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1.
Int Immunopharmacol ; 129: 111615, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38330799

RESUMEN

Maclurin is a natural phenolic compound isolated from Morus alba(white mulberry) andGarcinia mangostana (purple mangosteen) and has been reported to regulate cancer progression, oxidative stress, and melanogenesis. The regulatory role of maclurin, however, has never been demonstrated. This study investigated in vitro and in vivo anti-inflammatory roles of maclurin and the underlying mechanism in caspase-11 non-canonical inflammasome-stimulated inflammatory responses in macrophages and an animal model of acute lethal sepsis. Maclurin protected J774A.1 macrophages from LPS-induced cytotoxicity and suppressed caspase-11 non-canonical inflammasome-stimulated pyroptosis. Maclurin decreased the secretion and mRNA expression of pro-inflammatory cytokines and inflammatory mediators, such as IL-1ß, IL-18, TNF-α, IL-6, nitric oxide (NO), and inducible NO synthase (iNOS) in caspase-11 non-canonical inflammasome-stimulated J774A.1 macrophages. Mechanistic studies revealed that maclurin markedly suppressed the proteolytic activation of caspase-11 and gasdermin D (GSDMD) in caspase-11 non-canonical inflammasome-stimulated J774A.1 macrophages, while it did not inhibit caspase-11-mediated direct sensing of LPS. In vivo study revealed that maclurin ameliorated acute lethal sepsis in mice by increasing the survival rate and decreasing the serum levels of IL-1ß and IL-18 without significant toxicity. In conclusion, this study suggests that maclurin is a novel anti-inflammatory agent in inflammatory responses and against acute lethal sepsis via the inhibition of the caspase-11 non-canonical inflammasome in macrophages, which justifies its potential as an anti-inflammatory therapeutic agent in traditional medicine.


Asunto(s)
Inflamasomas , Lectinas de Plantas , Sepsis , Animales , Ratones , Inflamasomas/metabolismo , Caspasas/metabolismo , Interleucina-18/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Antiinflamatorios/farmacología
2.
Int J Mol Sci ; 25(2)2024 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-38279312

RESUMEN

Serum and plasma exhibit a broad dynamic range of protein concentrations, posing challenges for proteome analysis. Various technologies have been developed to reduce this complexity, including high-abundance depletion methods utilizing antibody columns, extracellular vesicle enrichment techniques, and trace protein enrichment using nanobead cocktails. Here, we employed lectins to address this, thereby extending the scope of biomarker discovery in serum or plasma using a novel approach. We enriched serum proteins using 37 different lectins and subjected them to LC-MS/MS analysis with data-independent acquisition. Solanum tuberosum lectin (STL) and Lycopersicon esculentum lectin (LEL) enabled the detection of more serum proteins than the other lectins. STL and LEL bind to N-acetylglucosamine oligomers, emphasizing the significance of capturing these oligomer-binding proteins when analyzing serum trace proteins. Combining STL and LEL proved more effective than using them separately, allowing us to identify over 3000 proteins from serum through single-shot proteome analysis. We applied the STL/LEL trace-protein enrichment method to the sera of systemic lupus erythematosus model mice. This revealed differences in >1300 proteins between the systemic lupus erythematosus model and control mouse sera, underscoring the utility of this method for biomarker discovery.


Asunto(s)
Lupus Eritematoso Sistémico , Solanum lycopersicum , Solanum tuberosum , Animales , Ratones , Proteoma , Solanum tuberosum/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Lectinas de Plantas/metabolismo , Lectinas/metabolismo , Proteínas Sanguíneas , Biomarcadores
3.
Anticancer Drugs ; 34(10): 1085-1093, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37823283

