Contribution of Secondary Metabolites to the Gastroprotective Effect of Aqueous Extract of Ximenia americana L. (Olacaceae) Stem Bark in Rats.

Ximenia americana L. (Olacaceae) is used in ethnomedicine as cicatrizant and for the treatment of gastric disorders. This study identified the chemical constituents of the aqueous extract of X. americana (XaAE) and evaluated its antiulcerogenic activity. After lyophilization, XaAE was analyzed by liquid chromatography-mass spectrometry (LC-MS) and its antiulcerogenic effect was evaluated in acute gastric lesions induced by ethanol, acidified ethanol, and indomethacin. Antisecretory action, mucus production and the participation of sulfhydryl groups (-SH) and nitric oxide (NO) were also investigated. The chromatographic analysis identified procyanidins B and C and catechin/epicatechin as major compounds. Oral administration of XaAE (100, 200 and 400 mg/kg) inhibited the gastric lesions induced by ethanol (76.1%, 77.5% and 100%, respectively), acidified ethanol (44.9%, 80.6% and 94.9%, respectively) and indomethacin (56.4%, 52.7% and 64.9%, respectively). XaAE reduced gastric contents and acidity (51.4% and 67.7%, respectively) but did not alter the production of gastric mucus. The reduction of the -SH and NO groups promoted by N-ethylmaleimide (NEM) and Nω-nitro-l-arginine-methyl-ester (L-NAME) respectively, reduced the gastroprotective effect of XaAE. In conclusion, XaAE has gastroprotective activity mediated in part by -SH, NO and antisecretory activity. This antiulcer action was initially correlated to its major constituents, procyanidins B and C and catechin/epicatechin.

Effect of dietary Ximenia caffra kernel meal on blood and liver metabolic substrate content and the general clinical biochemistry of Sprague Dawley rats.

We investigated (at the University of the Witwatersrand: GPS coordinates 26°10' 52.96″S; 28°2' 33.61″E) the effects of substituting soya bean meal (SBM) with Ximenia caffra kernel meal (XCKM) as a dietary protein source on blood and liver metabolic substrates content, serum markers of liver and kidney function and the general clinical biochemistry of Sprague Dawley (SD) rats. Five diets with similar energy and protein content were formulated (D1-D5) where XCKM replaced SBM on a crude protein basis at 0, 25, 50, 75 and 100%. Forty weanling male SD rats were randomly assigned to diets D1-D5, fed for 37 days and weighed twice weekly. The rats were then fasted overnight, and fasting blood glucose and triglyceride concentrations were determined from tail-vein-drawn blood. Immediately thereafter, the rats were euthanised and blood was collected via cardiac puncture. Serum was used to assay for markers of the general health profile. Livers were removed and weighed, and samples were used to determine lipid and glycogen content. Rats fed D4 (75% substitution level) had significantly lower (p < 0.05) blood triglyceride content compared with rats fed D2 (25% level of substitution). The substitution of SBM with XCKM did not affect (p > 0.05) fasting blood glucose and cholesterol concentrations, liver glycogen and lipid content. Additionally, it had no effect (p > 0.05) on serum activity/concentration of surrogate markers of liver (alanine aminotransferase and alkaline phosphatase activity and urea, total bilirubin, globulin and albumin concentrations) and kidney (phosphorus, calcium and creatinine concentrations) function and the general clinical biochemistry of the rats. Defatted XCKM could substitute SBM in rat diets without compromising blood glucose and cholesterol homeostasis, liver and kidney function and the general clinical biochemistry of growing male Sprague Dawley rats.

Antiulcer Effect of Aqueous Ethanolic Extracts of Pseudocedrela kotschyi (Schweinf) Harms (Meliaceae) and Ximenia americana L. (Olacaceae).

