RESUMEN

BACKGROUND: Although there has developed an increased interest in the vaccines BNT1622b2 (Pfizer/BioNTech), mRNA-1273 (Moderna/NIAID), and ChAdOx1 nCoV-19 (AstraZeneca/University of Oxford), there are still few reports describing the immune response induced by different vaccine platforms in real-world settings of low-income countries. Here, we proposed to analyse the humoral immune response elicited by the primary vaccines used in Argentina from July-December 2021. METHODS: Anti-SARS-CoV-2-Spike-RBD IgG and neutralising antibodies were assayed by ELISA in a total of 871 serum samples obtained from 376 volunteers from an educational staff. The individuals were vaccinated with BBIBP-CorV (Sinopharm), ChAdOx1 nCoV-19 (AstraZeneca/University of Oxford, AZ), Gam-COVID-Vac (Sputnik V, SpV) or combined vaccines (mostly SpV and mRNA-1273, Moderna). The antibody response was analysed several days after the initial vaccination (20, 40, 120 and 180 days). RESULTS: After receiving at least one dose of the COVID-19 vaccine, we detected 93.34% of seroprevalence. Previously SARS-CoV-2 infected showed higher antibody concentrations compared with naïve vaccinees. Six months after the initial vaccination, combined vaccination induced higher anti-SARS-CoV-2 antibody levels than the other vaccines in naïve volunteers. However, we did not find differences in the neutralising responses after any vaccine from naïve vaccines or between the naïve and previously infected volunteers on day 120 after vaccination. CONCLUSIONS: Our long-term analysis of volunteers from the educational system provides data in a real-world context, showing the benefits of a boost dose still in previously infected volunteers, and suggesting the advantages of a heterologous prime-boost schedule.

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , Humanos , ChAdOx1 nCoV-19 , Formación de Anticuerpos , Vacuna nCoV-2019 mRNA-1273 , Argentina , Estudios Seroepidemiológicos , COVID-19/prevención & control , SARS-CoV-2 , Vacunación , Anticuerpos Antivirales , Inmunoglobulina G

RESUMEN

Nitric oxide (NO), a signaling molecule, regulates multiple biological functions, including a variety of physiological and pathological processes. In this regard, NO participates in cutaneous inflammations, modulation of mitochondrial functions, vascular diseases, COVID-19, neurologic diseases, and obesity. It also mediates changes in the skeletal muscle function. Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by the malfunction of phagocytes caused by mutations in some of the genes encoding subunits of the superoxide-generating phagocyte NADPH (NOX). The literature consulted shows that there is a relationship between the production of NO and the NADPH oxidase system, which regulates the persistence of NO in the medium. Nevertheless, the underlying mechanisms of the effects of NO on CGD remain unknown. In this paper, we briefly review the regulatory role of NO in CGD and its potential underlying mechanisms.

RESUMEN

Yersinia enterocolitica (Ye) inserts outer proteins (Yops) into cytoplasm to infect host cells. However, in spite of considerable progress, the mechanisms implicated in this process, including the association of Yops with host proteins, remain unclear. Here, we evaluated the functional role of Galectin-1 (Gal1), an endogenous ß-galactoside-binding protein, in modulating Yop interactions with host cells. Our results showed that Gal1 binds to Yops in a carbohydrate-dependent manner. Interestingly, Gal1 binding to Yops protects these virulence factors from trypsin digestion. Given that early control of Ye infection involves activation of macrophages, we evaluated the role of Gal1 and YopP in the modulation of macrophage function. Although Gal1 and YopP did not influence production of superoxide anion and/or TNF by Ye-infected macrophages, they coordinately inhibited nitric oxide (NO) production. Notably, recombinant Gal1 (rGal1) did not rescue NO increase observed in Lgals1-/- macrophages infected with the YopP mutant Ye ∆yopP. Whereas NO induced apoptosis in macrophages, no significant differences in cell death were detected between Gal1-deficient macrophages infected with Ye ∆yopP, and WT macrophages infected with Ye wt. Strikingly, increased NO production was found in WT macrophages treated with MAPK inhibitors and infected with Ye wt. Finally, rGal1 administration did not reverse the protective effect in Peyer Patches (PPs) of Lgals1-/- mice infected with Ye ∆yopP. Our study reveals a cooperative role of YopP and endogenous Gal1 during Ye infection.