RESUMEN

Every food source contains both edible and inedible waste components. Millions of tonnes of trash from the food business are made from fruits, and these wastes are containing higher-value medicinal components, such as alkaloids, flavonoids, phenolic contents, a huge amount of proteins and secondary metabolites. These bioactive phytoconstituents are being used for the treatment of many serious fatal diseases. So, utilizing the recovered bioactive molecules from food wastes as functional ingredients offers a long-term alternative source of therapeutically active components that will lead to the discovery of novel phytoconstituents or novel treatment approaches. The goal of this systematic study is to provide an overview of the jackfruit (Artocarpus heterophyllus Lam, Moraceae) edible byproducts, such as jackfruit seeds that are largely neglected. This seed contains numerous bioactive lead molecules, such as carbohydrate-binding protein jacalin, which exhibits potent anticancer activity against colon cancer, blood cancer and breast cancer as well as can enlighten the new possible treatment approaches in targeted therapy and photodynamic chemotherapy. Moreover, jackfruit waste seed can be taken as a dietary food, which is having property to prevent and treat cancer and other lifestyle diseases. The works that have been carried out to utilize jackfruit waste other than the juicy edible bulbs have been reviewed in this article.


Asunto(s)
Artocarpus , Lectinas , Humanos , Lectinas/análisis , Lectinas/química , Artocarpus/química , Lectinas de Plantas/análisis , Semillas/química
4.
J Chromatogr A ; 1677: 463292, 2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-35853426

RESUMEN

The ability to reversibly bind carbohydrates is an incredible property from lectins. Such characteristic has led these molecules to be employed in several applications involving medical research and biotechnology. Generally, these proteins follow several steps towards purification. Here, the synthesis, physical characterization, and use of levan-coated magnetite nanoparticles (MNPs-levan) for lectin isolation is described. Canavalia ensiformis and Cratylia mollis were used as sources of Concanavalin A and Cramoll, respectively, that were purified by using MNPs-levan. Mass spectrometry, SDS-PAGE, and hemagglutinating activity were employed to assess the efficiency of the process. Moreover, by using mass spectrometry approaches, a novel lectin, similar to Canavalin, was also identified for C. mollis, corroborating the advantages of using nanoparticles over microparticles. MNPs-levan could also be recycled, making this a low-cost, scalable process that can be efficiently employed over crude samples.


Asunto(s)
Fabaceae , Nanopartículas de Magnetita , Fabaceae/química , Óxido Ferrosoférrico , Fructanos , Lectinas/análisis , Lectinas/química , Extractos Vegetales/análisis , Lectinas de Plantas/química , Plantas/metabolismo , Semillas/química
5.
Protein Pept Lett ; 29(6): 555-566, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35538837

RESUMEN

BACKGROUND: Garlic (Allium sativum) from the family Amaryllidaceae is widely used in culinary and is reported to have potential anticancer, anti-diabetic, antimicrobial, and cardioprotective activities. Allium sativum agglutinin (ASA) is a bulb-type lectin (BTL) domaincontaining lectin isolated from garlic and has been studied for its various biological functions. Previous studies have reported the anti-cancer effects of ASA on histiocytic lymphoma (U937), promyelocytic leukemia (HL60), and oral cancer (KB). METHODS: In this study, we have purified and characterized ASA and evaluated it for its anticancer effects on other cancer cell lines. MTT assay and FACS analysis was done to corroborate the anticancer findings against cervical (HeLa) and lung cancer (A549) cell lines. RESULTS: IC50 value of 37 µg/ml in HeLa and a weak activity (26.4 ± 1.9% cellular inhibition at 100µg/ml treatment) in A549 were found in the MTT assay. FACS analysis further corroborated these findings and showed the apoptotic effects of ASA in these cell lines. CONCLUSION: Anticancer activity for members of bulb-type lectin (BTL) domain-containing lectins has been widely reported, and we hope that our study forms a basis for the development of ASA as a therapeutic agent.