Purpose: This study aimed to provide pharmacological evidence of Pseudocedrela kotschyi and Ximenia americana in preventing or healing peptic ulcers claimed by traditional healers in Burkina Faso. Methods: The trunk bark of Pseudocedrela kotschyi and the roots bark of Ximenia americana (Olacaceae) were macerated in mixed ethanol/water (80:20), respectively, to obtain dried extracts. Two models of hydrochloric acid (HCl, 0.3 M/ethanol, 60%) and hypothermic stress-induced peptic ulcer were used. The cytoprotective effect of individual or combined plant extracts was assessed at 1; 10; 30mg/kg. bw. Then, the healing effect of the extracts at 10mg/kg.bw was evaluated within 21 days of treatment on the hydrochloric acid-induced ulcer model. The extracts' antioxidant activity and phenolic content were assessed to support the plant extracts' efficiency. Results: The extracts of P. kotschyi and X. americana at 10 mg/kg.bw reduced ulceration index in hydrochloric acid- and hypothermic stress-ulcer models by more than 83% and 65%, respectively. The extract from X. americana at 10mg/kg.bw allowed complete ulcer healing but not the association of the two plant extracts. The plant extracts had IC50of inhibition of DPPH radical lower than 5µg/mL and total ferric reducing antioxidant power of more than 77 mg EQAA/100mg. The total polyphenolic content was 64.82 ±0.99 and 53.75 ±1.39 mg EGA/g of dried extract of P. kotschyi and X. americana, respectively. Conclusion: X. americana extract is better than the combined two plant extracts in gastric cytoprotection and ulcer healing. Further investigations are needed to highlight mechanism-based effects.

Bioactive composition, free radical scavenging and fatty acid profile of Ximenia americana grown in Ethiopia.

Ximenia americana is among wild edible fruit indigenous to Ethiopia. The fruit reported as indispensable source of phytochemicals and health imparting components. However, the phytochemicals constituents, antioxidant activities and fatty acid profile of Ethiopian X. americana cultivar studies are still scarce. This research aimed at evaluation of flesh and seed of Ethiopian X. americana yellow and red colored cultivars for bioactive component, antioxidant activities, fatty acid profiles and physicochemical characteristics. The red fruit flesh had higher total phenol (3292.60 mg GAE/100 g) while yellow fruit flesh showed higher total flavonoid (173.95 mg quercetin/100g). The higher DPPH∗ radical scavenging activity (97%) was observed in red fruit flesh due to its higher phenolic content. The yellow X. americana seed (90.69 mg QE/100g) had higher total flavonoid contents than the red seed (18.64 mg QE/100g). The dominant unsaturated fatty acid found in red X. americana flesh was oleic acid (26.29%), and the main saturated fatty acid detected was palmitic acid (29.78%). The seed also had high unsaturated fatty acid which was elaidic acid, (84.32%). Ximeninic acid (12.78%) which is expected to be detected in Ximenia americana seed oil was also observed. The highest content of fat (52.23%) and protein (16.59%) was obtained in yellow fruit seed and the lowest fat content observed in yellow flesh (7.25%). Most abundant minerals were calcium (42.45-49.55 mg/100g) and manganese (26.73-33.92 mg/100g) in seeds. Whereas, fleshs displayed higher magnesium (76.3-98.27 mg/100g) and copper (1.35-1.52 mg/100g) contents. The Ethiopian X. americana fruit cultivars represent high nutritional and medicinal values despite variation related to genetic variability.

Phytochemical study, molecular docking, genotoxicity and therapeutic efficacy of the aqueous extract of the stem bark of Ximenia americana L. in the treatment of experimental COPD in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ximenia americana L. is popularly known as yellow plum, brave plum or tallow wood. All the parts of this plant are used in popular medicine. Its reddish and smooth bark are used to treat skin infections, inflammation of the mucous membranes and in the wound healing process. OBJECTIVE: Verification of phytochemical profile, the molecular interaction between flavonoid, (-) epi-catechin and 5-LOX enzyme, by means of in silico study, the genotoxic effect and to investigate the pharmacological action of the aqueous extract of the stem bark of X. americana in pulmonary alterations caused by experimental COPD in Rattus norvegicus. MATERIALS AND METHODS: The identification of secondary metabolites was carried out by TLC and HPLC chromatographic methods, molecular anchoring tests were applied to analyze the interaction of flavonoid present in the extract with the enzyme involved in pulmonary inflammation process and the genotoxic effect was assessed by comet assay and micronucleus test. For induction of COPD, male rats were distributed in seven groups. The control group was exposed only to ambient air and six were subjected to passive smoke inhalations for 20 min/day for 60 days. One of the groups exposed to cigarette smoke did not receive treatment. The others were treated by inhalation with beclomethasone dipropionate (400 mcg/kg) and aqueous and lyophilized extracts of X. americana (500 mg/kg) separately or in combination for a period of 15 days. The structural and inflammatory pulmonary alterations were evaluated by histological examination. Additional morphometric analyses were performed, including the alveolar diameter and the thickness of the right ventricle wall. RESULTS: The results showed that the aqueous extract of the bark of X. americana possesses (-) epi -catechin, in silico studies with 5-LOX indicate that the EpiC ligand showed better affinity parameters than the AracA ligand, which is in accordance with the results obtained in vivo studies. Genotoxity was not observed at the dose tested and the extract was able to stagnate the alveolar enlargement caused by the destruction of the interalveolar septa, attenuation of mucus production and decrease the presence of collagen fibers in the bronchi of animals submitted to cigarette smoke. CONCLUSION: Altogether, the results proved that the aqueous extract of X. americana presents itself as a new option of therapeutic approach in the treatment of COPD.