Asunto(s)

Proteínas de la Membrana Bacteriana Externa/metabolismo , Galectina 1/metabolismo , Inmunidad , Óxido Nítrico/biosíntesis , Yersinia enterocolitica/inmunología , Secuencia de Aminoácidos , Animales , Proteínas de la Membrana Bacteriana Externa/química , Ratones Endogámicos C57BL , Ratones Noqueados , Péptido Hidrolasas/metabolismo , Unión Proteica , Proteolisis , Proteómica , Factores de Virulencia/metabolismo , Yersinia enterocolitica/patogenicidad

RESUMEN

Yersinia enterocolitica is an enteropathogenic bacterium that causes gastrointestinal disorders, as well as extraintestinal manifestations. To subvert the host's immune response, Y. enterocolitica uses a type III secretion system consisting of an injectisome and effector proteins, called Yersinia outer proteins (Yops), that modulate activation, signaling, and survival of immune cells. In this article, we show that galectin-1 (Gal-1), an immunoregulatory lectin widely expressed in mucosal tissues, contributes to Y. enterocolitica pathogenicity by undermining protective antibacterial responses. We found higher expression of Gal-1 in the spleen and Peyer's patches of mice infected orogastrically with Y. enterocolitica serotype O:8 compared with noninfected hosts. This effect was prevented when mice were infected with Y. enterocolitica lacking YopP or YopH, two critical effectors involved in bacterial immune evasion. Consistent with a regulatory role for this lectin during Y. enterocolitica pathogenesis, mice lacking Gal-1 showed increased weight and survival, lower bacterial load, and attenuated intestinal pathology compared with wild-type mice. These protective effects involved modulation of NF-κB activation, TNF production, and NO synthesis in mucosal tissue and macrophages, as well as systemic dysregulation of IL-17 and IFN-γ responses. In vivo neutralization of these proinflammatory cytokines impaired bacterial clearance and eliminated host protection conferred by Gal-1 deficiency. Finally, supplementation of recombinant Gal-1 in mice lacking Gal-1 or treatment of wild-type mice with a neutralizing anti-Gal-1 mAb confirmed the immune inhibitory role of this endogenous lectin during Y. enterocolitica infection. Thus, targeting Gal-1-glycan interactions may contribute to reinforce antibacterial responses by reprogramming innate and adaptive immune mechanisms.

Asunto(s)

Galectina 1/metabolismo , Interacciones Huésped-Patógeno , Yersiniosis/inmunología , Yersinia enterocolitica/inmunología , Animales , Carga Bacteriana , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas/genética , Galectina 1/antagonistas & inhibidores , Galectina 1/genética , Galectina 1/inmunología , Interferón gamma/sangre , Interferón gamma/inmunología , Interleucina-17/sangre , Interleucina-17/inmunología , Intestinos/inmunología , Intestinos/microbiología , Intestinos/patología , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/biosíntesis , Ganglios Linfáticos Agregados/inmunología , Ganglios Linfáticos Agregados/microbiología , Ganglios Linfáticos Agregados/patología , Proteínas Tirosina Fosfatasas/deficiencia , Proteínas Tirosina Fosfatasas/genética , Bazo/inmunología , Bazo/microbiología , Factor de Necrosis Tumoral alfa/biosíntesis

RESUMEN

Larrea divaricata Cav. is a plant growing in South America. Both the infusion and a derived fraction (F1) of L. divaricata have proved to have immunomodulatory properties. Moreover, F1 can activate macrophages obtained from mice infected with Candida albicans. In this work, F1 was administrated to infected animals, and the state and type of activation of resident macrophages were studied. Results showed that F1 was able to activate macrophages obtained from infected mice by both classical and alternative pathways, probably by inducing a translocation of nuclear factor kappa-B. F1 increases not only the lysosomal activity of macrophages but also the production of phagosomal superoxide anion as a consequence of the activation of the Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) complex. F1 induced an increase in the macrophage capacity to kill the fungus, which was reflected in a decrease in the levels of colonization of organs. A main flavonoid, kaempferol-3,4'-dimethylether, was identified in F1 by HPLC. This compound increased in vitro production of nitric oxide in heat-killed C. albicans-stimulated macrophages. The flavonoid could thus be considered one of the responsible molecules mediating the overall effects of F1 on the immune system in infected animals.

