Development and in vivo evaluation of lipid-based nanocarriers containing Jatropha isabellei dry extract from the dichloromethane fraction intended for oral treatment of arthritic diseases

In this study, a dichloromethane fraction dry extract from the underground parts of Jatropha isabellei (DFJi) was used to prepare lipid nanocarriers (LNCJi) aimed at providing the oral delivery of terpenic compounds in the treatment of arthritis. The lipid nanocarriers were prepared by the spontaneous emulsification method. The lipid nanocarriers displayed sizes ranging from 180 to 200 nm and zeta potential values of around -18 mV. A high value of entrapment efficiency (> 90%) was obtained for jatrophone, which was used as the chemical marker of DFJi. LNCJi stored at 4°C were demonstrated to be stable through measurements of transmitted light after analytical centrifugation of the samples. In vitro drug release studies conducted in biorelevant dissolution media demonstrated that jatrophone release was faster from LNCJi than from free DFJi. When tested in an acute arthritis model, the LNCJi exhibited antinociceptive properties after oral administration of a 50 mg/kg dose, unlike the free DFJi, although no reduction in articular diameter was observed. These results suggest that an increase in the oral absorption of DFJi constituents may have occurred through the carrying of this fraction in LNCJi, thus improving the antinociceptive activity of this compound

Larvicidal, cytotoxic and genotoxic effects of aqueous leaf extract ofJatropha mollissima (Pohl) Baill / Efeitos larvicida, citotóxico e genotóxico do extrato aquoso das folhas de Jatrophamollissima (Pohl) Baill

The present study aimed to evaluate the larvicidal effect of aqueous leaf extract fromJatropha mollissima on the larvae of Aedes aegypti and analyze its cytotoxic and genotoxic activity in the Alliumcepa test. Larvae of the mosquito were exposed to the negative and positive controls (distilled water anddiflubenzuron, 0.003 mg mL-1, respectively) and to leaf extract concentrations of 0.001, 0.005, 0.01, 0.02,0.04, 0.06, 0.08 and 0.1 mg mL-1. The mortality rate was evaluated every 24 hours over five days. For thecytotoxic and genotoxic analyses, roots of A. cepa were exposed to the negative (distilled water) and positivecontrol (trifluralin, 0.84 ppm) and to different leaf extract concentrations (0.01, 0.1, 1 and 10 mg mL-1) for24 hours. The statistical analyses were performed by Kruskal-Wallis test (p < 0.05). The leaf extractpresented promising larvicidal activity at the concentrations of 0.08 and 0.1 mg mL-1, and none of theconcentrations evaluated in A. cepa exhibited cytotoxic or genotoxic effect. Since the larvicidal action of J.mollissima and the absence of cellular toxicity have been demonstrated, further studies are recommended todetermine the mechanism of action of the extract as a possible natural larvicide.

O presente estudo teve como objetivo avaliar o efeito larvicida do extrato aquoso das folhas deJatropha mollissima sobre as larvas de Aedes aegypti e analisar sua atividade citotóxica e genotóxica no testeAllium cepa. As larvas do mosquito foram expostas aos controles negativo e positivo (água destilada ediflubenzuron, 0,003 mg mL-1, respectivamente) e ao extrato foliar nas concentrações de 0,001; 0,005; 0,01;0,02; 0,04; 0,06; 0,08 e 0,1 mg mL-1. A taxa de mortalidade foi avaliada a cada 24horas durante cinco dias.Para as análises citotóxica e genotóxica, as raízes de A. cepa foram expostas ao controle negativo (águadestilada) e positivo (trifluralina, 0,84 ppm) e nas concentrações (0,01; 0,1; 1 e 10 mg mL-1) do extrato foliarpor 24 horas. Análises estatísticas foram realizadas pelo teste de Kruskal-Wallis (p < 0,05). O extrato foliarapresentou atividade larvicida promissora nas concentrações de 0,08 e 0,1 mg mL-1, e nenhuma dasconcentrações avaliadas em A. cepa exibiu efeito citotóxico ou genotóxico. Uma vez demonstrada a açãolarvicida de J. mollissima e a ausência de toxicidade celular, mais estudos são recomendados para determinaro mecanismo de ação do extrato como um possível larvicida natural.