Ximenia americana L. enhances the antibiotic activity and inhibit the development of kinetoplastid parasites.

OBJECTIVE: The objective of this work was evaluate the cytotoxic, leishmanicidal and tripanocidal activity, as well as to evaluate its antimicrobial and modulatory activity in association with different antibiotics of the hydroethanolic extract of the Ximenia Americana stem bark (EHXA). METHOD: In vitro tests against Trypanosoma cruzi, Leishmania sp. and citotoxicity were performed. The evaluation of the antibacterial and bacterial resistance modulatory effect was given by the microdilution method. RESULTS: The chemical profile show different classes of compounds with significant presence of quercetrin and caffeic acid. The EHXA demonstrated activity only in the concentration of 1000 µg/mL against the L. infantum and L. brasiliensis promastigotes, causing mortality percentage of 40.66 and 27.62%, respectively. The extract presented a significant toxicity only in the concentration of 1000 µg/mL, causing a mortality of 55.42% of fibroblasts. The antibacterial activity of the EHXA demonstrated a MIC value ≥1024 µg/mL against all the tested bacteria. However, in the modulation assay with EHXA in association with different antibiotics the extract had a synergistic effect against S. aureus strains when associated with norfloxacin. CONCLUSION: The results of this investigation demonstrate for the first time the chemical composition of the hydroethanolic extract of the Ximenia Americana stem bark, your potential antiparasitic and modulatory effect. The low cytotoxic and biological potential against S. aureus open therapeutic perspectives against leishmaniosis and bacterial infections.

An Overview on the Properties of Ximenia Oil Used as Cosmetic in Angola.

Ximenia (Ximeniaamericana L.) is a shrub, or small tree, native from Africa and spread across different continents. In Angola, the seeds oil is used by local populations, to prevent sunburn, to smooth and hydrate the skin, and to give it a pleasant color and elasticity, to prevent stretch marks, in pregnant woman, and also as hair conditioner. Herein, an oil sold in the region (LPO), and two others extracted in laboratory, from seeds collected in the same region, were investigated in terms of their composition, chemical properties, UV transmission. The three oils are similar although the LPO is more acidic, 0.48 mg KOH/g. GC-MS analysis indicated that the major components are the fatty acids, oleic (31.82%), nervonic (11.09%), ximenic (10.22%), and hexacosa-17,20,23-trienoic acids (14.59%). Long chain fatty acids, n ≥ 20, accounted for 51.1% of the total fatty acids. A thin film of the oil showed a reduction in transmittance from 200 to 300 nm. Viscosity studies of the LPO indicated that at normal temperature of skin, the oil can be spread over the skin as a thin film. At concentrations up to 10 µg/mL, the LPO is not toxic to human keratinocytes, suggesting the safety of this oil.

Tablet of Ximenia Americana L. Developed from Mucoadhesive Polymers for Future Use in Oral Treatment of Fungal Infections.