Asunto(s)
Productos Biológicos , Ajo , Aglutininas/farmacología , Antioxidantes , Ajo/metabolismo , Lectinas , Lectinas de Plantas/metabolismo , Lectinas de Plantas/farmacología
6.
Lett Appl Microbiol ; 74(5): 777-786, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35100449

RESUMEN

Artocarpin-rich extract (ARE) was prepared using a green technology and standardized to contain 49·6% w/w artocarpin, while lawsone methyl ether was prepared using a green semi-synthesis. ARE, LME and ampicillin exhibited weak anti-MRSA activity with the MICs of 31·2-62·5 µg/ml. Based on the checkerboard assay, the synergistic interaction between ARE (0·03 µg/ml) and LME (0·49 µg/ml) against four MRSA isolates were observed with the fractional inhibitory concentration index (FICI) value of 0·008, while those of ARE (1·95-7·81 µg/ml) and ampicillin (0·49 µg/ml) as well as LME (0·49-1·95 µg/ml) and ampicillin (0·49 µg/ml) were 0·016-0·257. The time kill confirmed the synergistic interactions against MRSA with different degrees. The combination of ARE and LME as well as its combinations with ampicillin altered the membrane permeability of MRSA, which led to release of the intracellular materials. In addition, each compound inhibited the biofilm formation of standard MRSA (DMST 20654) and the clinical isolate (MRSA 1096). These findings suggested that cocktails containing ARE and LME might be used to overcome problems associated with MRSA. Additionally, the results implied that combination of either ARE or LME with available conventional antibiotic agents might be effective in countering these perilous pathogens.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Ampicilina/farmacología , Antibacterianos/farmacología , Biopelículas , Sinergismo Farmacológico , Lectinas de Unión a Manosa , Pruebas de Sensibilidad Microbiana , Naftoquinonas , Extractos Vegetales/farmacología , Lectinas de Plantas
7.
Z Naturforsch C J Biosci ; 77(1-2): 57-63, 2022 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-34105319

RESUMEN

The emergence of antibacterial resistance has significantly increased. Pseudomonas aeruginosa is associated with nosocomial infection and difficult to control. Artocarpin, a flavonoid from Artocarpus heterophyllus Lam. exhibits several pharmacological properties including antibacterial. The study was performed to evaluate interaction between artocarpin and antibiotics including tetracycline against P. aeruginosa. Its mechanism of action on membrane permeability was also investigated. Broth microdilution was conducted for the susceptibility assay. The interaction of artocarpin and antibiotics was evaluated using checkerboard method, the effect on alteration of membrane cell was investigated using bacteriolysis and the released of 260 nm materials. Artocarpin showed moderate to weak activity against the Gram-negative bacteria including P. aeruginosa with MIC values in the range of 31.25-250 µg/mL. A synergistic effect against P. aeruginosa was produced by the combination of artocarpin (31.25 µg/mL) and tetracycline (1.95 µg/mL) with FICI of 0.37. The time-killing assay showed that artocarpin enhance the antibacterial activity of tetracycline against P. aeruginosa by completely inhibiting the bacterial growth. Additionally, the mixture of artocarpin (31.25 µg/mL) and tetracycline (1.95 µg/mL) disrupted membrane permeability and lead to cell death. These results proposed that the combination of artocarpin and tetracycline may be used to overcome P. aeruginosa infection.


Asunto(s)
Extractos Vegetales , Pseudomonas aeruginosa , Antibacterianos/farmacología , Lectinas de Unión a Manosa , Pruebas de Sensibilidad Microbiana , Permeabilidad , Lectinas de Plantas , Tetraciclinas
8.
Biomed Pharmacother ; 146: 112507, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34891122