Asunto(s)

Candida albicans/efectos de los fármacos , Quempferoles/farmacología , Larrea/química , Activación de Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Extractos Vegetales/farmacología , Animales , Candidiasis/inmunología , Femenino , Macrófagos/efectos de los fármacos , Ratones , Extractos Vegetales/química , Hojas de la Planta/química

RESUMEN

Larrea divaricata Cav. (jarilla) is a plant with well-documented applications in Argentinean folk medicine. In order to determine if the treatment with a purified fraction named F1 was capable to maintain a state of priming of macrophages after 15 days of mice infection with Candida albicans. Infected and uninfected mice were used. The effect of F1 on: cytosolic protein levels, apoptosis, phagocytosis, reactive oxygen species production, nitric oxide (NO), cell activity, lysosomal activity and the tissue fungal burden were studied. The results showed that F1 increased macrophages yeast phagocytosis and reactive oxygen species and NO production. All these effects were related to a decrease of cell activity and possible apoptosis. In conclusion, it was observed that F1 could induce a state of long-term activation of macrophages, since we observed increased activity of macrophages 15 days after infection, and it could be related to the elimination of C. albicans. These data may suggest that F1 fraction could be useful against disseminated candidiasis in patients and further studies on this field are desirable.

Asunto(s)

Candida albicans , Candidiasis/tratamiento farmacológico , Larrea/química , Macrófagos Peritoneales/metabolismo , Extractos Vegetales/farmacología , Animales , Apoptosis/efectos de los fármacos , Candidiasis/metabolismo , Candidiasis/patología , Células Cultivadas , Femenino , Macrófagos Peritoneales/microbiología , Macrófagos Peritoneales/patología , Ratones , Óxido Nítrico/biosíntesis , Fagocitosis/efectos de los fármacos , Extractos Vegetales/química , Factores de Tiempo

RESUMEN

AIMS: The macrophage secretions' effect on ovarian steroidogenesis is investigated in a polycystic ovary syndrome rat model (PCO rat). The influence of testosterone environment on the expression of macrophage pro-inflammatory cytokines that participate in ovarian steroidogenesis is studied. MAIN METHODS: PCO rats were induced by estradiol valerate. Spleen macrophages were cultured with and without testosterone (10(-6) M) and their secretions were used to stimulate ovaries from PCO and control rats. Ovarian hormones released and ovary mRNA levels of P450 aromatase and 3ß-hydroxysteroid dehydrogenase were measured by radioimmunoassay and RT-PCR, respectively. The tumor necrosis factor alpha (TNFα) and nitric oxide (NO) levels in macrophage culture medium, along with the TNFα, interleukin (IL)-6, IL-10 and androgen receptors (AR) mRNA levels in macrophage cells were determined. KEY FINDINGS: Macrophages from PCO rats released more TNFα and NO, expressed higher TNFα and IL-6, lower AR, and no change in IL-10 mRNA levels than control macrophages. TNFα, IL-6 and AR changes were greater after macrophage testosterone treatment. Macrophage secretions from PCO rats stimulated androstenedione and decreased estradiol release and ovarian mRNA P450 aromatase expression in PCO rats compared to macrophage secretions from control rats. These effects were greater when macrophages from PCO rats were treated with testosterone. Ovarian progesterone response was unchanged. SIGNIFICANCE: The differential steroidogenic ability of macrophage secretions from PCO rats is associated to the in vitro testosterone environment. Testosterone, probably acting on macrophage AR, induces a greater release of TNFα, modifying ovarian response by increasing androstenedione and slightly decreasing estradiol without affecting progesterone.