The use of biocompatible polymers such as Hydroxypropylmethylcellulose (HPMC), Hydroxyethylcellulose (HEC), Carboxymethylcellulose (CMC), and Carbopol in solid formulations results in mucoadhesive systems capable of promoting the prolonged and localized release of Active Pharmaceutical Ingredients (APIs). This strategy represents a technological innovation that can be applied to improving the treatment of oral infections, such as oral candidiasis. Therefore, the aim of this study was to develop a tablet of Ximenia americana L. from mucoadhesive polymers for use in the treatment of oral candidiasis. An X. americana extract (MIC of 125 µg·mL-1) was obtained by turbolysis at 50% of ethanol, a level that demonstrated activity against Candida albicans. Differential Thermal Analysis and Fourier Transform Infrared Spectroscopy techniques allowed the choice of HPMC as a mucoadhesive agent, besides polyvinylpyrrolidone, magnesium stearate, and mannitol to integrate the formulation of X. americana. These excipients were granulated with an ethanolic solution 70% v/v at PVP 5%, and a mucoadhesive tablet was obtained by compression. Finally, mucoadhesive strength was evaluated, and the results demonstrated good mucoadhesive forces in mucin disk and pig buccal mucosa. Therefore, the study allowed a new alternative to be developed for the treatment of buccal candidiasis, one which overcomes the inconveniences of common treatments, costs little, and facilitates patients' adhesion.

HPLC profile and antiedematogenic activity of Ximenia americana L. (Olacaceae) in mice models of skin inflammation.

The aim of this study was to evaluate the anti-edematogenic activity of X. americana L. (HEXA) hydroethanolic extract in ear edema models (acute and chronic) induced by croton oil and by different phlogistic agents (arachidonic acid, capsaicin, phenol and histamine), identifying the possible anti-edematogenic mechanism. HEXA demonstrated a significant anti-edematogenic effect at concentrations of 100-500 µg/ear in ear edema induced by croton oil with higher inhibition of edema of 39.37. However, the concentrations of 100 and 200 µg/ear were taken as a standard, demonstrating the effect in the chronic model induced by croton oil with inhibition of 61.62% and 48.74%. In the AA-induced ear edema model, HEXA showed inhibition of: 24.45% and 32.31%; capsaicin inhibition of 72.72% and 47.57%; phenol inhibition of 34% and 20.1%; and histamine inhibition of 31.8% and 21.62%. Then, the results were showed that HEXA demonstrated an anti-edematogenic effect in acute and chronic inflammation models, demonstrating a probable mechanism of action by the inhibition or modulation of key mediators of the inflammatory process. The chemical profile and presence of flavonoids guaranteeing a profile of activity similar to natural drugs that act or modulate the production of mediators of inflammations.

The ribosome inhibiting protein riproximin shows antineoplastic activity in experimental pancreatic cancer liver metastasis.

Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses of all malignancy types. To improve the survival of patients with PDAC, the development of novel anticancer agents is warranted. Riproximin (Rpx) is a newly identified plant lectin, which was isolated from Ximenia americana. The ribosome inactivating protein of type II exhibits potent anticancer activity as recently demonstrated. The rat PDAC cell line ASML was used for in vitro and in vivo studies. The antiproliferative effect of Rpx was assessed using an MTT assay. The modulation of proteins involved in apoptosis was evaluated using western blotting. Tumor-bearing nude rats were treated with Rpx, gemcitabine (GEM) or dinaline (DIN) as single agents, or a combination of Rpx with GEM, or DIN. Rpx was administered intraperitoneally at doses of 1.7-5.4 µg/kg, three times/week, GEM was administered intravenously (50 mg/kg/week) and DIN perorally (10 mg/kg, 5 times/week). Rpx inhibited ASML cell proliferation at IC50-values of 0.8-172 pM, caused apoptosis and reduced tumor growth significantly by 90% (P<0.05). The survival rate of rats was significantly increased (21.8 days for Rpx treated vs. 17.6 days for control rats; P=0.05). Higher doses of Rpx caused no further reduction in tumor size when compared with the low dose of Rpx or a combination of Rpx with GEM, or DIN. The standard drug GEM alone was less effective compared with Rpx. In addition, DIN was ineffective, and in combination, reduced the activity of Rpx. These results suggest that Rpx has an evident potential for use in pancreatic cancer treatment. Further experiments are required in order to elucidate its affinity for certain cancer cells and to optimize the combination therapy with other antineoplastic agents.

Effects of Dietary Ximenia caffra Meal on Nutrient Intake, Digestibility, Nitrogen Balance and Growth Performance in Sprague Dawley Rats Modelling Monogastrics.

