Exploring the astonishing beneficial effects of round gourd (Praecitrullus fistulosus) and plant lectins towards cancer: A comprehensive review.

Praecitrullus fistulosus, commonly known as round gourd or tinda, is a remarkable source of bioactive substances like polyphenols, antioxidants, carotene, magnesium, and vitamin C. It is considered one of the Cucurbitaceae family due to its medicinal features. Plant lectins are carbohydrate-binding proteins that can bind and identify the carbohydrate moieties upon cancerous cells demonstrated some anticancer potentials. Several plant lectins are helpful as cancer biomarkers because they can find cancer cells and contribute to cell death initiation via apoptosis and autophagy, suggesting the possible role of cancer-inhibiting pathways. Therefore, round gourd and lectins might be useful in the controlling of cancer. This study compiled the most recent scientific literature regarding the round gourd and numerous plant lectins, and the clinical trials of lectins exploring their effects on cancer were examined. Research according to the literature, round gourd, and lectins demonstrated pharmacological alterations not only in cancer but in many other disorders as well. Thus, clinical investigations proved the beneficial impacts of round gourd and lectins on cancer due to their antioxidants, anti-inflammatory, and anticarcinogenic properties. Further studies are required to fully comprehend the potential applications of these plant-derived compounds against cancer, as well as to identify the round gourd components and clarify their mode of action.

Recent advances in the use of legume lectins for the diagnosis and treatment of breast cancer.

Poor lifestyle choices and genetic predisposition are factors that increase the number of cancer cases, one example being breast cancer, the third most diagnosed type of malignancy. Currently, there is a demand for the development of new strategies to ensure early detection and treatment options that could contribute to the complete remission of breast tumors, which could lead to increased overall survival rates. In this context, the glycans observed at the surface of cancer cells are presented as efficient tumor cell markers. These carbohydrate structures can be recognized by lectins which can act as decoders of the glycocode. The application of plant lectins as tools for diagnosis/treatment of breast cancer encompasses the detection and sorting of glycans found in healthy and malignant cells. Here, we present an overview of the most recent studies in this field, demonstrating the potential of lectins as: mapping agents to detect differentially expressed glycans in breast cancer, as histochemistry/cytochemistry analysis agents, in lectin arrays, immobilized in chromatographic matrices, in drug delivery, and as biosensing agents. In addition, we describe lectins that present antiproliferative effects by themselves and/or in conjunction with other drugs in a synergistic effect.

Peruvian plants of traditional use as potential sources of molecules with activity against COVID-19

RESUMEN Introducción: La situación actual de la COVID-19 es un gran problema para la población humana. En la actualidad, no hay medicamentos curativos disponibles en el mercado. Los investigadores están haciendo todo lo posible para producir fármacos con que luchar contra la enfermedad. Se están considerando varios esfuerzos basados en diferentes orientaciones del conocimiento científico y en las tecnologías para el tratamiento de la enfermedad. Desafortunadamente, ninguno de estos medicamentos funciona absolutamente contra la corriente pandémica. Por lo tanto, las moléculas bioactivas de plantas, animales y microorganismos podrían ser una mejor opción para tratar la COVID-19. Objetivo: Revisar la literatura sobre especies de la flora del Perú utilizadas en el tratamiento de enfermedades respiratorias y destacar las plantas con posible producción de metabolitos secundarios y lectinas vegetales potencialmente útiles como alternativa frente a la COVID-19. Métodos: Se revisaron artículos de literatura científica relacionados con el uso de la medicina tradicional en Perú, China e India para el tratamiento de enfermedades respiratorias, así como la información sobre lectinas vegetales y metabolitos secundarios con potencial utilidad contra la COVID-19. Resultados: Se presenta una amplia relación de géneros y especies de la flora del Perú con gran potencial contra la COVID-19. La mayoría de estas especies pertenecen a las familias Asteraceae, Loranthaceae, Piperaceae, Viscaceae y Zingiberaceae. Numerosas especies son endémicas del Perú. Conclusiones: La flora del Perú tiene más de 22 000 especies de plantas. Muchas de estas especies se utilizan tradicionalmente en el tratamiento de enfermedades respiratorias y pueden ser potencialmente útiles en el tratamiento de la COVID-19.

