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1.
Chem Biol Interact ; 399: 111156, 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39029856

RESUMEN

Leishmaniases, caused by Leishmania parasites, are widespread and pose significant health risks globally. Visceral leishmaniasis (VL) is particularly prevalent in Brazil, with high morbidity and mortality rates. Traditional treatments, such as pentavalent antimonials, have limitations due to toxicity and resistance. Therefore, exploring new compounds like lectins is crucial. Concanavalin A (ConA) has shown promise in inhibiting Leishmania growth. This study aimed to evaluate its leishmanicidal effect on L. infantum promastigotes and understand its mechanism of action. In vitro tests demonstrated inhibition of promastigote growth when treated with ConA, with IC50 values ranging from 3 to 5 µM over 24-72 h. This study suggests that ConA interacts with L. infantum glycans. Additionally, ConA caused damage to the membrane integrity of parasites and induced ROS production, contributing to parasite death. Scanning electron microscopy confirmed morphological alterations in treated promastigotes. ConA combined with the amphotericin B (AmB) showed synergistic effects, reducing the required dose of AmB, and potentially mitigating its toxicity. ConA demonstrated no cytotoxic effects on macrophages, instead stimulating their proliferation. These findings reinforce that lectin exhibits promising leishmanicidal activity against L. infantum promastigotes, making ConA a potential candidate for leishmaniasis treatment.


Asunto(s)
Antiprotozoarios , Canavalia , Concanavalina A , Leishmania infantum , Leishmania infantum/efectos de los fármacos , Concanavalina A/farmacología , Animales , Antiprotozoarios/farmacología , Antiprotozoarios/química , Semillas/química , Especies Reactivas de Oxígeno/metabolismo , Ratones , Anfotericina B/farmacología , Lectinas/farmacología , Lectinas/química , Lectinas/metabolismo , Lectinas de Plantas/farmacología , Lectinas de Plantas/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/parasitología
2.
Nutrients ; 16(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39064727

RESUMEN

Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. METHODOLOGY: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. CONCLUSION: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.


Asunto(s)
Adipoquinas , Berberina , Composición Corporal , Gymnema sylvestre , Obesidad , Resistina , Humanos , Masculino , Femenino , Adulto , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Adipoquinas/sangre , Adipoquinas/metabolismo , Composición Corporal/efectos de los fármacos , Persona de Mediana Edad , Berberina/farmacología , Resistina/sangre , Resistina/metabolismo , Apelina , Presión Sanguínea/efectos de los fármacos , Nicotinamida Fosforribosiltransferasa/metabolismo , Citocinas/metabolismo , Citocinas/sangre , Extractos Vegetales/farmacología , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Lectinas , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico
3.
Food Chem Toxicol ; 190: 114815, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38876381

RESUMEN

Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 µg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 µg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC50 = 3.5 µg/mL), KG1 (IC50 = 18.6 µg/mL) and K562 (102.0 µg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 µg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte - HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells.


Asunto(s)
Drosophila melanogaster , Lectinas , Animales , Humanos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Drosophila melanogaster/efectos de los fármacos , Células HL-60 , Lectinas/farmacología , Lectinas/toxicidad , Estrés Oxidativo/efectos de los fármacos
4.
Glycobiology ; 34(7)2024 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-38857376

RESUMEN

Multivalency in lectins plays a pivotal role in influencing glycan cross-linking, thereby affecting lectin functionality. This multivalency can be achieved through oligomerization, the presence of tandemly repeated carbohydrate recognition domains, or a combination of both. Unlike lectins that rely on multiple factors for the oligomerization of identical monomers, tandem-repeat lectins inherently possess multivalency, independent of this complex process. The repeat domains, although not identical, display slightly distinct specificities within a predetermined geometry, enhancing specificity, affinity, avidity and even oligomerization. Despite the recognition of this structural characteristic in recently discovered lectins by numerous studies, a unified criterion to define tandem-repeat lectins is still necessary. We suggest defining them multivalent lectins with intrachain tandem repeats corresponding to carbohydrate recognition domains, independent of oligomerization. This systematic review examines the folding and phyletic diversity of tandem-repeat lectins and refers to relevant literature. Our study categorizes all lectins with tandemly repeated carbohydrate recognition domains into nine distinct folding classes associated with specific biological functions. Our findings provide a comprehensive description and analysis of tandem-repeat lectins in terms of their functions and structural features. Our exploration of phyletic and functional diversity has revealed previously undocumented tandem-repeat lectins. We propose research directions aimed at enhancing our understanding of the origins of tandem-repeat lectin and fostering the development of medical and biotechnological applications, notably in the design of artificial sugars and neolectins.


