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Use of gelatin-acacia coacervate containing benzocaine in topical formulations.

The in vitro release of a drug from topical formulations depends on the concentration of the drug in the formulation, the solubility of the drug in the base, the diffusion coefficient of the drug in the vehicle, and the partition coefficient of the drug between the vehicle, and the release medium. Incorporation of both complexing agents and cosolvents into such formulations has been used to enhance the in vitro release of a drug from topical formulations. In this investigation, a novel approach to enhance the in vitro release of benzocaine from different ointment formulations has been introduced. In this study, benzocaine was microencapsulated using gelatin-acacia complex coacervation technique. Various weight fractions of the coacervate, 5, 10, and 20% (w/w), were incorporated into both oleaginous and absorption bases. The in vitro release characteristics of benzocaine from the resulting ointments were studied using a modified USP Dissolution Apparatus 2. A plot of the cumulative amount of drug released (7-8%) per unit surface area versus (time)(1/2) was linear. Microscopic studies of the formulations revealed that the coacervates maintained their integrity in the formulation during the preparation and storage of the dosage form. Differential scanning calorimetric (DSC) studies indicated that the drug existed in the crystalline state in all formulations including those at a low drug load (0.5% w/w). DSC was also used to determine the solubility of the drug in the formulation. The rate and extent of drug release was higher in the absorption base as compared to the oleaginous base.

Administration, Topical↗

Kinmoonosides A-C, three new cytotoxic saponins from the fruits of Acacia concinna, a medicinal plant collected in myanmar.

Three genuine saponins, named kinmoonosides A-C (1-3), have been isolated, together with a new monoterpenoid (4), from a methanolic extract of the fruits of Acacia concinna. The structures of kinmoonosides A-C were elucidated on the basis of spectral analysis as 3-O-¿alpha-L-arabinopyranosyl(1-->6)-[beta-D-glucopyranosyl(1-->2) ]-b eta-D-glucopyranosyl¿-21-O-¿(6R, 2E)-2-hydroxymethyl-6-methyl-6-O-[4-O-(2'E)-6'-hydroxyl-2'-hydroxymet hyl-6'-methyl-2',7'-octadienoyl-beta-D-quinovopyranosyl]-2, 7-octadienoyl¿acacic acid 28-O-alpha-L-arabinofuranosyl(1-->4)-[beta-D-glucopyranosyl(1-->3)]-a lpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester (1); 3-O-¿alpha-L-arabinopyranosyl(1-->6)-[beta-D-glucopyranosyl(1-->2) ]-b eta-D-glucopyranosyl¿-21-O-¿(6S, 2E)-2-hydroxymethyl-6-methyl-6-O-[4-O-(2'E)-6'-hydroxyl-2'-hydroxymet hyl-6'-methyl-2',7'-octadienoyl-beta-D-quinobopyranosyl]-2, 7-octadienoyl¿acacic acid 28-O-alpha-L-arabinofuranosyl(1-->4)-[beta-D-glucopyranosyl(1-->3)]-a lpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester (2); and 3-O-¿alpha-L-arabinopyranosyl(1-->6)-[beta-D-glucopyranosyl(1-->2) ]-b eta-D-glucopyranosyl¿-21-O-[(2E)-6-hydroxyl-2-hydroxymethyl-6-methyl- 2,7-octadienoyl]acacic acid 28-O-alpha-L-arabinofuranosyl(1-->4)-[beta-D-glucopyranosyl(1-->3)]-a lpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester (3), respectively. The new monoterpenoid 4 was determined as 4-O-[(2E)-6-hydroxyl-2-hydroxymethyl-6-methyl-2, 7-octadienoyl]-D-quinovopyranose. Compounds 1-3 showed significant cytotoxicity against human HT-1080 fibrosarcoma cells.

Antineoplastic Agents, Phytogenic↗

Butyrate modulates TGF-beta1 generation and function: potential renal benefit for Acacia(sen) SUPERGUM (gum arabic)?