Use of a mixture of vegetal (Jatropha curcas) and animal (fish silage) byproducts as protein source in shrimp (Litopenaeus vannamei) diets

This study evaluated growth responses of white shrimp Litopenaeus vannamei by testing different combinations of Jatropha curcas kernel meal (JCK) and tilapia waste silage (FS) as dietary protein sources under laboratory and pond conditions. A reference diet (RD) based on fish meal was elaborated to contain 35% crude protein and 434 kcal/g; then, five isoproteic and isoenergetic experimental diets were formulated from RD with different FS/JCK proportions as follows: 75%FS/0%JCK; 56.25%FS/13.25%JCK; 26.5%FS/30.89%JCK; 18.75%FS/39.75%JCK; and 0%FS/53%JCK. For the laboratory trial, shrimp (2.90 g) were stocked at 10 m2 in an indoor recirculating system during 90 days. There were differences among the growth parameters of diets. Mean weight gain fluctuated from 6.71±0.61 g observed for the shrimp fed the 75%FS/ 0%JCK diet, to 9.70±0.61 g for the group fed the RD. The RD and 18.75%FS/39.75%JCK diet obtained the highest mean final weight (above 12 g), weight gain (above 9 g), and specific growth rate values (above 1.6%/day). Average final survival was 90.97%. The RD and 18.75%FS/39.75%JCK diets were used for the pond trial. Shrimp (0.49 g) were stocked at 10 m2 within 1-m3 cages into the pond for 35 days. Weight gain (3.47 g) and survival (93.33%) of shrimps were similar between the diets. Quadratic equations with the laboratory data indicated that the maximum responses for growth parameters correspond to FS and JKC inclusion levels in the range of 27.83 to 29.00%, and 32.25 to 33.64%, respectively. A combination of 18.75% FS/39.75%JCK meals as protein source is a potential alternative to effectively substitute FM in practical diets for L. vannamei at the studied ages under both laboratory and pond conditions.(AU)

Larvicidal, cytotoxic and genotoxic effects of aqueous leaf extract ofJatropha mollissima (Pohl) Baill / Efeitos larvicida, citotóxico e genotóxico do extrato aquoso das folhas de Jatrophamollissima (Pohl) Baill

The present study aimed to evaluate the larvicidal effect of aqueous leaf extract fromJatropha mollissima on the larvae of Aedes aegypti and analyze its cytotoxic and genotoxic activity in the Alliumcepa test. Larvae of the mosquito were exposed to the negative and positive controls (distilled water anddiflubenzuron, 0.003 mg mL-1, respectively) and to leaf extract concentrations of 0.001, 0.005, 0.01, 0.02,0.04, 0.06, 0.08 and 0.1 mg mL-1. The mortality rate was evaluated every 24 hours over five days. For thecytotoxic and genotoxic analyses, roots of A. cepa were exposed to the negative (distilled water) and positivecontrol (trifluralin, 0.84 ppm) and to different leaf extract concentrations (0.01, 0.1, 1 and 10 mg mL-1) for24 hours. The statistical analyses were performed by Kruskal-Wallis test (p < 0.05). The leaf extractpresented promising larvicidal activity at the concentrations of 0.08 and 0.1 mg mL-1, and none of theconcentrations evaluated in A. cepa exhibited cytotoxic or genotoxic effect. Since the larvicidal action of J.mollissima and the absence of cellular toxicity have been demonstrated, further studies are recommended todetermine the mechanism of action of the extract as a possible natural larvicide.(AU)

