An appetite suppressant from Hoodia species

Studies conducted at the Council for Scientific and Industrial Research (CSIR, South Africa) identified extracts from Hoodia species, in particular Hoodia pilifera and Hoodia gordonii, as possessing appetite suppressing properties. Two pregnane glycosides were isolated by fractionation of the dried stems of H. gordonii. Their structures were determined as 3beta-[beta-D-thevetopyranosyl-(1-->4)-beta-D- cymaropyranosyl-(1-->4)-beta-D-cymaropyranosyloxy]-12beta-tigloyloxy-14beta-hydroxypregn-5-en-20-one (1) and 3beta-[beta-D-cymaropyranosyl-(1-->4)-beta-D-6-thevetopyranosyl-(1-->4)-beta-D-cymaropyranosyl-(1-->4)-beta-D-cymaropyranosyloxy]-12beta-tigloyloxy-14beta-hydroxypregn-5-en-20-one (2) on the basis of spectroscopic studies and conversion to known compounds. Compounds 1 and 2 were also isolated from H. pilifera. Compound 1 was tested for its appetite suppressant properties in rats by oral gavage at 6.25-50 mg/kg and the results showed that all doses resulted in a decrease of food consumption over an eight day period and a body mass decrease when compared to the control sample receiving only the vehicle. In a comparative study against a fenfluramine control sample, compound 1 resulted in a reduction in food intake over the study period, with a concomitant overall decrease in body weight while fenfluramine resulted in a small decrease in food intake, but an increase in body weight (though less than control group) over the same period of time.     

Metabolic effect of short term administration of Hoodia gordonii,an herbal appetite suppressant

Hoodia gordonii (family: Apocynaceae) is used traditionally by the Khoi-San tribes to control hunger. It has become extremely popular and has triggered commercial interest due to its appetite suppressant property. The present study was undertaken to investigate the appetite regulatory mechanism and associated metabolic changes induced by the herb. Effect of organic solvent extract of H. gordonii on food intake and body weight of male Sprague Dawley rats was monitored at three different doses 50, 100 and 150 mg/kg body weight, given orally for five days. Subsequently, the dose of 100 mg/kg body weight was selected for further studies on the regulatory hormones and biochemical variables. Dose-dependent reduction in food intake (12–26%) was observed at a dose of 100 and 150 mg/kg body weight (p < 0.05). Appetite suppression persisted for 6 h and food intake was restored within 24 h after stopping of the treatment. There was an increase in liver glycogen stores, activity of mitochondrial CPT-1 and thyroid hormones in treated animals. The circulating levels of NPY and IGF-1 were decreased with marginal increase in leptin and CCK, in case of treated rats. There was no change in blood glucose and insulin levels were not affected significantly. The hormonal and metabolic changes due to treatment with the H. gordonii extract may be responsible for its anorectic activity.     

New oxypregnane glycosides from appetite suppressant herbal supplement Hoodia gordonii

Hoodigosides A-K (1-11), eleven new oxypregnane glycosides and a previously reported oxypregnane glycoside P57AS3 were isolated from the aerial parts of Hoodia gordonii. The structures of these 12-O-beta-tigloyl isoramanone glycosides were determined on the basis of chemical evidence and extensive spectroscopic methods that include one-dimensional and two-dimensional NMR. Cytotoxicity and antioxidant activities of these compounds were tested in cell based assays where they were found to be inactive.     

Synthesis of Hoodigogenin A, aglycone of natural appetite suppressant glycosteroids extracted from Hoodia gordonii

14β-hydroxy pregnane glycosides extracted from Hoodia gordonii, a succulent plant isolated from Apocynaceae are suggested to have appetite suppressant properties in animals and humans. However, limited reports on biological studies concerning the appetite suppressant properties are available in the open literature. One reason for that is the poor availability of these glycosteroids because H. gordonii is a protected plant and the yield of extraction lies between 0.003% and 0.02%. Starting from 3α,12α-diacetoxy-pregnanone 1, we disclose in this report the synthesis of Hoodigogenin A, the aglycone of the natural 14β-hydroxy pregnane glycosides extracted from H. Gordonii.     

Synthesis and appetite suppressant activity of 1-aryloxy-2-substituted aminomethyltetrahydronaphthalenes as conformationally rigid analogues of fluoxetine

Several 1-aryloxy-2-substituted aminomethyltetrahydronaphthalenes (7-21) as conformationally rigid analogues of fluoxetine were synthesized and evaluated for their anorexigenic and antidepressant activities. For SAR studies the related acyclic analogues (22-27) were also prepared. Out of the 21 synthesized compounds, 10 compounds (9, 10, 11, 15, 16, 18, 21, 22, 23 and 27) exhibited significant anorexigenic activity (at 75 micromol/kg). Interestingly, all the compounds (7-20, 22-26) were devoid of antidepressant effect, except for compounds 21 and 27 in which the antidepressant activity was retained. Compound 16 emerged as the most active compound of the series with better anorexigenic activity (97.92%) compared to fluoxetine (76.25%) and even with a clinically used drug sibutramine, thus providing a new structural lead for appetite suppressants.     