Anecdotal evidence suggests that high fibre supplementation of dietary intake may have health benefits in renal disease related to alterations in circulating levels of short-chain fatty acids. The aim of the study was to examine the hypothesis that dietary manipulation may increase serum butyrate and thus have potential beneficial effects in renal disease. We examined the effect of dietary supplementation with a gum arabic sample of standardized molecular characteristics, Acacia(sen) SUPERGUM EM2 (SUPERGUM), on systemic levels of butyrate in normal human subjects. In an in vitro study, we also examined the potential role of butyrate in modifying the generation of the profibrotic cytokine transforming growth factor-beta (TGF-beta1) by renal epithelial cells. Following 8 weeks of dietary supplementation with 25 g/day of SUPERGUM, there was a two-fold increase in serum butyrate (n=7, P=0.03). In vitro work demonstrated that exposure of renal epithelial cells to elevated concentrations of butyrate suppressed both basal and stimulated TGF-beta1 synthesis. The action of butyrate was mediated by suppression of the extracellular signal-regulated kinase/mitogen-activated protein kinase signalling pathway. In addition, butyrate exposures reduced the response of renal epithelial cells to TGF-beta1 as assessed by luciferase activity of a TGF-beta-responsive reporter construct. Attenuation of TGF-beta1 signalling was associated with reduced phosphorylation of Smad 3 and decreased trafficking of TGF-beta1 receptors into signalling, non-lipid raft-associated membrane fractions. In conclusion, the data demonstrate that dietary supplementation with SUPERGU increased serum butyrate, which at least in vitro has beneficial effects on renal pro-fibrotic cytokine generation.

Butyrates↗

Avicins: triterpenoid saponins from Acacia victoriae (Bentham) induce apoptosis by mitochondrial perturbation.

Anticancer agents target various subcellular components and trigger apoptosis in chemosensitive cells. We have recently reported the tumor cell growth inhibitory properties of a mixture of triterpenoid saponins obtained from an Australian desert tree (Leguminosae) Acacia victoriae (Bentham). Here we report the purification of this mixture into two biologically pure components called avicins that contain an acacic acid core with two acyclic monoterpene units connected by a quinovose sugar. We demonstrate that the mixture of triterpenoid saponins and avicins induce apoptosis in the Jurkat human T cell line by affecting the mitochondrial function. Avicin G induced cytochrome c release within 30-120 min in whole cells and within a minute in the cell-free system. Caspase inhibitors DEVD or zVAD-fmk had no effect on cytochrome c release, suggesting the direct action of avicin G on the mitochondria. Activation of caspase-3 and total cleavage of poly(ADP-ribose) polymerase (PARP) occurred between 2 and 6 h posttreatment with avicins by zVAD-fmk. Interestingly, in the treated cells no significant changes in the membrane potential preceded or accompanied cytochrome c release. A small decrease in the generation of reactive oxygen species (ROS) was measured. The study of these evolutionarily ancient compounds may represent an interesting paradigm for the application of chemical ecology and chemical biology to human health.

Apoptosis↗

Specifications for gum arabic (Acacia senegal); analytical data for samples collected between 1904 and 1989.

The regulatory specifications for gum arabic (Acacia senegal) are superficial and inadequate to ensure that it is not adulterated with non-permitted gums from other botanical sources. Moreover, the existing specifications do not give the consumer the essential assurance, fundamental to food safety evaluation principles, that the nature and quality of gum arabic used in foodstuffs always conforms to that of the Test Article selected for the toxicological studies which justified the current status ('ADI not specified') of gum arabic as a permitted food additive. The availability of well-preserved gum arabic samples, collected between 1904 and 1939, has enabled invaluable data to be added to those derived from samples from the most recent crops. The resulting analytical data substantiate and greatly extend the quantitative information available previously for the chemical characterization of gum arabic for regulatory and trade purposes. The data confirm that good-quality commercial gum arabic was used previously as the Test Article. There is no evidence that the specific rotation of gum arabic has become significantly less negative in recent years.

Amino Acids↗

Gum arabic (Acacia senegal): unambiguous identification by 13C-NMR spectroscopy as an adjunct to the Revised JECFA Specification, and the application of 13C-NMR spectra for regulatory/legislative purposes.