O presente estudo teve como objetivo avaliar o efeito larvicida do extrato aquoso das folhas deJatropha mollissima sobre as larvas de Aedes aegypti e analisar sua atividade citotóxica e genotóxica no testeAllium cepa. As larvas do mosquito foram expostas aos controles negativo e positivo (água destilada ediflubenzuron, 0,003 mg mL-1, respectivamente) e ao extrato foliar nas concentrações de 0,001; 0,005; 0,01;0,02; 0,04; 0,06; 0,08 e 0,1 mg mL-1. A taxa de mortalidade foi avaliada a cada 24horas durante cinco dias.Para as análises citotóxica e genotóxica, as raízes de A. cepa foram expostas ao controle negativo (águadestilada) e positivo (trifluralina, 0,84 ppm) e nas concentrações (0,01; 0,1; 1 e 10 mg mL-1) do extrato foliarpor 24 horas. Análises estatísticas foram realizadas pelo teste de Kruskal-Wallis (p < 0,05). O extrato foliarapresentou atividade larvicida promissora nas concentrações de 0,08 e 0,1 mg mL-1, e nenhuma dasconcentrações avaliadas em A. cepa exibiu efeito citotóxico ou genotóxico. Uma vez demonstrada a açãolarvicida de J. mollissima e a ausência de toxicidade celular, mais estudos são recomendados para determinaro mecanismo de ação do extrato como um possível larvicida natural.(AU)

Histopathological and Reproductive Evaluation in Male Rats Fed Jatropha curcas Seed Cake with or without Alkaline Hydrolysis and Subjected to Heat Treatment.

Jatropha curcas cake, a by-product of biodiesel production, is rich in protein and has potential to be used in livestock feed; however, the presence of antinutritional factors and phorbol esters limits its use. Thus, this study investigated toxicological and reproductive effects in male Wistar rats after subchronic exposure to J. curcas cake subjected to detoxification procedures. Rats were divided into seven groups (n = 10) and treated for 60 days. The control group received commercial feed, while experimental groups received a diet containing 5% J. curcas cake nonhydrolyzed or hydrolyzed with 5 M NaOH. The cakes were unwashed or washed with ethanol or water and were autoclaved at 121°C for 30 minutes. Alkaline hydrolysis combined with ethanol washing decreased the phorbol ester concentration in the cake by 98%. Histopathological findings included diffuse degeneration of the liver and edema around the pulmonary vessels in the nonhydrolyzed groups. In addition, nontreated females mated with males of nonhydrolyzed unwashed group showed a decreased number of live fetuses and an increased placental weight. There were no signs of toxicity in rats given hydrolyzed cakes washed and unwashed, indicating that alkaline hydrolysis associated with heat treatment is an efficient method for detoxification of the J. curcas cake.

Genotoxic potential of leaf extracts of Jatropha gossypiifolia L.

Jatropha gossypiifolia L. (Euphorbiaceae) is widely used in popular medicine. However, further toxicological studies are necessary for its reliable use. The present study aimed to evaluate the cytotoxic, genotoxic, and mutagenic effects of ethanolic and aqueous leaf extracts of J. gossypiifolia, using the test system Allium cepa. In addition, the phytochemical profile of the extracts was also obtained. Seeds of A. cepa were subjected to different concentrations of the two extracts (0.001, 0.01, 0.1, 1, and 10 mg/mL). Distilled water was used for the negative control and methyl methanesulfonate (4 x 10(-4) M) and trifluralin (0.84 ppm) for the positive controls. The values of mitotic index at all concentrations of ethanolic extract and at 0.1, 1, and 10 mg/mL aqueous extract showed a significant decrease. Alterations, such as chromosome adherence, C-metaphases, chromosome bridges, nuclear buds, and micronuclei were verified in both extracts but chromosome loss indicating genotoxic activity was observed only in the ethanolic extract. Presence of micronuclei on administration of the extracts, also indicated mutagenic action at the chromosome level. In the ethanolic extract, aneugenicity seemed to be the main activity, probably as a result of the action of terpenes and/or flavonoids, whereas in the aqueous extract, clastogenic action appeared to be the principal activity, presumably as a consequence of the effect of flavonoids and/or saponins. Thus, we suggest that the extracts of this species should be used with great caution for medicinal purpose.