RESUMEN

Lectins or clusters of carbohydrate-binding proteins of non-immune origin are distributed chiefly in the Plantae. Lectins have potent anti-infectivity properties for several RNA viruses including SARS-CoV-2. The primary purpose of this review is to review the ability of lectins mediated potential biotherapeutic and bioprophylactic strategy against coronavirus causing COVID-19. Lectins have binding affinity to the glycans of SARS-COV-2 Spike glycoprotein that has N-glycosylation sites. Apart from this, the complement lectin pathway is a "first line host defense" against the viral infection that is activated by mannose-binding lectins. Mannose-binding lectins deficiency in serum influences innate immunity of the host and facilitates infectious diseases including COVID-19. Our accumulated evidence obtained from scientific databases particularly PubMed and Google Scholar databases indicate that mannose-specific/mannose-binding lectins (MBL) have potent efficacies like anti-infectivity, complement cascade induction, immunoadjuvants, DC-SIGN antagonists, or glycomimetic approach, which can prove useful in the strategy of COVID-19 combat along with the glycobiological aspects of SARS-CoV-2 infections and antiviral immunity. For example, plant-derived mannose-specific lectins BanLac, FRIL, Lentil, and GRFT from red algae can inhibit and neutralize SARS-CoV-2 infectivity, as confirmed with in-vitro, in-vivo, and in-silico assessments. Furthermore, Bangladesh has a noteworthy resource of antiviral medicinal plants as well as plant lectins. Intensifying research on the antiviral plant lectins, adopting a glyco-biotechnological approach, and with deeper insights into the "glycovirological" aspects may result in the designing of alternative and potent blueprints against the 21st century's biological pandemic of SARS-CoV-2 causing COVID-19.


Asunto(s)
Antivirales/uso terapéutico , Terapia Biológica/métodos , COVID-19/prevención & control , Erradicación de la Enfermedad/métodos , Lectinas de Plantas/uso terapéutico , SARS-CoV-2/efectos de los fármacos , Animales , Antivirales/aislamiento & purificación , Antivirales/farmacología , Terapia Biológica/tendencias , COVID-19/epidemiología , Erradicación de la Enfermedad/tendencias , Humanos , Lectinas de Plantas/aislamiento & purificación , Lectinas de Plantas/farmacología
9.
Future Microbiol ; 16: 1289-1301, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34689597

RESUMEN

COVID-19, caused by the SARS-CoV-2 outbreak, has resulted in a massive global health crisis. Bioactive molecules extracted or synthesized using starting material obtained from marine species, including griffithsin, plitidepsin and fingolimod are in clinical trials to evaluate their anti-SARS-CoV-2 and anti-HIV efficacies. The current review highlights the anti-SARS-CoV-2 potential of marine-derived phytochemicals explored using in silico, in vitro and in vivo models. The current literature suggests that these molecules have the potential to bind with various key drug targets of SARS-CoV-2. In addition, many of these agents have anti-inflammatory and immunomodulatory potentials and thus could play a role in the attenuation of COVID-19 complications. Overall, these agents may play a role in the management of COVID-19, but further preclinical and clinical studies are still required to establish their role in the mitigation of the current viral pandemic.


Asunto(s)
Antivirales/farmacología , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Océanos y Mares , SARS-CoV-2/efectos de los fármacos , Alcaloides/farmacología , Antiinflamatorios , Antivirales/química , Depsipéptidos , Clorhidrato de Fingolimod/química , Clorhidrato de Fingolimod/farmacología , Humanos , Lectinas , Biología Marina , Simulación del Acoplamiento Molecular , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Ficocianina/farmacología , Fitoquímicos , Lectinas de Plantas/química , Lectinas de Plantas/farmacología , Polifenoles/farmacología , Polisacáridos/farmacología , Algas Marinas , Sesquiterpenos/farmacología
10.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3551-3559, 2021 Jul.
Artículo en Chino | MEDLINE | ID: mdl-34402277

RESUMEN

Viscum plants,the evergreen perennial parasitic shrubs or subshrubs,are mainly distributed in tropical and subtropical regions. There are about 70 Viscum species around the world,including 11 species and one variety in China. Mistletoe lectins are typeⅡ ribosome-inactivating proteins( RIPs) extracted from Viscum plants with anticancer and immunoregulatory activities. Many studies have focused on the mistletoe lectins isolated from V. album in Europe and V. album var. coloratum distributed in South Korea,respectively,and several preparations,such as Iscucin Ⓡ,were developed and clinically applied for cancer treatment. Although Viscum plants are widely distributed in China,only a few studies of mistletoe lectins have been reported. The recent progress of mistletoe lectins was reviewed from extraction,purification,quantitative/qualitative detection,molecular structure,pharmacological activities,toxicities,and clinical application,aiming at providing a reference for in-depth research and utilization of mistletoe lectins produced in China.


