Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Hoodia gordonii à uma planta da famÃlia das apocinÃceas. OriginÃria do sudeste da Ãfrica, onde tem sido historicamente usada para suprimir o apetite durante longas jornadas de caÃa, sendo utilizada em diversos paÃses com o objetivo de emagrecer. No Brasil foi retirada do mercado devido à falta de estudos que comprovem sua eficÃcia e seguranÃa para o uso. O objetivo deste trabalho foi avaliar as alteraÃÃes comportamentais, neuroquÃmicas e glicolipÃdicas em ratos tratados com Hoodia gordonii. Para a realizaÃÃo deste estudo H. gordonii foi administrada por via oral nas doses de 25 e 50 mg/Kg durante oito dias consecutivos em ratos Wistar machos (160-200g), D-anfetamina 2 mg/Kg foi administrada intraperitonealmente de forma aguda e usada como padrÃo positivo. Os testes aconteceram 60 minutos apÃs o ultimo dia de tratamento com a Hoodia e 30 minutos apÃs o tratamento com D-anfetamina. Foram avaliados a variaÃÃo de peso dos animais durante o tratamento, bem como o consumo de Ãgua e comida. Para os testes comportamentais foram feitos os testes de labirinto em cruz elevado, campo aberto e placa perfurada. Para os estudos neuroquÃmicos foi feito HPLC com detecÃÃo eletroquÃmica. Para os testes glicolipÃdicos foi feita dosagem de Glicose, HDL, LDL, TG, colesterol total, ALT e AST. Os resultados mostraram que H. gordonii à capaz de reduzir o ganho de massa corpÃrea, bem como reduzir o consumo de comida e Ãgua. Os resultados dos testes comportamentais mostraram que ela à capaz de reduzir os parÃmetros observados no teste do labirinto em cruz e placa perfurada sem mostrar alteraÃÃo significante no campo aberto. Os resultados dos experimentos neuroquÃmicos evidenciaram um aumento do conteÃdo de noradrenalina e dopamina em corpo estriado de ratos, detectados eletroquimicamente pelo HPLC. Nos testes bioquÃmicos foi visto que ela tem a capacidade de reduzir os nÃveis de glicose, bem como a concentraÃÃo de triglicerÃdeos e colesterol total em soro de ratos, sem mostrar alteraÃÃo significante da ALT e AST. Foi possÃvel concluir que H. gordonii à capaz de reduzir a ingestÃo de alimentos e que este efeito pode estar de alguma forma ligado à neurotransmissÃo noradrenÃrgica e dopaminÃrgica, possuindo tambÃm atividade ansiogÃnica evidenciada pelos estudos comportamentais. / Hoodia gordonii is a plant of the family apocinaceae. Originally from southeastern Africa, where it has historically been used to suppress appetite during long hunting trips, being used in several countries in order to lose weight. In Brazil was withdrawn from the market due to lack of studies proving its efficacy and safety for use. The aim of this study was to evaluate the behavioral changes and neurochemical glicolipÃdicas in rats treated with Hoodia gordonii. For this study H. gordonii was administered orally at doses of 25 and 50 mg/kg for eight consecutive days in male Wistar rats (160-200g), D-amphetamine 2 mg/kg was intraperitoneally administered acutely and used as a positive standard. The tests took place 60 minutes after the last day of treatment with the Hoodia and 30 minutes after treatment with D-amphetamine. We evaluated the weight change of the animals during treatment, as well as the consumption of water and food. For behavioral tests were performed tests elevated plus-maze, open field and hole board. For neurochemical studies was done HPLC with electrochemical detection. For testing was done glycolipid glucose, HDL, LDL and TG, total cholesterol, ALT and AST. The results showed that H. gordonii is capable of reducing body mass gain and reduce the consumption of food and water. The results of behavioral tests showed that it is able to reduce the parameters observed in the plus-maze test and hole board showing no significant change in the open field. The results of experiments showed an increase in the neurochemical content of noradrenaline and dopamine in the striatum of rats electrochemically detected by HPLC. In biochemical tests it was seen that it has the ability to lower blood glucose levels as well as the concentration of triglycerides and total cholesterol in serum from mice, showing no significant change in ALT and AST. It was concluded that H. gordonii is able to reduce food intake, and this effect may be somehow linked to the dopaminergic and noradrenergic neurotransmission, having also anxiogenic activity evidenced by behavioral studies.