Intoxicação experimental com as folhas de Jatropha gossypifolia (Euphorbiaceae) em ovinos / Experimental poisoning by the leaves of Jatropha gossypifolia (Euphorbiaceae) in sheep

As folhas recém-colhidas de Jatropha gossypifolia (Euphorbiaceae) foram letais para ovinos em administrações únicas de 40g/kg. A dose de 5g/kg não causou sintomas de intoxicação; as doses intermediárias provocaram a morte de parte dos animais. A evolução da intoxicação foi de 6 a 22 dias. O quadro clínico-patológico nos ovinos experimentais era caracterizado por perturbações digestivas, pulmonares, cardíacas e ainda alterações regressivas leves somente evidenciadas através de exames histológicos, hepáticas e renais. Esses achados são semelhantes aos observados em experimentos com as sementes de Jatropha curcas em caprinos, ovinos e bezerros, e com os com os frutos e as folhas de Jatropha glauca e Jatropha aceroides em caprinos, realizados por outros autores. Estas comparações indicam que, independentemente das espécies, as folhas de Jatropha spp. devem conter compostos semelhantes aos encontrados nas sementes.(AU)

Fresh green leaves of Jatropha gossypifolia (Euphorbiaceae) were lethal for sheep in single administrations of 40g/kg. The dose of 5g/kg did not cause poisoning, but intermediate doses caused death in part of the animals. The clinical course of poisoning was 6 to 22 days. The clinic and pathological picture in the experimental sheep was characterized by digestive, lung and heart disturbances, and also by slight microscopic liver and renal regressive alterations. These findings are similar to those observed in experiments with the seeds of Jatropha curcas in goats, sheep and calves, and with the fruits and leaves of Jatropha glauca and Jatropha aceroides in goats, performed by other authors. A comparison indicates that, independently of the plant species, the leaves of Jatropha spp. contain toxic compounds similar to those found in the seeds.(AU)

Intoxicação experimental com as folhas de Jatropha gossypifolia (Euphorbiaceae) em ovinos / Experimental poisoning by the leaves of Jatropha gossypifolia (Euphorbiaceae) in sheep

As folhas recém-colhidas de Jatropha gossypifolia (Euphorbiaceae) foram letais para ovinos em administrações únicas de 40g/kg. A dose de 5g/kg não causou sintomas de intoxicação; as doses intermediárias provocaram a morte de parte dos animais. A evolução da intoxicação foi de 6 a 22 dias. O quadro clínico-patológico nos ovinos experimentais era caracterizado por perturbações digestivas, pulmonares, cardíacas e ainda alterações regressivas leves somente evidenciadas através de exames histológicos, hepáticas e renais. Esses achados são semelhantes aos observados em experimentos com as sementes de Jatropha curcas em caprinos, ovinos e bezerros, e com os com os frutos e as folhas de Jatropha glauca e Jatropha aceroides em caprinos, realizados por outros autores. Estas comparações indicam que, independentemente das espécies, as folhas de Jatropha spp. devem conter compostos semelhantes aos encontrados nas sementes.

Fresh green leaves of Jatropha gossypifolia (Euphorbiaceae) were lethal for sheep in single administrations of 40g/kg. The dose of 5g/kg did not cause poisoning, but intermediate doses caused death in part of the animals. The clinical course of poisoning was 6 to 22 days. The clinic and pathological picture in the experimental sheep was characterized by digestive, lung and heart disturbances, and also by slight microscopic liver and renal regressive alterations. These findings are similar to those observed in experiments with the seeds of Jatropha curcas in goats, sheep and calves, and with the fruits and leaves of Jatropha glauca and Jatropha aceroides in goats, performed by other authors. A comparison indicates that, independently of the plant species, the leaves of Jatropha spp. contain toxic compounds similar to those found in the seeds.