Asunto(s)
Toxinas Biológicas , Viscum , Humanos , Lectinas , Extractos Vegetales , Lectinas de Plantas , Proteínas de Plantas/genética
11.
Emerg Microbes Infect ; 10(1): 1519-1529, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34278967

RESUMEN

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern. S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants. Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay. The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1. Lentil lectin also showed antiviral activity against SARS-CoV and MERS-CoV. We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection. Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity. Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment. This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.


Asunto(s)
Antivirales/farmacología , Lens (Planta)/química , Extractos Vegetales/farmacología , Lectinas de Plantas/farmacología , SARS-CoV-2/efectos de los fármacos , Animales , Antivirales/química , Humanos , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/química , Lectinas de Plantas/química , SARS-CoV-2/crecimiento & desarrollo , Semillas/química
12.
Front Immunol ; 12: 582556, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34262553

RESUMEN

Introduction: Several months ago, Chinese authorities identified an atypical pneumonia in Wuhan city, province of Hubei (China) caused by a novel coronavirus (2019-nCoV or SARS-CoV-2). The WHO announced this new disease was to be known as "COVID-19". Evidence Acquisition: Several approaches are currently underway for the treatment of this disease, but a specific cure remains to be established. Evidence Synthesis: This review will describe how the use of selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients. Conclusions: Even if a specific and effective cure for COVID-19 still has some way to go, selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients.


Asunto(s)
COVID-19/complicaciones , COVID-19/prevención & control , Suplementos Dietéticos , SARS-CoV-2 , Berberina/uso terapéutico , COVID-19/epidemiología , COVID-19/virología , China/epidemiología , Ácidos Grasos Omega-3/uso terapéutico , Polisacáridos Fúngicos/uso terapéutico , Humanos , Lactoferrina/uso terapéutico , Minerales/uso terapéutico , Lectinas de Plantas/uso terapéutico , Polifenoles/uso terapéutico , Alimentos de Soja , Vitaminas/uso terapéutico
13.
Molecules ; 26(9)2021 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-34066878

RESUMEN

Plant lectins are widely used in medical glycosciences and glycotechnology. Many lectin-based techniques have been applied for the detection of disease-associated glycans and glycoconjugates. In this study, Butea monosperma agglutinin (BMA), a lectin purified from seeds of the medicinal plant Butea monosperma, was used for the detection of cholangiocarcinoma (CCA)-associated glycans. Expression of BMA-binding N-acetyl galactosamine/galactose (GalNAc/Gal)-associated glycan (BMAG) in CCA tissues was determined using BMA lectin histochemistry; the results showed that BMAG was undetectable in normal bile ducts and drastically increased in preneoplastic bile ducts and CCA. The study in hamsters showed that an increase of BMAG was associated with carcinogenesis of CCA. Using an in-house double BMA sandwich enzyme-linked lectin assay, BMAG was highly detected in the sera of CCA patients. The level of serum BMAG in CCA patients (N = 83) was significantly higher than non-CCA controls (N = 287) and it was applicable for diagnosis of CCA with 55.4% sensitivity, 81.9% specificity, and 76.0% accuracy. A high level of serum BMAG (≥82.5 AU/mL) was associated with unfavorable survival of CCA patients; this information suggested the potential of serum BMAG as a poor prognostic indicator of CCA. In summary, BMAG was aberrantly expressed in preneoplastic bile ducts and CCA, it was also highly detected in patient serum which potentially used as a marker for diagnosis and prognostic prediction of CCA.