Thesis (Bsc. (Animal production)) --University of Limpopo, 2009. / Two experiments were conducted to evaluate the effect of Hoodia gordonii meal supplementation at finisher stage on productivity and carcass characteristics of Ross 308 broiler chickens. Experiment 1 examined the effect of levels of Hoodia gordonii meal supplementation of grower diet fed to Ross 308 broiler chickens at the finisher stage (30 – 42 days of age) on productivity and carcass characteristics in a 12 day experimental period. The experiment was a completely randomized design with a 2 (two sexes of chickens) x 6 (levels of Hoodia gordonii meal [0, 100, 200, 300, 400 or 500 mg]) factorial arrangement of treatments in which three hundred and sixty broiler chickens at finisher stage were randomly allocated to twelve treatments with three replicates of ten birds each. Level of Hoodia gordonii meal supplementation had no effect (P>0.05) on diet intake, intake as percentage of live weight, growth rate, feed conversion ratio, live weight at 42 days of age and mortality of broiler chickens at finisher stage. All carcass characteristics were not affected (P>0.05) by the treatments except fat pads. Chickens given a daily dose of 300 mg of Hoodia gordonii meal had lower (P<0.05) fat pad weights than unsupplemented ones. Male broiler chickens had higher (P<0.05) feed intake and heavier drum sticks than female broiler chickens. Experiment 2 examined the effect of Hoodia gordonii meal dose interval at finisher stage in a 2 (two sexes of chickens) x 3 (dosage intervals) factorial, complete randomized design that involved three hundred and sixty chickens that were randomly allocated to six treatments with six replicates of ten birds each. Broiler chickens were fed either a grower diet without Hoodia gordonii meal; grower diet with 300 mg of Hoodia gordonii meal/ bird supplemented everyday for 12 days; or grower diet with 300 mg of Hoodia gordonii meal/ bird supplemented twice, on 30th and 36th days of age. Hoodia gordonii meal dose interval had no effect (P>0.05) on dry matter feed intake, intake as percentage of live weight, growth rate, live weight at 42 days of age, feed conversion ratio, mortality and all carcass characteristics except fat pad of broiler chickens. Daily dosing with 300 mg of Hoodia gordonii meal/ bird reduced (P<0.05) fat pad weights of broiler chickens by 18 percentage points. Male broiler chickens had higher (P<0.05) feed intake, nitrogen digestibility, nitrogen retention and live weight than female broiler chickens. It is concluded that chickens given a daily supplement of 300 mg of Hoodia gordonii meal had lower fat pad weights than unsupplemented ones. This could not be explained in terms of differences in feed intake, digestibility, or growth rate.

Les travaux décrits dans ce mémoire ont pour objet la synthèse d'un glycostéroïde appelé P57 isolé d'une plante succulente du nom de Hoodia gordonii présentant des propriétés anti-appétantes. La première partie de ce travail décrit la synthèse de la hoodigogénine A, aglycone du P57. La synthèse mise au point comprend comme étape clef une réaction de Norrish type I couplée à une réaction de Prins conduisant à l'introduction de la fonction hydroxyle en position 14β au départ de 12-oxo stéroïdes. L'étude réalisée a permis de montrer que la formation des diols 12β-14β ne dépendaient pas de la nature de la jonction des cycles A et B, mais de celle du substituant en position 20. Ainsi, il a été possible de réaliser la première synthèse de la hoodigogénine A en 13 étapes avec un rendement global de 3% au départ de la 3α-12α-diacétoxypregnanone mais également de trois analogues de la hoodigogénine A. La deuxième partie de ces travaux a porté sur la synthèse totale de 14β-hydroxy-androstanes. La méthodologie mise en oeuvre est basée sur une réaction tandem de Michael-aldol initiée par TiCl4 qui permet d'accéder efficacement à un dérivé bicyclique représentant les cycles C et D présents dans les stéroïdes. En généralisant cette réaction tandem, des dérivés de type diquinanes, hydrindanes et décalines ont pu être obtenus. La transformation d'un dérivé hydrindénone adéquatement fonctionnalisé en diène 1,3 suivie d'une réaction de Diels-Alder a permis la synthèse d'un premier dérivé tétracyclique 14β-hydroxylé. Deux autres dérivés tétracycliques ont également pu être préparés, au départ d'une hydrindiénone en combinant une réaction de Michael avec une annélation de type Robinson.