Avaliação fitoterápica da Jatropha gossypiifolia L. na cicatrização de suturas na parede abdominal ventral de ratos / Phytotherapic evaluation of Jatropha gossypiifolia L. on rats ventral abdominal wall wound healing

INTRODUÇÃO: A espécie vegetal Jatropha gossypiifolia L., conhecida também como pião roxo, é utilizada na medicina popular como cicatrizante, anti-hipertensivo, purgativo e diurético. OBJETIVO: Avaliar a influência da administração intraperitoneal da Jatropha gossypiifolia L., na cicatrização de suturas da parede abdominal ventral de ratos, observando-se os seus aspectos macroscópicos, tensiométricos e microscópicos. MÉTODOS: Foram utilizados no procedimento 40 ratos da linhagem Wistar, machos, distribuídos em dois grupos de 20. Após incisão da parede e abertura da cavidade abdominal, foi instilado 1 ml/kg/peso de cloreto de sódio a 0,9 por cento no grupo controle e no grupo Jatropha o extrato bruto etanólico da Jatropha gossypiifolia L., na concentração de 1 ml/kg/ peso. Realizou-se a sutura da parede abdominal com fio de polipropileno, com pontos separados. Os animais foram avaliados na sua evolução pós-operatória e mortos em dois subgrupos, no 3º e 7º dia. Analisou-se a parede abdominal ventral macroscopicamente, mediu-se a força de resistência a tensão e foram estudados os aspectos histológicos do reparo cicatricial. RESULTADOS: No exame macroscópico encontraram-se aderências mais intensas nos subgrupos Jatropha no 3º e 7º dia. A avaliação tensiométrica foi significantemente maior nos subgrupos Jatropha no 3º e 7º dia. A avaliação histológica comparativa entre os subgrupos demonstrou que o processo inflamatório agudo foi significantemente maior no subgrupo Jatropha no 3º e 7º dia; a neoformação capilar foi significantemente maior no 3º dia pós-operatório do subgrupo Jatropha sendo os outros parâmetros histológicos semelhantes. CONCLUSÃO: O uso do extrato bruto de Jatropha gossypiifolia L. intraperitoneal não demonstrou melhora significativa no processo de cicatrização da sutura da parede abdominal ventral de ratos com a dose e concentração utilizadas.(AU)

INTRODUCTION: The Jatropha gossypiifolia L., which is used in popular medicine is considered to have good diuretic effect in hypertension and is also used as a laxative drug. It seems to have a healing effect, although not proved till now. PURPOSE: To evaluate the influence of intraperitoneum administration of Jatropha Gossypiifolia L., in suture healing of ventral abdominal wall of rats, through tensiometric measurement, macro and microscopic aspect of post-operative period. METHODS: Forty wistar male rates were allocated in two groups of 20 animals . After the incision and exposure of abdominal cavity 1 ml/kg/weight of 0,9 percent sodium chloride solution was injected in control group, and in the other one the injection was of 1 ml/kg/weight of a gross ethanol extract of Jatropha gossypiifolia L. The suture of the abdominal wall was than performed with polypropylene separated stitches. The animals were followed-up and killed in the third and seventh days. The ventral abdominal wall was macroscopically analyzed, the resistance strength to strain was measured and it was also studied the histological aspects. RESULTS: On macroscopic examination more intense adhesion was found on the group of Jatropha in both third and seventh post-operative days. The strain evaluation was meanly greater on Jatropha group also in third and seventh days. CONCLUSION: The histological comparative analysis between the different groups showed that the acute inflammatory process was meanly greater for the Jatropha group in third and seventh post-operative days. The vascular neoformation was significantly greater in third pos-operative day of Jathopha group; the other histological parameters were just alike. The intraperitoneum injection of Jatropha extract did not have any significant improvement for the wound healing on ventral abdominal wall on the evaluated animals in this study, no matter if analyzed at the third or seventh pos-operative days.(AU)