The JECFA Specification for gum arabic was revised in 1990 to reflect more closely the specification of the Test Article used in evaluations that led to its classification 'ADI not specified' in 1982/83. Some producers and traders have objected to the Revised Specification; in contrast, consumer-protection groups consider that it remains too lax to provide the degree of safety assurance expected. This paper presents analytical data that confirm the mean values previously established for nitrogen and the specific rotation of bulk commercial gum arabic from Acacia senegal. The data also establish that natural gum arabic imported into the USA and Europe in 1989/91 met the Revised Specification, but that a disturbingly high proportion of spray-dried, processed gums sold as 'gum arabic' did not. NMR spectroscopy has (a) indicated that some such samples are based on non-permitted gums and (b) confirmed that the 1983 Test Article represents not only typical 1990/91 shipments but also a wide range of reference gum arabic samples from other reputable sources. Details of a representative 13C-NMR spectrum, derived by averaging the relative intensities for the characteristic resonances of 35 gum arabic samples, are given for future regulatory/legislative purposes. Some limitations of the Revised Specification and its susceptibility to commercial exploitation are discussed.

Carbon Isotopes↗

Acacia gum (Gum Arabic): a nutritional fibre; metabolism and calorific value.

Gum Arabic (Acacia gum, INS 414: E414) is extensively used as a food additive, but there is no regulatory or scientific consensus about its calorific value. It is a complex polysaccharide, primarily indigestible to both humans and animals, not degraded in the intestine, but fermented in the colon under the influence of microorganisms. Despite a range of animal studies, there are no usable data for humans which can quantify the utilizable energy of Gum Arabic. Estimates in the literature from animal experiments vary from 0 to 4 kcal/g. After certain allowances are made for the energy losses from volatile and gaseous fermentation products, an upper level of 2 kcal/g for rats has been set. The situation in man is demonstrably different, with greatly reduced amounts of such products, and the need to adapt for varying periods before Gum Arabic is attacked by colonic bacteria. In the absence of an agreed scientific assignment, the FDA in the USA insist upon 4 kcal/g in nutritional labelling, whereas in Europe, no value has been assigned to soluble dietary fibre, such as Gum Arabic. This review argues that based on present scientific knowledge only an arbitrary value can be used for regulatory purposes.

Animals↗

Canopy development and solar conversion efficiency in Acacia auriculiformis under drought stress.

A glasshouse experiment was performed with Acacia auriculiformis seedlings to investigate the effects of decreased soil water potential on phyllode extension, abscission and solar conversion efficiency, e. Six-month-old seedlings were subjected for 39 days to one of four treatments: well watered (soil water potential maintained above -0.5 MPa), moderately drought stressed (soil water potential maintained above -1.5 MPa), severely drought stressed (soil water potential maintained above -2.5 MPa) and well watered but pruned to maintain a leaf area approximating that of the severely drought-stressed treatment. Aboveground biomass accumulation decreased by 21% below that of the well-watered controls in the moderately drought-stressed seedlings and by 47% in the severely drought-stressed seedlings as a result of both decreased interception of solar radiation and lower e. Differences in phyllode extension rate, rather than in phyllode abscission, were primarily responsible for the differences in interception of solar radiation among treatments. Decreases in phyllode extension rate and water use occurred simultaneously in response to decreasing soil water potential. Specific leaf area decreased and water use efficiency increased in response to drought stress.

Journal Article↗

Leaf physiology, production, water use, and nitrogen dynamics of the grassland invader Acacia smallii at elevated CO(2) concentrations.

Invasion by woody legumes can alter hydrology, nutrient accumulation and cycling, and carbon sequestration on grasslands. The rate and magnitude of these changes are likely to be sensitive to the effects of atmospheric CO(2) enrichment on growth and water and nitrogen dynamics of leguminous shrubs. To assess potential effects of increased atmospheric CO(2) concentrations on plant growth and acquisition and utilization of water and nitrogen, seedlings of Acacia smallii Isely (huisache) were grown for 13 months at CO(2) concentrations of 385 (ambient), 690, and 980 micro mol mol(-1). Seedlings grown at elevated CO(2) concentrations exhibited parallel declines in leaf N concentration and photosynthetic capacity; however, at the highest CO(2) concentration, biomass production increased more than 2.5-fold as a result of increased leaf photosynthetic rates, leaf area, and N(2) fixation. Measurements of leaf gas exchange and aboveground biomass production and soil water balance indicated that water use efficiency increased in proportion to the increase in atmospheric CO(2) concentration. The effects on transpiration of an accompanying decline in leaf conductance were offset by an increase in leaf area, and total water loss was similar across CO(2) treatments. Plants grown at elevated CO(2) fixed three to four times as much N as plants grown at ambient CO(2) concentration. The increase in N(2) fixation resulted from an increase in fixation per unit of nodule mass in the 690 micro mol mol(-1) CO(2) treatment and from a large increase in the number and mass of nodules in plants in the 980 micro mol mol(-1) CO(2) treatment. Increased symbiotic N(2) fixation by woody invaders in response to CO(2) enrichment may result in increased N deposition in litterfall, and thus increased productivity on many grasslands.