Asunto(s)

Citocinas/biosíntesis , Macrófagos/metabolismo , Enfermedades Renales Poliquísticas/metabolismo , Esteroides/biosíntesis , Testosterona/farmacología , Androstenodiona/metabolismo , Animales , Células Cultivadas , Estradiol/análogos & derivados , Estradiol/farmacología , Femenino , Interleucinas/biosíntesis , Macrófagos/efectos de los fármacos , Nitritos/metabolismo , Progesterona/metabolismo , ARN/biosíntesis , ARN/aislamiento & purificación , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Androgénicos/biosíntesis , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Larrea divaricata Cav. (Jarilla) is a bush widely used in folk therapy for the treatment of several pathologies. Partially purified proteins of crude extract (JPCE) cross-react with proteins of Gram-negative bacteria, including Pseudomonas aeruginosa, which is an opportunistic pathogen that causes several intrahospitalary infections. This bacterium produces many proteins with enzymatic activity, including hemolysins and proteases that play a major role in acute infection caused by this bacterium. The aim of our work was to investigate if antibodies against with L. divaricata neutralize the hemolytic and proteolytic activity of P. aeruginosa. The hemolytic activity of soluble cellular proteins was inhibited 100% and extracellular proteins (EP) showed an inhibition between 44 and 95% when both bacterial fractions were treated with anti-JPCE serum. Also, in EP the neutralization was directed towards the active site of the hemolysin. When protease activity of extracellular products was tested, bands of 217, 155, 121, 47 and 27 kDa were observed in native zymograms. Neutralization between 55 and 70% of the bands of 217, 155 and 121 kDa was observed when EP were treated with anti-JPCE serum. In conclusion, our data clearly demonstrate that antibodies elicited with L. divaricata' proteins are able to neutralize the hemolytic and proteolytic activity of P. aeruginosa cellular and extracellular proteins. Our study constitutes the first report that associates the immunogenicity of plant proteins and bacterial proteins with enzymatic activity. These findings could be relevant in the development of alternatives therapies for patients suffering intrahospitalary opportunistic infections with P. aeruginosa.

Asunto(s)

Anticuerpos Neutralizantes/farmacología , Biocatálisis/efectos de los fármacos , Reacciones Cruzadas/inmunología , Enzimas/inmunología , Larrea/enzimología , Proteínas de Plantas/inmunología , Pseudomonas aeruginosa/enzimología , Animales , Anticuerpos Neutralizantes/inmunología , Antígenos de Plantas/inmunología , Antígenos de Plantas/aislamiento & purificación , Antígenos de Plantas/metabolismo , Antígenos de Plantas/farmacología , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/aislamiento & purificación , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/farmacología , Extractos Celulares/química , Medios de Cultivo Condicionados/química , Enzimas/metabolismo , Femenino , Hemólisis/efectos de los fármacos , Humanos , Sueros Inmunes/inmunología , Sueros Inmunes/farmacología , Larrea/química , Masculino , Mercaptoetanol/farmacología , Ratones , Ratones Endogámicos , Péptido Hidrolasas/inmunología , Péptido Hidrolasas/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Hojas de la Planta/enzimología , Proteínas de Plantas/aislamiento & purificación , Proteínas de Plantas/metabolismo , Proteínas de Plantas/farmacología , Tallos de la Planta/química , Tallos de la Planta/enzimología , Inhibidores de Proteasas/inmunología , Inhibidores de Proteasas/farmacología , Desnaturalización Proteica/efectos de los fármacos , Pseudomonas aeruginosa/química , Vacunación/métodos

RESUMEN

Larrea divaricata Cav. is widely distributed in Argentina. Aqueous extract, of its leaves, has documented antitumoral and immunomodulatory activities. In this study, the antioxidant activity of aqueous extract and a component, nordihydroguaiaretic acid was determined and compared using different assays. Both the aqueous extract and nordihydroguaiaretic acid exhibited antioxidant activity. However, results show that it is very likely that compounds other than nordihydroguaiaretic acid could be involved in the antioxidant activity of the extract. Since nordihydroguaiaretic acid is nephrotoxic and hepatotoxic agent, it is important to direct efforts toward the potential use of low-nordihydroguaiaretic acid L. divaricata extracts as antioxidant in foods.

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Larrea divaricata Cav. está ampliamente distribuida en la Argentina. Se han documentado actividades antitumorales e inmunomoduladoras de los extractos acuosos de sus hojas. En este estudio, la actividad antioxidante del extracto acuoso y un componente, el ácido nordihidroguayarético, se determinaron y compararon mediante diferentes ensayos. Tanto el extracto acuoso como el ácido nordihidroguayarético mostraron actividad antioxidante. Sin embargo, los resultados muestran que es muy probable que otros compuestos diferentes al ácido nordihidroguayarético pudieran estar involucrados en la actividad antioxidante de los extractos. Dado que el ácido nordihidroguayarético es un agente nefrotóxico y hepatotóxico, es importante dirigir los esfuerzos hacia el uso potencial de extractos de L. divaricata con bajas cantidades de ácido nordihidroguayarético como antioxidantes en alimentos.

