al., 2007).In many part of the world, the seeds are used to ascites, gout, paralysis, skin diseases and as a purgative, anthelminthic, abortifacient and as a laxative (Wole and Ayanbode, 2009). The seed oil has been used as ingredient in the treatment of rheumatism (Heller, 1996;Iwu, 1993). In Benin Republic, the decoction of the leaves together with the roots and the fruits of Xylopia ethiopica is used as drink to treat drepanocytosis while the fresh leaves mixte with kaolin pounded in water is also used as a drink for the treatment of haemorrhoids (Neuwinger, 1996). In Benin Republic, the latex is used as a mouth rinse to treat bleeding gums and to sooth a baby's inflamed tongue. In the Philippines, Indonesia and in Benin Reuplic, a little latex on absorbent cotton is used to cure a toothache. . In the island of Tonga, in Oceania, the leaves of J. curcas have been used in folk medicine to treat vaginal bleeding (Singh et al., 1984). Fagbenro-Beyioku (1998) investigated and reported the anti-parasitic activity of the sap and crushed leaves of J. curcas. In Mali, the leaves are used as treatment for malaria (Henning, 1997). The leaves are utilized extensively in West Africa ethnomedical practice in different forms to cure various ailments like fever, mouth infections, jaundice, guinea worm sores and joint rheumatism (Oliver-Bever, 1986).

Bioactive compounds from J. Curcas :-
The review of the littérature shows that J. curcas is a plant with many bioactive compounds, especially from the familly of diterpene, sesquiterpenoids and triterpenes. In fact among the 76 compounds that were identify by Abdelgadir and Staden (2013)  Parekh and Chanda (2007) reported that tannins reacted with proteins to provide the typical tanning effect which is important for the treatment of inflamed or ulcerated tissues. Herbs that have tannins as their main components are astringent in nature and are used for treating intestinal disorders such as diarrhea and dysentery (Dharmananda, 2003). From these observations, J. curcas is used in herbal cure remedies. The biological activities of tannins had been observed to have anticancer activity and can be used in cancer prevention, thus suggesting that J. curcas has the potential as a source of important bioactive molecules for the treatment and prevention of cancer (Li et al., 2003). 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. At 200 μg ml −1 the methanolic extract of the leaf and stem bark inhibited the NO respectively with the percentage of 80.8% and 80.6%. Mujumdar and Misar (2004) observed the anti-inflammatory activity of topical application of J. curcas root powder paste, on TPAinduced ear inflammation in albino mice. Similarly, Uche and Aprioku (2008) reported the inhibition activity of J. curcas leaf extract, on the egg albumin induced inflammation in Wister albino rats. Among plant parts, latex seemed to be promising as an antiinflammatory agent, as it strongly inhibited iNOS and at the same time was non-toxic to raw 264.7 cell. Jatropha curcas can be recommended for acute inflammatory disorders and diseases associated with pains. This also supports its use traditionally as an anti-snake bite, rheumatism and anti-cancer or anti-tumor agent. curcas using DPPH (1,1-diphenyl-2-picrylhydrazyl hydrate) assay. The results show that the crude extract from roots has the higher free radical scavenging activity with maximum inhibition of 0.521 mg ml −1 . According to Oskoueian et al., (2011), latex and leaf extracts showed similar scavenging activity when compared to quercetin and vitamin C. The IC 50 values for DPPH scavenging activity for latex and leaf extracts, quercetin and vitamin C were 6.8, 5.9, 4.2 and 10.6 g/ml. According to the same authors the results of NO scavenging activity demonstrated that latex and leaf were good scavengers with IC 50 values of 29.7 and 93.5 μg/ml, respectively. The results of NO scavenging activity demonstrated that latex and leaf were good scavengers with IC 50 values of 29.7 and 93.5 μg/ml, respectively. Rofida (2015) evaluated the antioxydant activity of different part of Jatropha curcas by DPPH method and found out that the IC 50 are 79,57 ±7,6 µg/mL for leaves 420,98 ± 77,57 µg/mL for the fruits, 26,44 ± 4,99 µg/mL for stem bark and 58,86 ±1,38 µg/mL for the roots whereas ascorbic Acid used as contrôle for far active than all the diffrents extracts of J. curcas had an IC 50 of 2,25 ± 0,32 µg/mL. Recently Osman et al., 2017 studied the antioxydant activity of different fractions (hexane, chloroform, ethyl acetate, n-butanol and water) of the root of J. curcas using three methods. The IC 50 value of gallic acid in the DPPH assay was 26.8 μg/mL. Ethyl acetate fraction possessed the lowest IC 50 value of 85.4 μg/mL According to the same authors, the ethyl acetate fraction exhibited the highest with a value of 79.6% at the concentration of 100 μg/mL while reducing power of ascorbic acid was 94.7% at the same concentration.

Cytotoxicity:-
The cytotoxicity of experimental moieties (ranging from 200 mg/mL to 6.25 mg/mL) was determined using both Vero cell lines as well as PBMCs by MTT assay. The 50% cytotoxic concentration (CC 50 ) values were then calculated using GraphPad Prism software. The CC 50 values were 32.07 mg/mL and 35.5 mg/mL for Aqueous and Methanolic Extracts respectively . According to Patil et al., (2013), aqueous and methanol extracts of the leaves were found to be non toxic to Madin darby canine kidney cells below concentration of 15.57 and 33.62 mg/mL respectively. Root extract appeared to be more active compared to leaf and stem bark on both cell lines. Interestingly, 25 g/ml of root methanolic extract decreased the HT-29 cell viability to 28.8% while the Chang liver cell viability was 72.4%. The IC 50 concentration for HT-29 and Chang liver cell lines were 18.3 ± 0.98 and 33.3 ± 0.75 g/ml respectively. Thus, root methanolic extract could be a source of anticancer therapeutic agent against HT-29 cell line (Oskoueian et al. 2011).

Conclusion:-
The present study which was dedicated to the litterure review of the ethnopharmacology property of J. curcas shows once again that plants are a rich source of bioactive compounds. Many bioactive compounds have been identify in different parts of this plant. This could justify the fact that J. curcas and its other species are used in traditionnal medicine in most part of the world. The antimicrobial activity of this plant appears cleary in the litterure but there are few studies dedicated to its toxicity. So there in need of more study to be sure of the toxicity of J. curcas for its safe use in traditional medicine.