Murine transfer factor. III. Specific interactions between transfer factor and antigen

The interactions between dialyzable transfer factor and antigens have been studied. Incubation of transfer factor-containing dialysates from ferritin-sensitized mice or ferritin-coated plastic surfaces removed the antigen-sensitizing activity; incubations of the same preparations on cytochrome c-coated surfaces did not. Similar results were obtained when cytochrome c-transfer factor was studied. Incubation on cytochrome c-coated surfaces removed the activity, but incubation on ferritin-coated surfaces did not. Specific transfer factor activities could be recovered by elution with 8 M urea or acetonitrile. The finding of interactions between transfer factor and antigens provides evidence for a molecular basis of the specificity of the immunologic effects of transfer factor. This technique may also enable us to obtain amounts of specific material that are adequate for chemical analysis.     

Human transfer factor. II. Clinical results with the large pool transfer factor

21 patients with diseases due to immunological causes were treated 6 times at an interval of four weeks by administering 5 E TF or 1 E TF each per 10 kg of body weight. TF consisted of 5 different large pool TF charges of 420 to 822 buffy-coats of fresh stored whole blood. Clinical and immunological investigations as well as biochemical ones in the laboratory were made before and after treatment. Large pool TF is clinically effective in 9 from 18 patients and immunologically in 16 from 18 patients. There is a greater effect in immunodeficiencies than in autoimmune diseases. TF is not able to remove the defect for a long time. Repeated administrations are required. TF therapy may be regarded as a substitution therapy. At first, the intervals have to be chosen according to clinical parameters (recidive of the disease or crisis respectively). There is a good compatibility of TF. Side-effects could not be observed. The frequent immunological conversions after score evaluation indicate, however, that in comparison to the clinical appearance the course of the disease must be seen to be much more complex than it can be expressed by in vitro correlates of immunological responses. Statistically ensured correlations of single tests concerning the clinical course could also not be found. Large pool TF provides favourable conditions for controlled therapy trials in order to elucidate those findings of therapy which hitherto had been a subject of controversy (e.g. autoimmune diseases, tumours).     

Episome-mediated transfer of drug resistance in Enterobacteriaceae. IX. Recombination of an R factor with F

Watanabe, Tsutomu (Keio University, Tokyo, Japan), and Chizuko Ogata. Episome-mediated transfer of drug resistance in Enterobacteriaceae. IX. Recombination of an R factor with F. J. Bacteriol. 91:43-50. 1966.-R factors can be transduced in Salmonella typhimurium with phage P-22, and a majority of the drug-resistant transductants are unable to transfer their drug resistance by cell-to-cell contact, as we have previously reported. Several exceptional types of transductants of S. typhimurium, with the markers of resistance to sulfonamide, streptomycin, and chloramphenicol, were recently obtained by transduction with phage P-22 of a four-drug-resistance R factor carrying the markers of resistance to sulfonamide, streptomycin, chloramphenicol, and tetracycline. They were exceptional in that they had low conjugal transferability of their drug resistance. When one of these exceptional transductants (38R) was transferred to an F(+) strain of Escherichia coli K-12, 38R acquired high transferability in its further transfer. This high transferability was found to be due to the recombination of 38R with F. Transductant 38R was of the fi(+) (fi = fertility inhibition) type, and did not show superinfection immunity against fi(+) and fi(-) R factors. The recombinant 38R.F was genetically very stable and resistant to elimination with acridines. It did not show superinfection immunity against fi(+) and fi(-) R factors, but did show superinfection immunity against F. Further, 38R.F did not restrict a female-specific phage (W-31), unlike wild-type F. F(-) and R(-) segregants were isolated from this recombinant 38R.F, and these segregants exhibited genetic characteristics different from the original R, its transductant 38R, and wild-type F.     

Passive transfer of cell-mediated immunity in xenogeneic animals

Cell-mediated immunity (delayed hypersensitivity) to 1-chloro-2,4-dinitrobenzene (DNCB) was passively transferred from sensitized guinea pigs to mice. Transfer was accomplished by subcutaneous injection of peritoneal exudate cells of sensitized guinea pigs.     

Immunity to exoerythrocytic forms of malaria. II. Passive transfer of immunity to exoerythrocytic forms

The passive transfer of heat-inactivated or nonheat-inactivated convalescent serum, from turkeys inoculated with Plasmodium fallax exoerythrocytic forms and treated with chloroquine to suppress the development of erythrocytic forms and the development of immunity to them, delayed the exoerythrocytic-form infection in turkeys inoculated intravenously with exoerythrocytic forms. The degree of exoerythrocyticform parasitization in cerebral tissue was significantly less in the experimental groups than the degree of parasitization in control groups, and the experimental birds continued gaining weight for a longer period than the control birds. The passive transfer of immune serum had an effect on the course of the exoerythrocytic-form infection equivalent to killing 90% of the exoerythrocytic-form inoculum. The immunity to exoerythrocytic forms is form-specific, since the infected, chloroquine-treated, serum donors were just as susceptible to an erythrocytic-form challenge infection as normal turkeys.In vitro studies demonstrated that heat-inactivated serum from turkeys immune to exoerythrocytic-form infections caused a precipitate to form at the small end of exoerythrocytic merozoites. This precipitate was not observed on merozoites mixed with control serum.