BACKGROUND AND OBJECTIVE: The sub-saharan livestock feed industry depends on imported soyabean meal (SBM) as a dietary protein source in feeds thus making livestock production costly. This calls for the search and development of local dietary protein sources. Using Sprague Dawley rats to model monogastric animals, this study evaluated the potential of Ximenia caffra kernel meal (XCKM) to substitute SBM as a dietary protein source in feeds. MATERIALS AND METHODS: Five diets were formulated wherein XCKM replaced SBM on a crude protein basis at 0, 25, 50, 75 and 100%. In the digestibility trial, 20 adult male SD rats were randomly assigned to the 5 diets. After a 12-day adaptation period feed and nutrient intake, faeces and urine output were determined over a 5-day collection period. Apparent Total Tract Digestibility (ATTD) of nutrients and nitrogen absorption and retention were determined. In the growth trial, 40 weanling male SD rats were randomly assigned to the five dietary treatments and fed for 38 days. The rats were weighed twice weekly. Following euthanasia, gastrointestinal viscera were harvested and their macro-morphometry determined. Linear growth was determined from tibiae and femora indices. RESULTS: In adult rats dietary XCKM had no (p>0.05) effect on ATTD of nutrients. At 100% substitution of SBM, XCKM increased (p<0.05) faecal nitrogen loss while at 75% substitution level it increased (p<0.05) nitrogen retention. In growing SD rats, although dietary XCKM had no effect (p>0.05) on the terminal body and empty carcass mass and viscera macro-morphometry, at 100% SBM substitution, it significantly compromised (p<0.05) body mass gain and average daily gain. Femora and tibiae mass and seed or index significantly decreased (p<0.05) with increased dietary XCKM. CONCLUSION: The XCKM could replace SBM as a dietary protein source in adult SD rat feeds without compromising ATTD digestibility of nutrients and nitrogen utilization thus it could be speculated that XCKM can be utilized as a dietary protein source in feeds of mature monogastrics. Caution must be exercised in using XCKM in grower rat diets as its use at higher inclusion levels compromised growth performance and long bone health.

Hepatoprotective and hypoglycemic effects of a tannin rich extract from Ximenia americana var. caffra root.

BACKGROUND: Liver diseases and diabetes are serious health disorders associated with oxidative stress and ageing. Some plant polyphenols can lower the risk of these diseases. PURPOSE: We investigated the phytochemical profiling of a root extract from Ximenia americana var. caffra using HPLC-PDA-ESI-MS/MS. The antioxidant activities in vitro were investigated. The hepatoprotective activities were studied in rat models with d-galactosamine (d-GaIN)-induced hepatotoxicity and the antidiabetic activities in STZ-diabetic rats were also investigated. MATERIALS AND METHODS: HPLC-PDA-ESI-MS/MS was used to identify plant phenolics. The antioxidant activities in vitro were determined using DPPH and FRAP assays. The in vivo hepatoprotective activities were determined for d-GaIN-induced hepatotoxicity in rats. We determined the liver markers alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), liver peroxidation product malondialdehyde (MDA), glutathione content (GSH), albumin and total bilirubin concentration. The histopathological changes in rat liver were also studied. The antidiabetic activities were also investigated in STZ-diabetic rats and serum glucose, serum insulin hormone, and lipid peroxides were determined. RESULTS: The root extract is rich in tannins with 20 compounds including a series of stereoisomers of (epi)catechin, (epi)catechin-(epi)catechin, (epi)catechin-(epi)catechin-(epi)catechin, and their galloyl esters. Promising antioxidant potential was observed in vitro in DPPH assay with EC50 of 6.5 µg extract / 26 µg raw material and in FRAP assay with 19.54 mM FeSO4 compared with ascorbic acid (EC50 of 2.92 µg/ml) and quercetin (FeSO4 24.04 mM/mg), respectively. Significant reduction of serologic enzymatic markers and hepatic oxidative stress markers such as ALT, AST, MDA, GGT, and total bilirubin, as well as elevation of GSH and albumin were observed in rats with d-galactosamine-induced liver damage treated with the extract. These findings agree with a histopathological examination suggesting a hepatoprotective potential for the root extract. The root extract can mediate an antidiabetic effect by reducing elevated blood glucose and serum lipid peroxides levels and by increasing insulin in STZ-diabetic rats by -107, -31.1, +11.3%, respectively. CONCLUSIONS: The results of this study suggest that the tannin-rich extract from Ximenia americana var. caffra could be an interesting candidate for the treatment of several health disorders associated with oxidative stress such as hepatocellular injury and diabetes.