Asunto(s)
Lectinas , Secuencias Repetidas en Tándem , Animales , Humanos , Lectinas/química , Lectinas/metabolismo
5.
J Toxicol Environ Health A ; 87(14): 592-603, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38712866

RESUMEN

Punica granatum, popularly known as pomegranate, is a fruit tree with wide worldwide distribution, containing numerous phytochemicals of great medicinal value. The aim of the present study was to determine the phytochemical profile and antioxidant potential of a protein fraction (PF) derived from P. granatum sarcotesta which is rich in lectin. In addition, the acute oral toxicity, genotoxicity and antigenotoxicity of this protein fraction (PF) from P. granatum sarcotesta was measured. The phytochemical profile of PF was determined using HPLC. The in vitro antioxidant effect was assessed using the methods of total antioxidant capacity (TAC) and DPPH and ABTS+ radical scavenging. Acute oral toxicity was determined in female Swiss mice administered a single dose of 2000 mg/kg. This PF was examined for genotoxicity and antigenotoxicity at doses of 500, 1000 and 2000 mg/kg, utilizing mouse peripheral blood cells. Phytochemical characterization detected a high content of ellagic acid and antioxidant capacity similar to that of ascorbic acid (positive control). PF was not toxic (LD50 >2000 mg/kg) and did not exert a genotoxic effect in mice. PF protected the DNA of peripheral blood cells against damage induced by cyclophosphamide. In conclusion, this PF fraction exhibited significant antioxidant activity without initiating toxic or genotoxic responses in mice.


Asunto(s)
Antioxidantes , Extractos Vegetales , Granada (Fruta) , Animales , Ratones , Antioxidantes/farmacología , Femenino , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Extractos Vegetales/farmacología , Granada (Fruta)/química , Lectinas/toxicidad , Pruebas de Mutagenicidad , Daño del ADN/efectos de los fármacos , Pruebas de Toxicidad Aguda
6.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38732017

RESUMEN

Intelectins belong to a family of lectins with specific and transitory carbohydrate interaction capabilities. These interactions are related to the activity of agglutinating pathogens, as intelectins play a significant role in immunity. Despite the prominent immune defense function of intelectins, limited information about its structural characteristics and carbohydrate interaction properties is available. This study investigated an intelectin transcript identified in RNA-seq data obtained from the South American lungfish (Lepidosiren paradoxa), namely LpITLN2-B. The structural analyses predicted LpITLN2-B to be a homo-trimeric globular protein with the fibrinogen-like functional domain (FReD), exhibiting a molecular mass of 57 kDa. The quaternary structure is subdivided into three monomers, A, B, and C, and each domain comprises 11 ß-sheets: an anti-parallel ß-sheet, a ß-hairpin, and a disordered ß-sheet structure. Molecular docking demonstrates a significant interaction with disaccharides rather than monosaccharides. The preferential interaction with disaccharides highlights the potential interaction with pathogen molecules, such as LPS and Poly(I:C). The hemagglutination assay inhibited lectins activity, especially maltose and sucrose, highlighting lectin activity in L. paradoxa samples. Overall, our results show the potential relevance of LpITLN2-B in L. paradoxa immune defense against pathogens.


Asunto(s)
Proteínas de Peces , Peces , Inmunidad Innata , Lectinas , Animales , Lectinas/química , Lectinas/metabolismo , Lectinas/inmunología , Lectinas/genética , Peces/inmunología , Peces/genética , Proteínas de Peces/genética , Proteínas de Peces/química , Proteínas de Peces/inmunología , Proteínas de Peces/metabolismo , Simulación del Acoplamiento Molecular , Secuencia de Aminoácidos , Proteínas Ligadas a GPI/química , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/inmunología
7.
J Vet Diagn Invest ; 36(2): 262-268, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38362676