Asunto(s)

Antioxidantes , Catalasa , Larrea , Masoprocol , Superóxido Dismutasa

RESUMEN

Innate immune cells have evolved to sense microbial pathogens through pattern recognition receptors (PRRs), which interact with conserved pathogen-associated molecular patterns (PAMPs) to convey microbial information into immune cell signaling and activation events. PRRs also recognize endogenous damage-associated molecular patterns (DAMPs), including alarmins released during microbial invasion, initiation of autoimmune inflammation or tumor growth. In spite of the well-established role of Toll-like receptors (TLRs) in mediating these recognition events, compelling evidence supports a central function for lectin-glycan interactions in promoting microbial sensing and evoking immune responses. Here we discuss the role of glycans and lectins (particularly galectins) in mediating microbial recognition and initiation of innate immune responses. Both microbes and host cells are sources of glycan-containing information which is, at least in part, decoded by endogenous glycan-binding proteins or lectins, including C-type lectins, siglecs and galectins. Although C-type lectins and siglecs can recognize microbial glycans when expressed on the cell surface of innate immune cells, galectins mainly function as soluble mediators that bridge microbial or host glycans to amplify or attenuate immune responses. Galectins are widely expressed in host cells and play important roles during different steps of infection such as pathogen recognition, invasion and resolution. In addition, recent studies report the presence of conserved 'galectin-like' domains in certain pathogens including helminths and protistan parasites, suggesting that they could also serve as potential virulence factors that influence the outcome and course of infection. Understanding the role of lectin-glycan interactions and the relevance of PRR or PAMP glycosylation in microbial recognition might contribute to the design of novel prophylactic and therapeutic strategies.

Asunto(s)

Antígenos Helmínticos/inmunología , Galectinas/inmunología , Infecciones/inmunología , Polisacáridos/inmunología , Receptores Toll-Like/inmunología , Animales , Galectinas/metabolismo , Glicosilación , Helmintos/inmunología , Humanos , Inmunidad Innata , Infecciones/tratamiento farmacológico , Ligandos , Terapia Molecular Dirigida , Polisacáridos/metabolismo , Unión Proteica , Homología Estructural de Proteína , Receptores Toll-Like/agonistas

RESUMEN

Larrea divaricata Cav. (jarilla) is a plant with well-documented applications in folk medicine in Argentina. In this study, we aimed to evaluate functional parameters of peritoneal macrophages isolated from mice injected with three fractions (F1, F2 and F3) of L. divaricata. The response of macrophages against Candida albicans was evaluated. Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, apoptosis was evaluated using Giemsa, acridine orange/ethidium bromide and ladder assay, oxidative burst was assayed using nitroblue tetrazolium test and nitrite production using Griess assay. Cell stimulation and their ability to kill C. albicans in vitro were measured. The number and cell viability were similar to controls. However, we found that F1 induces pre-activation of macrophages, and this pre-activation is enhanced by C. albicans. The effects exerted by F1 make it more important than F2 and F3 for the treatment of disseminated candidiasis in patients with immunodeficiency diseases such as AIDS and chronic granulomatous disease, among others.

Asunto(s)

Candida albicans/inmunología , Factores Inmunológicos/farmacología , Larrea/química , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Extractos Vegetales/farmacología , Animales , Apoptosis , Supervivencia Celular , Células Cultivadas , Fragmentación del ADN , Etidio/metabolismo , Femenino , Factores Inmunológicos/aislamiento & purificación , Masculino , Ratones , Nitritos/metabolismo , Nitroazul de Tetrazolio/metabolismo , Extractos Vegetales/aislamiento & purificación , Estallido Respiratorio , Coloración y Etiquetado/métodos , Sales de Tetrazolio/metabolismo , Tiazoles/metabolismo

RESUMEN

Vicenin-2 (1), a flavonoid glycoside, was isolated and identified from an ethanol extract of the aerial parts of Urtica circularis. This crude extract was found to possess significant anti-inflammatory activity in a carrageenan-induced rat hind paw edema model (41.5% inhibition at a dose of 300 mg/kg; ip). The effects of 1 on several inflammatory mediators were investigated. In cultured murine macrophages, this compound modified LPS-induced total nitrite and TNF-α production, in addition to the LPS-induced translocation of the nuclear factor NF-κB.