ABSTRACT Introduction: The current situation of COVID-19 is a big issue for the human population. At present, no healing drug is available in the market. Researchers are doing their best to produce drugs to fight the disease. Various efforts are being considered based on different directions of scientific knowledge and technologies for the treatment of the disease. Unfortunately, none of these drugs works absolutely against the pandemic. Therefore, bioactive molecules from plants, animals and microorganisms could be a better option to treat COVID-19. Objective: Review the literature about species of the flora of Peru used for the treatment of respiratory diseases and highlight the plants with potential in the production of secondary metabolites and plant lectins as an alternative against COVID-19. Methods: A review was conducted of scientific articles related to the use of traditional medicine in Peru, China, and India for the treatment of respiratory diseases, as well as information about plant lectins and secondary metabolites potentially useful against COVID-19. Results: A long list is presented of genera and species of the flora of Peru with great potential against COVID-19. Most of these species belong to the Asteraceae, Loranthaceae, Piperaceae, Viscaceae and Zingiberaceae families. Numerous species are endemic to Peru. Conclusions: The flora of Peru has more than 22 000 plant species. Many of these species are traditionally used in the treatment of respiratory diseases and are potentially useful for the treatment of COVID-19.

Immunomodulatory and anti-infective effects of Cratylia mollis lectin (Cramoll) in a model of wound infection induced by Staphylococcus aureus.

This work evaluated the immunomodulatory and anti-infective effects of Cratylia mollis lectin (Cramoll) in a model of wound infection induced by S. aureus. Swiss mice were divided into 3 groups (n = 12/group): non-inoculated (Control group); inoculated with S. aureus (Sa group); inoculated with S. aureus and treated with Cramoll (Sa + Cramoll group). In each animal, one lesion (64 mm2) was induced on the back and contaminated with S. aureus (~4.0 × 106 CFU/wound). The treatment with Cramoll (5 µg/animal/day) started 1-day post-infection (dpi) and extended for 10 days. Clinical parameters (wound size, inflammatory aspects, etc.) were daily recorded; while cytokines levels, bacterial load and histological aspects were determined in the cutaneous tissue at 4th dpi or 11th dpi. The mice infected with S. aureus exhibited a delay in wound contraction and the highest inflammatory scores. These effects were impaired by the treatment with Cramoll which reduced the release of key inflammatory mediators (TNF-α, NO, VEGF) and the bacterial load at wound tissue. Histological evaluations showed a restauration of skin structures in the animals treated with Cramoll. Taken together, these results provide more insights about the healing and immunomodulatory properties of Cramoll and suggest this lectin as a lead compound for treatment of wound infection.

Lectins applied to diagnosis and treatment of prostate cancer and benign hyperplasia: A review.

Environmental factors, as well as genetic factors, contribute to the increase in prostate cancer cases (PCa), the second leading cause of cancer death in men. This fact calls for the development of more reliable, quick and low-cost early detection tests to distinguish between malignant and benign cases. Abnormal cell glycosylation pattern is a promising PCa marker for this purpose. Proteins, such as lectins can decode the information contained in the glycosylation patterns. Several studies have reported on applications of plant lectins as diagnostic tools for PCa considering the ability to differentiate it from benign cases. In addition, they can be used to detect, separate and differentiate the glycosylation patterns of cells or proteins present in serum, urine and semen. Herein, we present an overview of these studies, showing the lectins that map glycans differentially expressed in PCa, as well as benign hyperplasia (BPH). We further review their applications in biosensors, histochemical tests, immunoassays, chromatography, arrays and, finally, their therapeutic potential. This is the first study to review vegetable lectins applied specifically to PCa.

Leguminosae Lectins as Biological Tools in Medical Research: a Review

Abstract Lectins were discovered first in plants and later in other living things, and nowadays it is known that they are present in almost all many life forms. These proteins can bind to specific carbohydrates, which make them perform a number of biological activities and can be used as tools in the study of glycoconjugate structures present on the cell surface, being effective in medical research. Plant lectins, leguminosae lectins particularly, are among the most studied plant proteins. They are very versatile molecules, which show several interesting biological properties. Thus, the present paper reviewed the advances about the leguminosae lectins biological properties studies in the last ten years, taking into account their possible applications in the fields of Clinical Microbiology, Pharmacy and Cancerology through a search in the electronic databases, providing opportunity to exchange information about the theme. Leguminosae lectins can neutralize pathogenic organisms, be they viruses, prokaryotes and eukaryotes, in addition carcinogenic cells, besides decreasing oxidative stress, conditions which increases the possibility of alternative substances for the design of new drugs to be used in current therapeutic, expanding the possibilities of diseases cure.

Green tea polyphenols mitigate the plant lectins-induced liver inflammation and immunological reaction in C57BL/6 mice via NLRP3 and Nrf2 signaling pathways.