Ximenia caffra Sond. (Ximeniaceae) in sub-Saharan Africa: A synthesis and review of its medicinal potential.

ETHNOPHARMACOLOGICAL RELEVANCE: Ximenia caffra Sond. (Ximeniaceae), commonly known as "sour plum" is traditionally used, both topically and orally to treat a wide range of human diseases and ailments such as wounds, sexually transmitted infections (STIs), infertility, stomach ache, fever, eye problems, diarrhoea, bilharzia, menorrhagia, malaria, intestinal worms, impotence and coughs. The bark and fruits are used by small-scale farmers as ethnoveterinary medicine to treat dermatophilosis, foot rot, saddle sores and control ectoparasites. Oil from X. caffra seed is traditionally used as a moisturiser, soap and shampoo for dry, fragile and damaged hair. AIM OF THE REVIEW: The aim of this study was to comprehensively summarize the research that has been done on the botany, ethnomedicinal uses, phytochemistry and biological activities of X. caffra in different locations throughout its geographical range in the sub-Saharan African region so as to understand its importance and potential in primary healthcare systems. MATERIALS AND METHODS: This study was carried out using a comprehensive and systematic literature search on the ethnomedicinal uses, phytochemistry and biological activities of the species throughout its distributional range. Literature sources included papers published in international journals, reports from international, regional and national organizations, conference papers, books and theses. PubMed and Scopus, search engines such as Google Scholar and online collection ScienceDirect were used. RESULTS: This study showed that X. caffra is used as traditional medicine in 83.3% of the countries in tropical Africa where it is indigenous. A total of 65 human and animal ailments and diseases are recorded for X. caffra, with a high degree of consensus for wounds, sexually transmitted infections (STIs), infertility, stomach ache, fever, eye problems, diarrhoea, bilharzia, menorrhagia, malaria, intestinal worms and coughs. Phytochemical investigation of X. caffra revealed that the species has various compounds including flavonoids, phenols, phytosterols, tannins and fatty acids. Different plant parts, aqueous and organic extracts exhibited anti-amoebic, antibacterial, antifungal, anti-inflammatory, antioxidant, antiparasitic, antiproliferative, HIV-1 reverse transcriptase (RT) inhibitory, insecticidal, non-mutagenic and toxicity activities. CONCLUSION: In this review, the ethnomedicinal uses, phytochemistry, biological activities and toxicity of different extracts and compounds of X. caffra have been summarized. Although many of the ethnomedicinal uses of X. caffra have been validated by phytochemical and pharmacological studies, there are still some gaps where current knowledge could be improved. There are very few to nil experimental animal studies, randomized clinical trials and target-organ toxicity studies involving X. caffra and its derivatives that have been carried out so far. At the present moment, there is not sufficient evidence to interpret the specific chemical mechanisms associated with some of the documented biological activities of the species. Therefore, future studies should identify the bioactive components, details of the molecular modes or mechanisms of action, pharmacokinetics and physiological pathways for specific bioactives of X. caffra.

Bioactive compounds and antioxidant potential fruit of Ximenia americana L.

The caatinga ecoregion in northeast Brazil presents a wide variety in plant species. However, the potential of these species as a source of energy, carbohydrates, vitamins, minerals and bioactive properties beneficial to health is still unknown. Among these species we can find the wild plum (Ximenia americana). Due to its various phytotherapeutic properties and absence of studies on the chemical composition of the fruit this article aimed to evaluate the bioactive compounds and antioxidant potential of the X. americana in different stages of maturation. The fruits of X. americana showed considerable amounts of bioactive compounds, as well as antioxidant activity and antioxidant enzymes. The fruits at green maturity stage showed higher content of yellow flavonoids (22.07 mg/100g), anthocyanins (1.92 mg/100 g), polyphenols (3051.62 mg/100 g), starch (4.22%), antioxidant activity (489.40 g fruit/g DPPH and 198.77 µmol Trolox/g) and activity of antioxidant enzymes; the antioxidant activity allocated to the fruit was shown to be related to the contents of extractable polyphenols, yellow flavonoids, total anthocyanins and antioxidant enzymes.