RESUMEN

A flock of 48 sheep in Argentina grazing on a pasture of hybrid Urochloa (formerly Brachiaria) Mulato II (Urochloa ruziziensis × Urochloa decumbens × Urochloa brizantha) developed facial dermatitis, severe jaundice, and weakness after brief physical activity. Blood biochemistry of 3 animals revealed azotemia, elevated aspartate aminotransferase activity, and increased direct, indirect, and total bilirubin concentrations. The urine was markedly turbid and contained large concentrations of bile pigments and protein. At autopsy of 2 animals, there was severe jaundice and subcutaneous submandibular edema. The livers were enlarged, intensely yellow, and had a marked acinar pattern. Gallbladders were distended, and the kidneys were diffusely dark in one animal and yellow-green in the other. Microscopically, there was lymphoplasmacytic and histiocytic cholangiohepatitis with abundant crystals in the lumen of bile ducts and in the cytoplasm of macrophages. The proximal and distal convoluted renal tubules had protein casts in their lumens, and crystals were observed in the lumen and epithelial cells. Lectin histochemistry showed strong affinity for Arachis hypogaea agglutinin in hepatic macrophages. In the one sheep that was tested for heavy metals, copper concentrations in the liver and kidney were within the RIs. Despite the immediate change of pasture, morbidity and mortality were 100% within 3 mo. The association between the consumption of this pasture, and the clinical, biochemical, pathology, and lectin histochemistry findings confirmed intoxication with Urochloa hybrid Mulato II. To our knowledge, intoxication by this hybrid of Urochloa has not been reported previously.


Asunto(s)
Brachiaria , Ictericia , Enfermedades de las Ovejas , Ovinos , Animales , Argentina , Poaceae , Brachiaria/química , Hígado/patología , Ictericia/patología , Ictericia/veterinaria , Riñón , Lectinas , Enfermedades de las Ovejas/patología
8.
Curr Protein Pept Sci ; 25(6): 443-453, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38284715

RESUMEN

Lectins are proteins widely distributed among plants, animals and microorganisms that have the ability to recognize and interact with specific carbohydrates. They have varied biological activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses and protozoa, which is related to the interaction of these proteins with the carbohydrates present in the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases caused by protozoa of the genus Leishmania. In vitro and in vivo tests with promastigotes and amastigotes of Leishmania demonstrated that lectins have the ability to interact with glycoconjugates present on the cell surface of the parasite, it prevents their development through various mechanisms of action, such as the production of ROS and alteration of membrane integrity, and can also interact with defense cells present in the human body, thus showing that these molecules can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity, emphasizing the advances and perspectives of research in this theme. Through the analysis of the selected studies, we were able to conclude that lectins have great potential for inhibiting the development of leishmaniasis. However, there are still few studies on this subject.


Asunto(s)
Lectinas , Leishmania , Leishmaniasis , Leishmania/efectos de los fármacos , Humanos , Lectinas/farmacología , Lectinas/química , Lectinas/metabolismo , Leishmaniasis/tratamiento farmacológico , Leishmaniasis/parasitología , Animales , Antiprotozoarios/farmacología , Antiprotozoarios/química , Especies Reactivas de Oxígeno/metabolismo
9.
Biosensors (Basel) ; 14(1)2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38248411

RESUMEN

Pap smear screening is a widespread technique used to detect premalignant lesions of cervical cancer (CC); however, it lacks sensitivity, leading to identifying biomarkers that improve early diagnosis sensitivity. A characteristic of cancer is the aberrant sialylation that involves the abnormal expression of α2,6 sialic acid, a specific carbohydrate linked to glycoproteins and glycolipids on the cell surface, which has been reported in premalignant CC lesions. This work aimed to develop a method to differentiate CC cell lines and primary fibroblasts using a novel lectin-based biosensor to detect α2,6 sialic acid based on attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and chemometric. The biosensor was developed by conjugating gold nanoparticles (AuNPs) with 5 µg of Sambucus nigra (SNA) lectin as the biorecognition element. Sialic acid detection was associated with the signal amplification in the 1500-1350 cm-1 region observed by the surface-enhanced infrared absorption spectroscopy (SEIRA) effect from ATR-FTIR results. This region was further analyzed for the clustering of samples by applying principal component analysis (PCA) and confidence ellipses at a 95% interval. This work demonstrates the feasibility of employing SNA biosensors to discriminate between tumoral and non-tumoral cells, that have the potential for the early detection of premalignant lesions of CC.