Plant-derived dietary lectins have been reported to be involved in the pathogenesis of several inflammatory diseases, including hepatitis, inflammatory bowel disease, diabetes, and celiac disease. In this present study, we aimed to assess whether green tea polyphenols (GTPs) exerts protective effects against plant lectins-induced liver inflammation and immunological reaction in mice. The C57BL/6 mice received intragastric GTPs (200 mg/kg b.w.) once per day for 7 consecutive days prior to plant lectins stimulation (50 mg/kg b.w., intraperitoneally). GTPs supplementation alleviated the histopathological changes of liver and the disorder of serum biochemical parameters in plant lectins-challenged mice. GTPs supplementation also alleviated plant lectins-induced oxidative stress and liver inflammation, decreasing protein contents and gene expression levels of pro-inflammatory cytokines in the plasma and hepatic tissue and increasing antioxidant capacity in the liver. GTPs decreased the protein expression levels of myeloperoxidase, F4/80 and neutrophil, as determined by immunohistochemical analysis, and T lymphocytes (CD4 and CD8) contents as determined by immunofluorescence analysis, in the liver. Moreover, we found that GTPs inhibited Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome expression and increased nuclear factor erythroid 2-related factor 2 (Nrf2) pathways in the liver tissues of plant lectins-challenged mice. Taken together, these results show that GTPs alleviates hepatic inflammatory damage and immunological reaction after plant lectins challenge, and GTPs (or green tea intake) supplements can be beneficial for people exposed to plant lectins.

Quantum Dot Labelling of Tepary Bean (Phaseolus acutifolius) Lectins by Microfluidics.

Lectins are bioactive proteins with the ability to recognize cell membrane carbohydrates in a specific way. Diverse plant lectins have shown diagnostic and therapeutic potential against cancer, and their cytotoxicity against transformed cells is mediated through the induction of apoptosis. Previous works have determined the cytotoxic activity of a Tepary bean (Phaseolus acutifolius) lectin fraction (TBLF) and its anti-tumorigenic effect on colon cancer. In this work, lectins from the TBLF were additionally purified by ionic-exchange chromatography. Two peaks with agglutination activity were obtained: one of them was named TBL-IE2 and showed a single protein band in two-dimensional electrophoresis; this one was thus selected for coupling to quantum dot (QD) nanoparticles by microfluidics (TBL-IE2-QD). The microfluidic method led to low sample usage, and resulted in homogeneous complexes, whose visualization was achieved using multiphoton and transmission electron microscopy. The average particle size (380 nm) and the average zeta potential (-18.51 mV) were determined. The cytotoxicity of the TBL-IE2 and TBL-IE2-QD was assayed on HT-29 colon cancer cells, showing no differences between them (p ≤ 0.05), where the LC50 values were 1.0 × 10-3 and 1.7 × 10-3 mg/mL, respectively. The microfluidic technique allowed control of the coupling between the QD and the protein, substantially improving the labelling process, providing a rapid and efficient method that enabled the traceability of lectins. Future studies will focus on the potential use of the QD-labelled lectin to recognize tumor tissues.

Automated Image Analyses of Glomerular Hypertrophy in a Mouse Model of Diabetic Nephropathy.

Background: Glomerular hypertrophy is a hallmark of kidney injury in metabolically induced renal diseases such as obesity-associated glomerulopathies and diabetic nephropathy (DN). Methods: Using light sheet fluorescent microscopy (LSFM) and 3D image analysis, we tested algorithms for automated and unbiased quantification of total glomerular numbers and individual glomerular volume in the uninephrectomized (UNx) db/db mouse model of DN. Results: At 6 weeks after surgery, db/db and UNx db/db mice showed increased urine albumin-to-creatinine ratio (ACR) compared with db/+ control mice. Before euthanasia, glomeruli were labeled in vivo by injecting tomato lectin. Whole-kidney LSFM 3D image analysis revealed that mean glomerular volume was significantly increased in UNx db/db mice compared with db/+ mice. Moreover, analysis of individual glomerular volume showed a shift in volume distribution toward larger glomeruli and thereby demonstrated additive effects of diabetes and UNx on induction of glomerular hypertrophy. The automatized quantification showed no significant differences in glomerular numbers among db/+, db/db, and UNx db/db mice. These data correlated with glomerular numbers as quantified by subsequent stereologic quantification. Conclusions: Overall, LSFM coupled with automated 3D histomorphometric analysis was demonstrated to be advantageous for unbiased assessment of glomerular volume and numbers in mouse whole-kidney samples. Furthermore, we showed that injection of fluorescently labeled lectin and albumin can be used as markers of nephron segments in the mouse kidneys, thus enabling functional assessment of kidney physiology, pathology, and pharmacology in preclinical rodent models of kidney disease.