Asunto(s)

Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Apigenina/aislamiento & purificación , Apigenina/farmacología , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Urticaceae/química , Animales , Antiinflamatorios/química , Apigenina/química , Edema/inducido químicamente , Edema/tratamiento farmacológico , Glucósidos/química , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , FN-kappa B/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Nitritos/farmacología , Ratas , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores

RESUMEN

The salivary glands are important exocrine and endocrine organs, whose role in oral health is well recognized. Also these glands contribute to the maintenance of systemic health. During diabetes an impairment of salivary glands is reported. In this work the oxidative stress produced after 10days of a single dose of streptozotocin administration in rats was observed in submandibulary glands. Under this condition a misbalance of the enzymes with antioxidant activity was observed in glands and in incubation medium, as well as in reactive oxygen species such as hydrogen peroxide (H(2)O(2)), superoxide anion (O(2)(-)) and nitric oxide (NO). An increase of NO and H(2)O(2) and a decrease of O(2)(-) were found. A direct relationship between peroxidase and nitric oxide synthase (iNOS) activities with enzyme expression was recorded, in contrast an inverse relationship between superoxide dismutase activity and expression was observed. If the high level of H(2)O(2) persists in time as well as a low level of peroxidase, oral pathologies are expected to occur. So, under this situation to study the modulation of enzymes involved in reactive oxygen species metabolism during oxidative stress in oral tissues could be very important in the managing of oral pathologies.

Asunto(s)

Antioxidantes/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Estreptozocina/farmacología , Glándula Submandibular/efectos de los fármacos , Glándula Submandibular/metabolismo , Animales , Activación Enzimática/efectos de los fármacos , Femenino , Oxidación-Reducción/efectos de los fármacos , Oxidorreductasas/metabolismo , Ratas , Ratas Wistar , Glándula Submandibular/enzimología

RESUMEN

Larrea divaricata Cav. (jarilla) (Zygophyllaceae) is used in Argentinean folk medicine. It contains nordihydroguaiaretic acid (NDGA), a lignan with nefrotoxic and hepatotoxic effects. The presence of NDGA converts controversial the use of L. divaricata. The amount of NDGA is higher in alcoholic extracts than in aqueous extracts (AE). The last 20 years had a great advance on the use of AE to treat different conditions in a safe manner. In this review, we present the scientific results tending to confirm the potential beneficial effects of the AE on human health. The anti-proliferative effects of AE of L. divaricata have been assayed on a tumor lymphoid line (BW 5147) and the pathways involved in such effects were described. The anti-microbial activity was determined by tests for bacteria and fungus. The anti-inflammatory activity was assayed by using carrageen and TPA induced-inflammation tests. The Immunomodulatory effects were investigated ¯in vivo and ¯in vitro on mice. Sub-fractions of aqueous extracts were obtained and analyzed. The immunogenicity of proteins from crude AE was characterized and antioxidant and nutritional activity were studied. The effect of an AE on hair loss was assayed. In summary, AE from L. divaricata has pharmacological activities including anti-microbial, anti-inflammatory, anti-cancer effects.

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Larrea divaricata Cav. (Jarilla) (Zygophyllaceae) es utilizada en medicina popular Argentina. Contiene ácido nordihidroguaiarético (NDGA), un lignano con efectos nefrotóxicos y hepatotóxicos. La presencia de NDGA hace controvertido el uso de L. divaricata. La cantidad de NDGA es mayor en extractos alcohólicos que en extractos acuosos (EA). Los últimos 20 años han tenido un gran avance en el uso de EA para el tratamiento de diferentes condiciones en forma segura. En esta revisión se presentan resultados científicos que confirman los efectos potencialmente beneficiosos de los EA sobre la salud humana. Los efectos anti-proliferativos se han ensayado en una línea de tumor linfoide, así como los mecanismos involucrados. La actividad anti-microbiana se determinó usando pruebas para bacterias y hongos. La actividad anti-inflamatoria fue evaluada mediante el uso de inflamación inducida por carragenina y TPA. Los efectos inmunomoduladores fueron investigados "in vivo" e "in vitro" en ratones. Sub-fracciones de los EA fueron obtenidos y analizados. La inmunogenicidad de las proteínas del EA crudo se caracterizaron y se estudiaron las actividades antioxidantes nutricionales. Además, se ensayó el efecto del EA en la caída del cabello. En resumen, los EA de L. divaricata presentan actividades farmacológicas como por ejemplo, anti-microbiana, anti-inflamatoria y efectos anti-cancerígenos.