Les travaux décrits dans ce mémoire ont pour objet la synthèse d’un glycostéroïde appelé P57 isolé d'une plante succulente du nom de Hoodia gordonii présentant des propriétés anti-appétantes. La première partie de ce travail décrit la synthèse de la hoodigogénine A, aglycone du P57. La synthèse mise au point comprend comme étape clef une réaction de Norrish type I couplée à une réaction de Prins conduisant à l'introduction de la fonction hydroxyle en position 14β au départ de 12-oxo stéroïdes. L’étude réalisée a permis de montrer que la formation des diols 12β-14β ne dépendaient pas de la nature de la jonction des cycles A et B, mais de celle du substituant en position 20. Ainsi, il a été possible de réaliser la première synthèse de la hoodigogénine A en 13 étapes avec un rendement global de 3% au départ de la 3α-12α-diacétoxypregnanone mais également de trois analogues de la hoodigogénine A. La deuxième partie de ces travaux a porté sur la synthèse totale de 14β-hydroxy-androstanes. La méthodologie mise en oeuvre est basée sur une réaction tandem de Michael-aldol initiée par TiCl4 qui permet d'accéder efficacement à un dérivé bicyclique représentant les cycles C et D présents dans les stéroïdes. En généralisant cette réaction tandem, des dérivés de type diquinanes, hydrindanes et décalines ont pu être obtenus. La transformation d'un dérivé hydrindénone adéquatement fonctionnalisé en diène 1,3 suivie d'une réaction de Diels-Alder a permis la synthèse d'un premier dérivé tétracyclique 14β-hydroxylé. Deux autres dérivés tétracycliques ont également pu être préparés, au départ d’une hydrindiénone en combinant une réaction de Michael avec une annélation de type Robinson. / This thesis is dealing with the synthesis of a glycosteroid named P57 extracted from Hoodia gordonii, a succulent plant known for its appetite suppressant properties. The first part of this work describes the synthesis of the hoodigogenin A, the aglycon of the P57. The key step of this synthesis was a Norrish type I reaction combined with a Prins reaction leading to the introduction of a 14β-hydroxyl function starting from the corresponding 12-keto steroids. The studies showed that the A/B ring junction has no influence on the Norrish type I-Prins reaction but that the substitution pattern at position 20 is important. Thus, the synthesis of the hoodigogenin A was realized for the first time in 13 steps with 3% global yield starting from the 3α-12α-diacetoxypregnanone and this methodology also allowed us to synthesize three analogs of the hoodigogenin A. The second part deals with the total synthesis of 14β-hydroxy-androstanes. In order to access to a bicyclic derivative representing cycles C and D of steroids, we worked on an intramolecular Michael-aldol reaction promoted by TiCl4. The extension of this Michael-aldol reaction afforded very efficiently a large variety of polyfunctionalized 5-5, 5-6 and 6-6 fused ring systems. Then, a Diels-Alder reaction from a 1,3- diene obtained from a hydrindenon derivative led us to a first tetracyclic compound bearing a 14β-hydroxyl function. Finally, two other tetracyclic derivatives had been obtained by a Michael reaction followed by a Robinson reaction.