Asunto(s)
Aglutininas/metabolismo , Neoplasias de los Conductos Biliares/sangre , Neoplasias de los Conductos Biliares/diagnóstico , Butea/química , Colangiocarcinoma/sangre , Colangiocarcinoma/diagnóstico , Extractos Vegetales/metabolismo , Lectinas de Plantas/metabolismo , Polisacáridos/metabolismo , Animales , Neoplasias de los Conductos Biliares/patología , Biomarcadores de Tumor/sangre , Colangiocarcinoma/patología , Cricetinae , Modelos Animales de Enfermedad , Femenino , Histocitoquímica/métodos , Humanos , Masculino , Persona de Mediana Edad , Plantas Medicinales/química , Pronóstico , Semillas/química
14.
Neurobiol Aging ; 105: 1-15, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34004491

RESUMEN

The age-related loss of GABA in the inferior colliculus (IC) likely plays a role in the development of age-related hearing loss. Perineuronal nets (PNs), specialized aggregates of extracellular matrix, increase with age in the IC. PNs, associated with GABAergic neurotransmission, can stabilize synapses and inhibit structural plasticity. We sought to determine whether PN expression increased on GABAergic and non-GABAergic IC cells that project to the medial geniculate body (MG). We used retrograde tract-tracing in combination with immunohistochemistry for glutamic acid decarboxylase and Wisteria floribunda agglutinin across three age groups of Fischer Brown Norway rats. Results demonstrate that PNs increase with age on lemniscal and non-lemniscal IC-MG cells, however two key differences exist. First, PNs increased on non-lemniscal IC-MG cells during middle-age, but not until old age on lemniscal IC-MG cells. Second, increases of PNs on lemniscal IC-MG cells occurred on non-GABAergic cells rather than on GABAergic cells. These results suggest that synaptic stabilization and reduced plasticity likely occur at different ages on a subset of the IC-MG pathway.


Asunto(s)
Envejecimiento/patología , Neuronas GABAérgicas/patología , Neuronas GABAérgicas/fisiología , Colículos Inferiores/citología , Colículos Inferiores/patología , Red Nerviosa/patología , Red Nerviosa/fisiopatología , Tálamo/citología , Tálamo/patología , Animales , Vías Auditivas/fisiología , Cuerpos Geniculados/citología , Cuerpos Geniculados/patología , Glutamato Descarboxilasa/metabolismo , Pérdida Auditiva/etiología , Pérdida Auditiva/patología , Masculino , Lectinas de Plantas , Ratas , Receptores N-Acetilglucosamina
15.
Sci Rep ; 11(1): 6854, 2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33767225

RESUMEN

Colorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLC-MS-DAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 µg/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-γ) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Artocarpus/química , Colitis/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Extractos Vegetales/farmacología , Madera/química , Animales , Azoximetano/toxicidad , Colitis/inducido químicamente , Colitis/patología , Neoplasias Colorrectales/patología , Citocromo P-450 CYP2C9/química , Citocromo P-450 CYP2C9/metabolismo , Células HCT116 , Humanos , Masculino , Lectinas de Unión a Manosa/química , Ratones , Ratones Endogámicos C57BL , Lectinas de Plantas/química
16.
Plant Cell Rep ; 40(4): 707-721, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33634360