Asunto(s)

Antineoplásicos/farmacología , Extractos Vegetales/farmacología , Larrea/química , Antiinfecciosos , Antiinflamatorios , Argentina

RESUMEN

The flowers of Tilia species have been used in Europe for many years to treat colds, bronchitis, fever, inflammations and influenza. It is well known that lymphocytes play a role in acquired immunity related to pathogens and tumor cells attachment. The aim of this study was to determine the effect of an aqueous (AE) and a dichloromethane extract (DM) from Tilia x viridis which is widely used and distributed in Argentina, on normal murine lymphocyte proliferation after being administered to mice. Both extracts presented a stimulatory effect on normal murine lymphocyte proliferation. The effect exerted by DM was principally related to macrophage activation, meanwhile AE exerted an important direct effect on lymphocytes related to the rutin presence. The stimulating effect, exerted on normal lymphocytes was due to a protective effect of apoptosis and also to cell IL2 production.

Asunto(s)

Proliferación Celular/efectos de los fármacos , Linfocitos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Tilia/química , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Femenino , Flores/química , Factores Inmunológicos/farmacología , Interleucina-2/metabolismo , Ratones , Ratones Endogámicos C3H , Rutina/farmacología

RESUMEN

INTRODUCTION: Larrea divaricata Cav. is a common shrub used in folk medicine to treat a variety of diseases. The main product extracted from this bush is nordihydroguaiaretic acid (NDG), which is a potent antioxidant. OBJECTIVE: In this paper we propose a novel method for the quantification of NDG in different extracts of Larrea divaricata. The concentration of NDG in two different aqueous extracts (I and D) and an ethanolic extract (Eet) was analysed, in order to evaluate the safe use of the extracts for pharmacological purposes. METHODOLOGY: Micellar electrokinetic chromatography (MEKC) was performed under the following conditions: the background electrolyte used consisted of 20 mm phosphate buffer (pH 7.5), 10 mm sodium dodecyl sulphate and 10% acetonitrile. RESULTS: The limits of detection and quantitation of NDG were 4.54 × 10(-4) and 10.6 × 10(-4) mg/mL, respectively. The concentration of this acid in both aqueous extracts was within the safe levels. However, the decoction must be used carefully because the concentration of the acid was almost over the recommended limit. In the case of ethanolic extracts, the amount of NDG was above the safe concentration, which is in agreement with the solubility of the active compound in ethanol. CONCLUSIONS: The conclusions of this study demonstrate that most of these plant extracts should be used with care, especially those which are used with medicinal purposes. This is the first research on the quantification of NDG using MEKC in jarilla extracts.

Asunto(s)

Cromatografía Capilar Electrocinética Micelar/métodos , Larrea/química , Masoprocol/química , Extractos Vegetales/química , Concentración de Iones de Hidrógeno , Estructura Molecular , Hojas de la Planta/química , Tallos de la Planta/química , Reproducibilidad de los Resultados

RESUMEN

Larrea divaricata is a plant widely used in folk medicine in Argentina. It has been demonstrated that an aqueous extract of L. divaricata possesses a biphasic effect on cell proliferation, at low concentrations exerts a stimulatory action and at high concentrations exerts anti-proliferative effects upon the T lymphoma BW 5147; therefore, we propose in this paper to test the effect of the extract 'in vitro' and 'in vivo' in another T-cell lymphoma named EL-4. It was analyzed 'in vitro' cell proliferation by tritiated thymidine uptake and the effect of the extract on tumors induced in mice analyzing tumor progression and survival.The results showed that the aqueous extract induced the proliferation of tumor cells at all the concentrations studied. The results 'in vivo' showed that the aqueous extract stimulated significantly the size of tumors and that untreated mice lived longer than those treated. It is important to be very careful when plant extracts are selected for the treatment of several diseases. Consequently, before using a plant extract, specific scientific studies must be undertaken on different models to certificate therapeutic and adverse effects. Moreover, it can be said that L. divaricata has a specific anti-tumor mechanism of action depending on the targets.