Journal Article↗

Mating-type locus control of killer toxins from Kluyveromyces lactis and Pichia acaciae.

Killer-toxin complexes produced by Kluyveromyces lactis and Pichia acaciae inhibit cell proliferation of Saccharomyces cerevisiae. Analysis of their actions in haploid MATalpha cells revealed that introduction of the opposite mating-type locus (MATa) significantly suppressed antizymosis. Together with resistance expressed by MATa/MATalpha diploids, the reciprocal action of MATa or MATalpha in haploids of opposite mating types suggests that these killer toxins may be subject to MAT locus control. Congruently, derepressing the silent mating-type loci, HMR and HML, by removing individual components of the histone deacetylase complex Sir1-4, either by transposon-tagging or by chemically inactivating the histone deacetylase catalytic subunit Sir2, yields toxin resistance. Consistent with MAT control of toxin action, killer-toxin-insensitive S. cerevisiae mutants (kti) become mating-compromised despite resisting the toxins' cell-cycle effects. Mating inhibition largely depends on the time point of toxin application to the mating mixtures and is less pronounced in Elongator mutants, whose resistance to the toxins' cell-cycle effects is the result of toxin-target process deficiencies. In striking contrast, non-Elongator mutants defective in early-response events such as toxin import/activation hardly recover from toxin-induced mating inhibition. This study reveals a novel effect of yeast killer toxins on mating and sexual reproduction that is independent of their impact on cellular proliferation and cell-cycle progression.

Genes, Mating Type, Fungal↗

Bradyrhizobium Populations Occur in Deep Soil under the Leguminous Tree Acacia albida.

Soil cores were drilled under the leguminous tree Acacia albida growing in two different ecoclimatic zones of West Africa: the Sahelian area (100 to 500 mm of annual rainfall) and the Sudano-Guinean area (1,000 to 1,500 mm of annual rainfall). Soil samples were collected at different depths from the surface down to the water table level and analyzed for the presence of rhizobia able to nodulate A. albida. In both areas, population densities of rhizobia were substantially greater near the water table than near the surface. In the Sahelian area, rhizobia were present as deep as 34 m at a concentration of 1.3 x 10/g of soil. In the Sudano-Guinean area, population densities at 0.5 to 4.5 m depth were higher than in the Sahelian area and, at several depths, comparable to that of temperate soils supporting legume crops (10 rhizobia per g of soil). Surface and deep soil isolates from all four sites were found to be slow-growing rhizobia (Bradyrhizobium sp.). The proportion of effective isolates was almost the same within surface and deep soils.

Journal Article↗

Inoculation of Acacia mangium with Alginate Beads Containing Selected Bradyrhizobium Strains under Field Conditions: Long-Term Effect on Plant Growth and Persistence of the Introduced Strains in Soil.