Asunto(s)
Nanopartículas del Metal , Lectinas de Plantas , Proteínas Inactivadoras de Ribosomas , Sambucus nigra , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Lectinas , Ácido N-Acetilneuramínico , Oro , Línea Celular
10.
Mol Biotechnol ; 66(2): 288-299, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37097521

RESUMEN

Lectins are proteins that reversibly bind to carbohydrates and are commonly found across many species. The Banana Lectin (BanLec) is a member of the Jacalin-related Lectins, heavily studied for its immunomodulatory, antiproliferative, and antiviral activity. In this study, a novel sequence was generated in silico considering the native BanLec amino acid sequence and 9 other lectins belonging to JRL. Based on multiple alignment of these proteins, 11 amino acids of the BanLec sequence were modified because of their potential for interference in active binding site properties resulting in a new lectin named recombinant BanLec-type Lectin (rBTL). rBTL was expressed in E. coli and was able to keep biological activity in hemagglutination assay (rat erythrocytes), maintaining similar structure with the native lectin. Antiproliferative activity was demonstrated on human melanoma lineage (A375), evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT). rBTL was able to inhibit cellular growth in a concentration-dependent manner, in an 8-h incubation, 12 µg/mL of rBTL led to a 28.94% of cell survival compared to cell control with 100%. Through a nonlinear fit out log-concentration versus biological response, an IC50% of 3.649 µg/mL of rBTL was determined. In conclusion, it is possible to state that the changes made to the rBTL sequence maintained the structure of the carbohydrate-binding site without changing specificity. The new lectin is biologically active, with an improved carbohydrate recognition spectrum compared to nBanLec, and can also be considered cytotoxic for A375 cells.


Asunto(s)
Escherichia coli , Lectinas , Humanos , Animales , Ratas , Lectinas/genética , Lectinas/farmacología , Escherichia coli/genética , Lectinas de Plantas/genética , Lectinas de Plantas/farmacología , Lectinas de Plantas/química , Secuencia de Aminoácidos , Carbohidratos
11.
An Acad Bras Cienc ; 95(suppl 2): e20220619, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38088730

RESUMEN

A new lectin from marine sponge Ircinia strobilina, denominated IsL, was isolated by combination of affinity chromatography in Guar gum matrix followed by size exclusion chromatography. IsL was able to agglutinate native and enzymatically treated rabbit erythrocytes, being inhibited by galactosides, such as α-methyl-D-galactopyranoside, ß-methyl-D-galactopyranoside and α-lactose. IsL hemagglutinating activity was stable at neutral to alkaline pH, however the lectin loses its activity at 40° C. The molecular mass determinated by mass spectrometry was 13.655 ± 5 Da. Approximately 40% of the primary structure of IsL was determined by mass spectrometry, but no similarity was observed with any protein. The secondary structure of IsL consists of 28% α-helix, 26% ß-sheet, and 46% random region, as determined by dichroism circular. IsL was a calcium-dependent lectin, but no significant variations were observed by circular dichroism when IsL was incubated in presence of calcium and EDTA. IsL was not toxic against Artemia nauplii and did not have antimicrobial activity against bacterial cells. However, the IsL was able to significantly inhibit the biofilm formation of Staphylococcus aureus and Staphylococcus epidermidis.


Asunto(s)
Lectinas , Poríferos , Animales , Conejos , Lectinas/farmacología , Galactosa/metabolismo , Galactosa/farmacología , Calcio/metabolismo , Biopelículas
12.
Int J Mol Sci ; 24(21)2023 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-37958949

RESUMEN

Cells use glycans to encode information that modulates processes ranging from cell-cell recognition to programmed cell death. This information is encoded within a glycocode, and its decoding is performed by carbohydrate-binding proteins. Among these, lectins stand out due to their specific and reversible interaction with carbohydrates. Changes in glycosylation patterns are observed in several pathologies, including cancer, where abnormal glycans are found on the surfaces of affected tissues. Given the importance of the bioprospection of promising biomolecules, the current work aimed to determine the structural properties and anticancer potential of the mannose-specific lectin from seeds of Canavalia villosa (Cvill). Experimental elucidation of the primary and 3D structures of the lectin, along with glycan array and molecular docking, facilitated the determination of its fine carbohydrate-binding specificity. These structural insights, coupled with the lectin's specificity, have been combined to explain the antiproliferative effect of Cvill against cancer cell lines. This effect is dependent on the carbohydrate-binding activity of Cvill and its uptake in the cells, with concomitant activation of autophagic and apoptotic pathways.