RESUMEN

KEY MESSAGE: Second generation Bt insecticidal toxin in comibination with Allium sativum leaf agglutinin gene has been successfully expressed in cotton to develop sustainable resistance against major chewing and sucking insects. The first evidence of using the Second-generation Bt gene in combination with Allium sativum plant lectin to develop sustainable resistance against chewing and sucking insects has been successfully addressed in the current study. Excessive use of Bt δ-endotoxins in the field is delimiting its insecticidal potential. Second-generation Bt Vip3Aa could be the possible alternative because it does not share midgut receptor sites with any known cry proteins. Insecticidal potential of plant lectins against whitefly remains to be evaluated. In this study, codon-optimized synthetic Bt Vip3Aa gene under CaMV35S promoter and Allium sativum leaf agglutinin gene under phloem-specific promoter were transformed in a local cotton variety. Initial screening of putative transgenic cotton plants was done through amplification, histochemical staining and immunostrip assay. The mRNA expression of Vip3Aa gene was increased to be ninefold in transgenic cotton line L6P3 than non-transgenic control while ASAL expression was found to be fivefold higher in transgenic line L34P2 as compared to non-transgenic control. The maximum Vip3Aa concentration was observed in transgenic line L6P3. Two copy numbers in homozygous form at chromosome number 9 and one copy number in hemizygous form at chromosome number 10 was observed in transgenic line L6P3 through fluorescent in situ hybridization. Significant variation was observed in transgenic cotton lines for morphological characteristics, whereas physiological parameters of plants and fiber characteristics (as assessed by scanning electron microscopic) remained comparable in transgenic and non-transgenic cotton lines. Leaf-detach bioassay showed that all the transgenic lines were significantly resistant to Helicoverpa armigera showing mortality rates between 78% and 100%. Similarly, up to 95% mortality of whiteflies was observed in transgenic cotton lines when compared with non-transgenic control lines.


Asunto(s)
Proteínas Bacterianas/genética , Gossypium/genética , Insectos , Lectinas de Plantas/genética , Plantas Modificadas Genéticamente/fisiología , Aglutininas/genética , Animales , Fibra de Algodón , Productos Agrícolas/genética , Productos Agrícolas/fisiología , Ajo/genética , Dosificación de Gen , Gossypium/fisiología , Hemípteros , Control de Insectos , Mariposas Nocturnas , Regiones Promotoras Genéticas
17.
Molecules ; 27(1)2021 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-35011235

RESUMEN

Phytochemical investigation of Artocarpus chama stem was performed by chromatographic techniques, resulting from the isolation and structure elucidation of three new compounds, namely 3'-farnesyl-apigenin (1), 3-(hydroxyprenyl) isoetin (2), and 3-prenyl-5,7,2',5'-tetrahydroxy-4'-methoxyflavone (3), and five known compounds, namely homoeriodictyol (4), isocycloartobilo-xanthone (5), artocarpanone (6), naringenin (7), and artocarpin (8). From the screening result, A. chama extract showed a potent tyrosinase inhibitory effect. Ihe isolated compounds 1, 4 and 6 also exhibited tyrosinase inhibition with IC50 of 135.70, 52.18, and 38.78 µg/mL, respectively. Moreover, compounds 3, 4, 5, 6, and 8 showed strong activity against Staphylococcus epidermidis, S. aureus, methicillin-resistant S. aureus, and Cutibacterium acnes. This study is the first report on phytochemical investigation with new compounds and biological activities of A. chama. Skin infection can cause dark spots or hyperpigmentation. The isolated compounds that showed both anityrosinase and antimicrobial activities will be further studied in in vivo and clinical trials in order to develop treatment for hyperpigmentation, which is caused by infectious diseases by microorganisms.


Asunto(s)
Antibacterianos/química , Artocarpus/química , Flavonas/química , Extractos Vegetales/química , Tallos de la Planta/química , Antibacterianos/farmacología , Evaluación Preclínica de Medicamentos , Flavanonas/química , Flavonas/farmacología , Humanos , Lectinas de Unión a Manosa/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Extractos Vegetales/farmacología , Lectinas de Plantas/química , Prenilación , Staphylococcus epidermidis/efectos de los fármacos , Xantonas/química
18.
J Biomol Struct Dyn ; 39(13): 4907-4922, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32568615