Asunto(s)

Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Larrea/química , Extractos Vegetales/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/uso terapéutico , Argentina , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Interpretación Estadística de Datos , Relación Dosis-Respuesta a Droga , Femenino , Medicina Tradicional , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Análisis de Supervivencia , Resultado del Tratamiento

RESUMEN

Larrea divaricata exerts a dual effect on the proliferation of BW5147 cells. The aim of this work was to analyze the effect of leukotrienes on the antiproliferative action of the extract in relation to cyclic adenosine monophosphate production and protein kinase C activation. The extracts induced cyclic adenosine monophosphate and inhibited protein kinase C but induced leukotriene B4 production, which exerted contrary effects. These results suggest the finding of an extract free of compounds, which can increase leukotriene B4 level, in order to obtain a more active extract to be used in the treatment of lymphomas, positively modulated by leukotrienes.

Asunto(s)

Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , GMP Cíclico/metabolismo , Larrea , Leucotrieno B4/metabolismo , Linfoma de Células T/enzimología , Proteína Quinasa C/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Animales , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Activación Enzimática , Linfoma de Células T/patología , Ratones , Extractos Vegetales/farmacología , Hojas de la Planta , Proteína Quinasa C/metabolismo , Regulación hacia Arriba

RESUMEN

Macrophages are involved in the host defense against infectious pathogens and tumors. Tilia species have been used in folk medicine for the treatment of infectious diseases, previously it was demonstrated that a dichloromethane (DM) extract possess antiproliferative action "in vitro" on a lymphoma cell line. The aim of this work was to study the "in vivo" effect of DM extract upon mice peritoneal macrophages. DM extract-activated macrophages phagocytosis through hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) production (phagocytosis (%): basal 16.93 +/- 0.18, DM extract 25.93 +/- 2.8; H(2)O(2) (M): basal 0.0022 +/- 0.00016, DM extract 0.0036 +/- 0.0005; NO (mM): basal 0.0052 +/- 0.0007, DM extract 0.0099 +/- 0.0004). These actions were mediated by cell superoxide dismutase activation. On the other hand, DM extract decreased tumor necrosis factor alpha but increased interleukin-10 in serum. These results suggest that the modulation activity exerted by the extract on immune system cells could be an important mechanism to acquire resistance to tumors and infectious diseases.

Asunto(s)

Activación de Macrófagos/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Cloruro de Metileno/química , Extractos Vegetales/farmacología , Tilia , Animales , Femenino , Peróxido de Hidrógeno/análisis , Interleucina-10/sangre , Interleucina-6/sangre , Ratones , Ratones Endogámicos C3H , Óxido Nítrico/análisis , Nitritos/análisis , Fagocitosis/efectos de los fármacos , Superóxido Dismutasa/análisis , Factor de Necrosis Tumoral alfa/sangre

RESUMEN

Malassezia furfur is a lipodependent, dimorphic and saprophyte fungus which causes pityriasis versicolor, dandruff and seborrheic dermatitis in humans. The drugs available to treat this fungal infection are few. These drugs are highly toxic and are costly when used in prolonged treatments. For these reasons, it is necessary to find new compounds to treat these infections. Ilex paraguariensis St Hilaire is a plant that grows in Argentina, Brazil and Paraguay. The aim of this study was to evaluate the effect of the aqueous extract of Ilex paraguariensis on the growth of M. furfur. High performance liquid chromatography (HPLC) was employed to identify and isolate compounds of I. paraguariensis and the agar-well diffusion method was used to assess the antifungal activity of the extract. The fungicidal/fungistatic effect was evaluated by the modified Thompson assay. The results demonstrated that the aqueous extract of Ilex paraguariensis (1000 mg/ml) possesses inhibitory activity against M. furfur. This antimalassezial activity was equivalent to 2.7 microg/ml of ketoconazole. Therefore, the topical use of Ilex paraguariensis extract as alternative antifungal agent can be suggested.

Asunto(s)

Antifúngicos/farmacología , Ilex paraguariensis/química , Malassezia/efectos de los fármacos , Extractos Vegetales/farmacología , Antifúngicos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química