Asunto(s)
Canavalia , Lectinas , Lectinas/farmacología , Lectinas/análisis , Canavalia/metabolismo , Simulación del Acoplamiento Molecular , Lectinas de Plantas/metabolismo , Semillas/metabolismo , Carbohidratos/análisis , Polisacáridos/análisis
13.
Protein Pept Lett ; 30(12): 1048-1057, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38018205

RESUMEN

OBJECTIVES: The present study investigated the anti-depressive-like (anti-immobility) effect of a lectin from Moringa oleifera seeds (WSMoL) in mice. METHODS: To evaluate an acute effect, the animals were treated with WSMoL (1, 2, and 4 mg/kg, i.p.) 30 min before the tail suspension test (TST). To investigate the involvement of monoaminergic and nitrergic signaling, the mice were pre-treated with selective antagonists. The role of the WSMoL carbohydrate-recognizing domain (CRD) was verified using previous blockage with casein (0.5 mg/mL). The subacute anti-immobility effect was also evaluated by administering WSMoL (1, 2, and 4 mg/kg, i.p.) once a day for 7 d. Finally, an open field test (OFT) was performed to identify possible interferences of WSMoL on animal locomotory behavior. RESULTS: WSMoL reduced the immobility time of mice in the TST at all doses, and combined treatment with fluoxetine (5 mg/kg, i.p.) and WSMoL (1 mg/kg) was also effective. The CRD appeared to be involved in the anti-immobility effect since the solution of WSMoL (4 mg/kg) pre-incubated with casein showed no activity. The lectin effect was prevented by the pre-treatment of mice with ketanserin, yohimbine, and SCH 23390, thereby demonstrating the involvement of monoaminergic pathways. In contrast, pre-treatment with L-NAME, aminoguanidine, and L-arginine did not interfere with lectin action. WSMoL exhibited a subacute effect in the TST, thereby reducing immobility time and increasing agitation time even on the seventh day. OFT data revealed that the anti-immobility effect was not caused by interference with locomotor behavior. CONCLUSION: WSMoL elicits an anti-depressant-like effect that is dependent on monoaminergic signaling.


Asunto(s)
Lectinas , Moringa oleifera , Animales , Ratones , Agua , Caseínas , Semillas
14.
Curr Pharm Des ; 29(33): 2618-2625, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37933218

RESUMEN

There is increasing pressure for innovative methods to treat compromised and difficult-to-heal wounds. Consequently, new strategies are needed for faster healing, reducing infection, hydrating the wound, stimulating healing mechanisms, accelerating wound closure, and reducing scar formation. In this scenario, lectins present as good candidates for healing agents. Lectins are a structurally heterogeneous group of glycosylated or non-glycosylated proteins of non-immune origin, which can recognize at least one specific monosaccharide or oligosaccharide specific for the reversible binding site. Cell surfaces are rich in glycoproteins (glycosidic receptors) that potentially interact with lectins through the number of carbohydrates reached. This lectin-cell interaction is the molecular basis for triggering various changes in biological organisms, including healing mechanisms. In this context, this review aimed to (i) provide a comprehensive overview of relevant research on the potential of vegetable lectins for wound healing and tissue regeneration processes and (ii) discuss future perspectives.


Asunto(s)
Lectinas de Plantas , Piel , Humanos , Piel/patología , Cicatrización de Heridas , Cicatriz/patología , Lectinas
15.
Toxicon ; 234: 107306, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37778740

RESUMEN

WSMoL, a water-soluble lectin from the seeds of Moringa oleifera, present several biological activities. This work aimed to evaluated the toxicity and antitumor activity of WSMoL. To analyze toxicity, it was determined hematological, biochemical and histological parameters; consumption of water and feed as well as the weight of the animals. Antitumor analysis included evaluation of tumor weight, histology and cytokine levels. Acute toxicity assay revealed 60% mortality of animals treated with lectin at 200 mg/kg i. p. At 100 mg/kg i. p., the animals showed a decreased food and water consumption as well weight gain in comparison with control. However, no animal died and there were no alterations in blood parameters or histological analysis. Antitumor activity evaluated at safe doses (2.5, 5 and 10 mg/kg) showed a significant reduction in tumor weight. Tumor photomicrographs evidenced that WSMoL treatment reduced dissemination of tumor cells. WSMoL (5 and 10 mg/kg) significantly enhance the immune function in the tumor environment as showed by increased the levels of pro-inflammatory (TNF-α, IFN-γ, IL-2, IL-6, and IL-17) and anti-inflammatory (IL-4 and IL-10) cytokines. In conclusion, WSMoL showed in vivo antitumor activity in mice bearing sarcoma 180 tumor, probably by increase the immune response against the tumor.