RESUMEN

Therapeutically important chitin-binding lectins have been already reported in the literature for Solanum tuberosum and Solanum lycopersicum, but their structural data are unavailable. Therefore, we have done comparative structural and functional analysis of chitin-binding lectins from S. tuberosum (STL) and S. lycopersicum (SLL). From the sequence analysis, it has been observed that there is high percentage of proline residues in STL and SLL, 21% and 30% respectively. We utilized the hybrid homology modeling-ab initio approaches to predict the 3D structures of STL and SLL, which are used for in silico interaction studies with N,N'-Diacetylchitobiose, Triacetylchitotriose and Tetra-N-acetylglucosamine. The best STL-glycan and SLL-glycan complexes were subjected to Molecular dynamics simulation to understand and compare the structural stability and the binding patterns of glycans toward STL and SLL. We observed that the structural stability of the STL and SLL had been improved significantly due to the binding of glycans. Together with the results of global, essential dynamics and MM-PBSA analysis, indicated that N,N'-Diacetylchitobiose has more binding affinity towards STL, whereas Triacetylchitotriose has more binding affinity with SLL. This comprehensive and comparative structural and functional analysis provides critical insights about the structures and their binding sites, binding orientation, and binding affinity of chitin oligomers towards the structures of STL and SLL. These findings can be used to design further experimental studies to explore the potential therapeutic properties of STL and SLL. Communicated by Ramaswamy H. Sarma.


Asunto(s)
Lectinas , Solanum , Sitios de Unión , Quitina , Lectinas/metabolismo , Lectinas de Plantas/metabolismo , Solanum/metabolismo
19.
Food Chem ; 340: 128198, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33032147

RESUMEN

In this study, potential of dielectric-barrier discharge (DBD) plasma treatment (40 kV, 12 kHz at 1, 2, 3 and 4 min) to eliminate soybean agglutinin (SBA) activity was investigated in a SBA model system and soymilk. The plasma treatment decreased the SBA in the model system and hemagglutination activity was decreased by 87.31%. SDS-PAGE analysis confirmed the degradation of the SBA polypeptide chain. The multi-spectroscopic analysis revealed a two-stage structure alteration in the SBA upon exposure to the plasma treatment. Oxidation of NH-/NH2- at the peptide bond disrupted the hydrogen bonds and altered the secondary structure of SBA. Further oxidation of aromatic amino acid, cleavage of peptide bonds and the breakage of polypeptide led to the SBA fragmentation and complete unfolding of the protein. The SBA inactivation by the plasma treatment was confirmed in soymilk. Plasma treatment is a promising technology for the elimination of SBA in soybean product.


Asunto(s)
Lectinas de Plantas/química , Gases em Plasma/química , Proteínas de Soja/química , Impedancia Eléctrica , Enlace de Hidrógeno , Oxidación-Reducción , Estructura Secundaria de Proteína , Leche de Soja/química
20.
Artículo en Chino | WPRIM | ID: wpr-888006

RESUMEN

Viscum plants,the evergreen perennial parasitic shrubs or subshrubs,are mainly distributed in tropical and subtropical regions. There are about 70 Viscum species around the world,including 11 species and one variety in China. Mistletoe lectins are typeⅡ ribosome-inactivating proteins( RIPs) extracted from Viscum plants with anticancer and immunoregulatory activities. Many studies have focused on the mistletoe lectins isolated from V. album in Europe and V. album var. coloratum distributed in South Korea,respectively,and several preparations,such as Iscucin Ⓡ,were developed and clinically applied for cancer treatment. Although Viscum plants are widely distributed in China,only a few studies of mistletoe lectins have been reported. The recent progress of mistletoe lectins was reviewed from extraction,purification,quantitative/qualitative detection,molecular structure,pharmacological activities,toxicities,and clinical application,aiming at providing a reference for in-depth research and utilization of mistletoe lectins produced in China.


Asunto(s)
Humanos , Lectinas , Extractos Vegetales , Lectinas de Plantas , Proteínas de Plantas/genética , Toxinas Biológicas , Viscum
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