Estudo da cicatrização de suturas na bexiga urinária de ratos com e sem a utilização de extrato bruto de Jatropha gossypiifolia L. intraperitoneal / Healing process in bladder suture of rats with and without the administration of intraperitoneal Jatropha gossypiifolia L. gross extract

INTRODUÇÃO: A sutura dos tecidos e sua cicatrização é um dos fundamentos básicos da cirurgia e a procura de substâncias que melhorem este processo é desafio constante. O uso de substâncias retiradas de plantas tem sido testado há muitos anos, contudo sem ainda terem comprovação científica consolidada. OBJETIVO: Comparar as alterações macroscópicas e histológicas proporcionadas pelo uso do extrato bruto da Jatropha gossypiifolia L. intraperitonial, na cicatrização de suturas realizadas na bexiga urinária de ratos. MÉTODOS: Quarenta ratos da linhagem wistar, adultos, machos foram distribuídos em dois grupos, experimento e controle. Incisão longitudinal de 1cm na parede ventral da bexiga e síntese em plano único com pontos separados de poliglactina 910 5-0 (ethicon) foi realizada nos dois grupos. No controle, instilou-se na cavidade peritoneal água destilada na proporção de 1ml/kg de peso, enquanto no grupo Jatropha utilizou-se o extrato bruto de Jatropha gossypiifolia L. na proporção de 1ml/kg, que representava 200mg/kg de peso do fitoterápico. Cada grupo foi subdividido em dois subgrupos de 10 animais, sendo estes submetidos à eutanásia no 3º e 7º dia pós-operatório. Foi feita análise macroscópica e histológica comparativa entre os subgrupos. RESULTADOS: No 3º dia foi observada diferença estatisticamente significante nas variáveis inflamação aguda, neoformação vascular e colagenização, sendo a primeira, maior no grupo controle e as duas últimas no grupo Jatropha; no 7º dia as variáveis inflamação aguda e proliferação fibroblástica apresentaram-se mais intensas, com significado estatístico, no grupo controle. CONCLUSÃO: Não se observou efeito favorecedor cicatrizante do extrato bruto da Jatropha gossypiifolia L., intraperitonealmente aplicado, na bexiga urinária de ratos.(AU)

INTRODUCTION: The suture of tissues and their healing process is one of the basic fundamentals of surgery, and the research on substances which could improve the process is an ongoing challenge. The use of plants has been tested but till nowadays without scientific demonstration. PURPOSE: To compare the macroscopic and histological alterations done by the use of intraperitoneal Jatropha gossypiifolia L. gross extract, in the healing process of sutures performed on the bladder of rats. METHODS: Forty adult, male, Wister rats were distributed into two animal groups. One centimeter longitudinal incision on the bladder ventral wall, and single plane synthesis with separated polyglactine 910 5-0 (Ethicon) stitches was done in all the animals. In the control group an intraperitoneal cavity instillation of distilled water at a ratio of 1ml/kg/weight, and a 1ml/kg/weight of Jatropha gossypiifolia L. extract for the Jatropha group was done representing 200 mg of the substance. Each group was subdivided into two with 10 animals in each, being submitted to euthanasia on 3th and 7th post-operative days. Comparative histological, macroscopic and statistical analysis were undertaken between the subgroups. RESULTS: Statistical significant difference was observed in the acute inflammation changes, vascular neoformation and bonding on day 3; the first one was greater in the control group, and the latter two greater in the Jatropha group; acute inflammation variables and fibroblastic proliferation presented to be more intense on day 7, with statistical significance favoring the control group. CONCLUSION: No favorable healing effect was observed with the administration of single intraperitoneal dose of Jatropha gossypiifolia L. gross extract on the sutures of bladder in rats.(AU)