Riproximin is a recently discovered type II ribosome inactivating protein with potential for treating cancer.

The development of new anticancer drugs is a salient problem and the traditional use of plants is a potentially rich source of information for detecting new molecules with antineoplastic activity. Riproximin is a recently detected cytotoxic type II ribosome inactivating protein with high selectivity for certain tumor cell lines. Its activity was recognized as the main component in a plant powder used by African healers for treating cancer. By ribulose bisphosphate carboxylase gene sequencing analysis, the powder was identified to be derived from the plant Ximenia americana. The cDNA sequence of riproximin was identified, the protein was modeled to contain one A- and a B-chain, respectively, and a reliable purification procedure from kernels of X. americana was established. Riproximin displays high but differential antiproliferative activity in a panel of human and rodent cancer cell lines, with concentrations inhibiting cell proliferation by 50% (IC50 values) that diverge by a factor of 100. Consistent antineoplastic activity was detected in colorectal and pancreatic cancer liver metastasis models in rats. The cytotoxic mechanism of action was determined to be based on cellular uptake of riproximin followed by its A-chain prompted depurination of the 28S ribosomal RNA and induction of unfolded protein response. Riproximin's specificity depended on its B-chain connected binding to cell surface glycans, the presence of which is crucial for subsequent internalization into cells and cytotoxicity. These N- and O-glycans include bi- and tri-antennary NA structures (NA2/NA3) as well as Tn3 structures (clustered Tn antigen). Riproximin was found to crosslink proteins with N- and O-glycan structure, thus indicating both types of binding sites on its B chain. Due to this crosslinking ability, riproximin is expected to show prominent cytotoxicity towards cells expressing both, NA2/NA3 and clustered Tn structures. Apart from the properties of riproximin, the plant X. americana has been known for some medical uses in traditional African medicine, including various types of infections.

Modulation of the erythromycin resistance in Staphylococcus aureus by ethanolic extracts of Ximenia americana L and Schinopsis brasiliensis Engl / Modulación de la resistencia a la eritromicina en Staphylococcus aureus por extractos etanólicos de Ximeniaamericana L y Schinopsis brasiliensis Engl

It was evaluated the in vitro efficacy of ethanolic extract of leaves and bark of Ximenia americana L and Schinopsis brasiliensis Engl. alone and in association with erythromycin as modulators of microbial resistance against six clinical isolates of Staphylococcus aureus resistant to erythromycin (SA1-SA6) and S. aureus ATCC 25923 by the microdilution method. The extracts were also subjected to bioassay with Artemia salina. The ethanolic extract of barks of X. americana showed a synergistic effect with erythromycin against SA01, SA03 and SA04. The leaf extract of S. brasiliensis exerted synergistic effect against SA03 and the bark extract showed against SA01 and S03. The results suggest that extracts from S.brasiliensis and X. americana have potential as modulator agents of bacterial resistance, which could be used as adjuvants in the treatment of infections by S. aureus resistant to erythromycin, with previous studies of toxicity.

Se evaluó la eficacia in vitro de los extractos etanólicos de hojas y corteza de Ximenia americana L y Schinopsis brasiliensis Engl solos y en asociación con eritromicina como moduladores de la resistencia microbiana frente a seis aislados clínicos de Staphylococcus aureus resistentes a Eritromicina (SA1-SA6) y S. aureus ATCC 25923, por el método de microdilución. Además se determinó la actividad tóxica de los extractos contra Artemia salina. Solo el extracto etanólico de la corteza de X. americana mostró un efecto sinérgico con la eritromicina frente a SA01, SA03 y SA04. El extracto de las hojas de S. brasiliensis ejerció efecto sinérgico contra SA03 y el extracto de corteza, contra SA01 y S03. Los resultados sugieren que S. brasiliensis y X. americana tienen potencial como agentes moduladores de la resistencia bacteriana, que podrían ser utilizados como adyuvantes en el tratamiento de infecciones por S. aureus resistentes a eritromicina, con estudios previos de toxicidad.