Asunto(s)
Moringa oleifera , Sarcoma 180 , Animales , Ratones , Lectinas , Agua , Sarcoma 180/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidad , Citocinas , Semillas
16.
Braz J Biol ; 83: e274635, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37851772

RESUMEN

This study evaluated the insecticidal activity of crude extracts from Enterolobium contortisiliquum (Vell.) seeds on eggs and larvae of A. aegypti, and also verified the phytochemical profile and the presence of lectins in the extract. The 0.15 M NaCl saline solution was used as the extracting substance. For tests with eggs and larvae, the crude extract was used in its raw form (RCE) and boiled at 100º C for 5 min (BCE). Concentrations of 4.68; 9.37; 18.75; 28.13; 37.13 and 46.89 mg/mL, with distilled water as a negative control. Assays were performed in triplicate. The results were subjected to analysis of variance, Tukey's test and Log-Probit analysis to determine LC50 and LC90. BCE showed better results on eggs than RCE, managing to prevent the hatching of larvae in 81.66% ± 10.40 of treated eggs, at a concentration of 46.89 mg/mL. The LC50 and LC90 were set at 35.95 and 52.67 mg/mL, respectively. In tests with larvae, concentrations of 46.89 and 37.13 mg/mL, for RCE and BCE, caused 100% mortality in 24 hours of exposure. Larval mortality at the other concentrations increased with exposure time extending to 48 h. RCE, at 48 h exposure is the most promising extract on larvae (E = 72.77%, LC90 = 10.86 mg/mL). In RCE, the presence of lectins and secondary metabolites: flavonoids, xanthones and phenols, were detected. The results demonstrate the potential of E. contortisiliquum seed extracts with ovicidal and larvicidal action on A. aegypti.


Asunto(s)
Aedes , Anopheles , Fabaceae , Insecticidas , Animales , Insecticidas/farmacología , Solución Salina/análisis , Extractos Vegetales/química , Semillas , Larva , Fitoquímicos/análisis , Lectinas/análisis
17.
Acta Parasitol ; 68(4): 869-879, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37874484

RESUMEN

PURPOSE: The treatment of leishmaniasis, an anthropozoonosis caused by Leishmania protozoa, is limited by factors, such as adverse effects, toxicity, and excessive cost, which has highlighted the importance of novel drugs. In this context, natural products have been considered as sources of antileishmanial agents. This study investigated the leishmanicidal activity of Microgramma vacciniifolia frond lectin (MvFL) on promastigotes and amastigotes of Leishmania amazonensis. METHODS: The effects of MvFL on promastigote proliferation and macrophage infection by amastigotes were evaluated and mean inhibitory concentrations (IC50) were calculated. As a safety assessment, the hemolytic capacity of MvFL (6.25-200 µg/mL) against mouse and human erythrocytes was determined. Additionally, the ability of MvFL (6.25-100 µg/mL) to modulate lysosomal and phagocytic activities and the nitric oxide (NO) production by murine peritoneal macrophages was also investigated. RESULTS: After 24 h, MvFL inhibited the proliferation of L. amazonensis promastigotes, with an IC50 of 88 µg/mL; however, hemolytic activity was not observed. MvFL also reduced macrophage infection by amastigotes with an IC50 of 52 µg/mL. Furthermore, treatment with MvFL reduced the number of amastigotes internalized by infected murine peritoneal macrophages by up to 68.9% within 48 h. At a concentration of 25 µg/mL, MvFL stimulated lysosomal activity of macrophages within 72 h, but did not alter phagocytic activity or induce NO production at any of the tested concentrations. CONCLUSION: MvFL exerts antileishmanial activity and further studies are needed to assess its therapeutic potential in in vivo experimental models of leishmaniasis.