The growth response of Acacia mangium Willd. to inoculation with selected Bradyrhizobium strains was investigated in two field trials in the Ivory Coast (West Africa). In the first trial (Anguededou), four provenances (i.e., trees originating from seeds harvested in different geographical areas) of A. mangium were inoculated with four Bradyrhizobium strains from different origins. Six months after being transplanted in the field, the heights of all inoculated trees showed a statistically significant increase of 9 to 26% compared with those of uninoculated trees, with the most effective strain being Aust 13c. After 19 months, the positive effect of inoculation on tree growth was confirmed. The effect of A. mangium provenance on tree growth was also highly significant. Trees from the Oriomo provenance of Papua New Guinea had a mean height that was 25% greater than those of other provenances. Analysis of variance showed a highly significant effect of interaction between strain and host provenance factors. Thus, most effective strain x provenance combinations could be proposed. Immunological identification of strains clearly showed that 90 to 100% of nodules from trees inoculated with three of the four Bradyrhizobium strains or from uninoculated trees contained exclusively Aust 13c 23 months after tree transplantation. This predominance of Aust 13c in nodules was still observed 42 months after tree transplantation. The second experiment (Port-Bouët), performed with a different soil, confirmed the long-term positive effect of Aust 13c on plant growth, its high competitive ability against indigenous strains, and its persistence in soil. Strain Aust 13c should thus be of great interest for inoculating A. mangium under a wide range of field conditions.

Journal Article↗

Triterpene glycosides from the bark of Robinia pseudo-acacia L. I.

From the bark of Robinia pseudo-acacia L., five new triterpene glycosides, robiniosides A-D (3, 5-7) and compound III (4), were isolated and their structures were elucidated as 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl(1-->2)-beta-D- glucuronopyranosyl 3 beta,22 beta-dihydroxyolean-12-en-29-oic acid (3), 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D -glucuronopyranosyl 3 beta,22 beta,24-trihydroxyolean-12-en-29-oic acid (4), whose sapogenol was unambiguously characterized and designated as oxytrogenin, 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl(1-->2)-beta-D glucuronopyranosyl oxytrogen (5), 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D galactopyranosyl(1-->2)-beta-D-glucuronopyranosyl oxytrogenin 22-O-alpha-L-rhamnopyranoside (6), 3-O-alpha-L- rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl(1-->2)-beta-D-glucuronop yranosyl oxytrogenin 22-O-alpha-L-rhamnopyranoside (7), respectively, together with two known triterpene glycosides, kaikasaponin III (1) and 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D - glucuronopyranosyl 3 beta,22 beta-dihydroxyolean-12-en-29-oic acid (2).

Carbohydrate Sequence↗

Triterpene glycosides from the bark of Robinia pseudo-acacia L. II.

From the bark of Robinia pseudo-acacia L., six new triterpene glycosides, Robiniosides E--J, were isolated and their structures were elucidated as abrisapogenol B 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D - glucuronopyranoside (1), abrisapogenol B 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D- glucopyranosyl(1-->2)-beta-D-glucuronopyranoside (2), 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D - glucuronopyranosyl abrisapogenol B 22-O-alpha-L-rhamnopyranoside (3), 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D- glucopyranosyl(1-->2)-beta-D-glucuronopyranosyl abrisapogenol B 22-O-alpha-L-rhamnopyranoside (4), 3-O-alpha-L- rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D-glucuron opyranosyl abrisapogenol E 30-O-beta-D-apiofuranosyl(1-->6)-beta-D-glucopyranoside (5) and 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl(1-->2)-beta-D- glucuronopyranosyl abrisapogenol E 30-O-beta-D-apiofuranosyl(1-->6)-beta-D-glucopyranoside (6), respectively.

Carbohydrate Sequence↗

Particle size analysis of gelatin-acacia coacervate and ethylcellulose walled microcapsules.

The Coulter counter has become one of the methods of choice for the measurement of small particle sizes. However, many colloidal walled microcapsules are prone to hydration when dispersed in the electrolyte solution used in Coulter measurements. This hydration causes the walls to swell, producing different size analyses dependent upon the time of measurement. In the present work the change in size with time was studied for microcapsules with gelatin-acacia coacervate, or ethylcellulose, walls. The former, although rendered insoluble with formalin, still hydrated; the latter were almost unaffected by water. A sample size of 30 mg was required to prevent blocking of the orifice with larger samples, or too few particles to permit measurement in smaller samples. The coacervate coated microcapsules showed a bimodal distribution, in part due to aggregate of smaller microcapsules, and this distribution changed significantly over the time of measurement. Although the peak due to larger microcapsules did not disappear, the number of large microcapsules fell significantly, most probably because of the disintegration of aggregated microcapsules. Microcapsules with ethyl cellulose walls did not show a bimodal distribution and the particle size analysis did not alter significantly with time.

Capsules↗