Asunto(s)
Antiprotozoarios , Leishmania mexicana , Leishmania , Leishmaniasis , Humanos , Animales , Ratones , Lectinas/farmacología , Macrófagos , Leishmaniasis/tratamiento farmacológico , Antiprotozoarios/farmacología , Ratones Endogámicos BALB C
18.
Viruses ; 15(9)2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37766292

RESUMEN

The SARS-CoV-2 entry into host cells is mainly mediated by the interactions between the viral spike protein (S) and the ACE-2 cell receptor, which are highly glycosylated. Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the in vitro anti-SARS-CoV-2 activity of two mannose-binding lectins isolated from the Brazilian plants Canavalia brasiliensis and Dioclea violacea (ConBR and DVL). These lectins inhibited SARS-CoV-2 Wuhan-Hu-1 strain and variants Gamma and Omicron infections, with selectivity indexes (SI) of 7, 1.7, and 6.5, respectively for ConBR; and 25, 16.8, and 22.3, for DVL. ConBR and DVL inhibited over 95% of the early stages of the viral infection, with strong virucidal effect, and also protected cells from infection and presented post-entry inhibition. The presence of mannose resulted in the complete lack of anti-SARS-CoV-2 activity by ConBR and DVL, recovering virus titers. ATR-FTIR, molecular docking, and dynamic simulation between SARS-CoV-2 S and either lectins indicated molecular interactions with predicted binding energies of -85.4 and -72.0 Kcal/Mol, respectively. Our findings show that ConBR and DVL lectins possess strong activities against SARS-CoV-2, potentially by interacting with glycans and blocking virus entry into cells, representing potential candidates for the development of novel antiviral drugs.


Asunto(s)
Antivirales , COVID-19 , Humanos , Antivirales/farmacología , Lectinas de Unión a Manosa , SARS-CoV-2 , Simulación del Acoplamiento Molecular , Lectinas/farmacología
19.
Glycobiology ; 33(11): 855-860, 2023 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-37584473

RESUMEN

Cell surface glycans play essential roles in diverse physiological and pathological processes and their assessment has important implications in biomedicine and biotechnology. Here we present a rapid, versatile, and single-step multicolor flow cytometry method for evaluation of cell surface glycan signatures using a panel of selected fluorochrome-conjugated lectins. This procedure allows simultaneous detection of cell surface glycans with a 10-fold reduction in the number of cells required compared with traditional multistep lectin staining methods. Interestingly, we used this one-step lectin array coupled with dimension reduction algorithms in a proof-of-concept application for discrimination among different tumor and immune cell populations. Moreover, this procedure was also able to unveil T-, B-, and myeloid cell subclusters exhibiting differential glycophenotypes. Thus, we report a rapid and versatile lectin cytometry method to simultaneously detect a particular repertoire of surface glycans on living cells that can be easily implemented in different laboratories and core facilities.


Asunto(s)
Colorantes Fluorescentes , Lectinas , Lectinas/metabolismo , Polisacáridos/metabolismo , Membrana Celular/metabolismo
20.
J Appl Microbiol ; 134(7)2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37437916

RESUMEN

AIMS: We investigated the putative fungistatic and fungicidal activities of pomegranate sarcotesta lectin (PgTeL) against Cryptococcus neoformans B3501 (serotype D), specifically the ability of PgTeL to inhibit yeast capsule and biofilm formation in this strain. METHODS AND RESULTS: PgTeL showed a minimum inhibitory concentration of 172.0 µg ml-1, at which it did not exhibit a fungicidal effect. PgTeL concentrations of 4.0-256.0 µg ml-1 reduced biofilm biomass by 31.0%-64.0%. Furthermore, 32.0-256.0 µg ml-1 PgTeL decreased the metabolic activity of the biofilm by 32.0%-93.0%. Scanning electron microscopy images clearly revealed disruption of the biofilm matrix. Moreover, PgTeL disrupted preformed biofilms. At concentrations of 8.0-256.0 µg ml-1, PgTeL reduced metabolic activity in C. neoformans by 36.0%-92.0%. However, PgTeL did not inhibit the ability of B3501 cells to form capsules under stress conditions. CONCLUSIONS: PgTeL inhibited biofilm formation and disrupted preformed biofilms, demonstrating its potential for use as an anticryptococcal agent.


Asunto(s)
Criptococosis , Cryptococcus neoformans , Granada (Fruta) , Lectinas/farmacología , Granada (Fruta)/metabolismo , Plancton/metabolismo , Biopelículas , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Antifúngicos/metabolismo
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