Plant lectins in cancer therapeutics: Targeting apoptosis and autophagy-dependent cell death.

Plant lectins are non-immunoglobin in nature and bind to the carbohydrate moiety of the glycoconjugates without altering any of the recognized glycosyl ligands. Plant lectins have found applications as cancer biomarkers for recognizing the malignant tumor cells for the diagnosis and prognosis of cancer. Interestingly, plant lectins contribute to inducing cell death through autophagy and apoptosis, indicating their potential implication in cancer inhibitory mechanism. In the present review, anticancer activities of major plant lectins have been documented, with a detailed focus on the signaling circuit for the possible molecular targeted cancer therapy. In this context, several lectins have exhibited preclinical and clinical significance, driving toward therapeutic potential in cancer treatment. Moreover, several plant lectins induce immunomodulatory activities, and therefore, novel strategies have been established from preclinical and clinical investigations for the development of combinatorial treatment consisting of immunotherapy along with other anticancer therapies. Although the application of plant lectins in cancer is still in very preliminary stage, advanced high-throughput technology could pave the way for the development of lectin-based complimentary medicine for cancer treatment.

Natural Macromolecules with Protective and Antitumor Activity.

This review summarizes the literature data regarding plant lectins as novel drug sources in the prevention or treatment of cancer. Moreover, such compounds have been described as natural toxins that possess different biological activities (cytotoxic, antitumor, antimutagenic and anticarcinogenic properties). This activity depends greatly on their structure and affinity. Most of the mushroom heterosides are known as ß-glucans with ß-(1→3)-glycosidic bonds. It is thought that their conformation, bonds, molecular size can modulate the immune response by triggering different receptors. The mechanism on normal and tumor cells of various plant and mushroom polysaccharides and lectins is briefly presented in this paper.

Plant Lectins as Medical Tools against Digestive System Cancers.

Digestive system cancers-those of the esophagus, stomach, small intestine, colon-rectum, liver, and pancreas-are highly related to genetics and lifestyle. Most are considered highly mortal due to the frequency of late diagnosis, usually in advanced stages, caused by the absence of symptoms or masked by other pathologies. Different tools are being investigated in the search of a more precise diagnosis and treatment. Plant lectins have been studied because of their ability to recognize and bind to carbohydrates, exerting a variety of biological activities on animal cells, including anticancer activities. The present report integrates existing information on the activity of plant lectins on various types of digestive system cancers, and surveys the current state of research into their properties for diagnosis and selective treatment.

Dairy propionibacteria prevent the proliferative effect of plant lectins on SW480 cells and protect the metabolic activity of the intestinal microbiota in vitro.

Plant lectins are specific carbohydrate-binding proteins that are widespread in legumes such as beans and pulses, seeds, cereals, and many plants used as farm feeds. They are highly resistant to cooking and digestion, reaching the intestinal lumen and/or blood circulation with biological activity. Since many legume lectins trigger harmful local and systemic reactions after their binding to the mucosal surface, these molecules are generally considered anti-nutritive and/or toxic substances. In the gut, specific cell receptors and bacteria may interact with these dietary components, leading to changes in intestinal physiology. It has been proposed that probiotic microorganisms with suitable surface glycosidic moieties could bind to dietary lectins, favoring their elimination from the intestinal lumen or inhibiting their interaction with epithelial cells. In this work, we assessed in vitro the effects of two representative plant lectins, concanavalin A (Con A) and jacalin (AIL) on the proliferation of SW480 colonic adenocarcinoma cells and metabolic activity of colonic microbiota in the absence or presence of Propionibacterium acidipropionici CRL 1198. Both lectins induced proliferation of colonic cells in a dose-dependent manner, whereas ConA inhibited fermentative activities of colonic microbiota. Pre-incubation of propionibacteria with lectins prevented these effects, which could be ascribed to the binding of lectins by bacterial cells since P. acidipropionici CRL 1198 was unable to metabolize these proteins, and its adhesion to colonic cells was reduced after reaction with Con A or AIL. The results suggest that consumption of propionibacteria at the same time as lectins could reduce the incidence of lectin-induced alterations in the gut and may be a tool to protect intestinal physiology.

Ribosome-Inactivating Proteins from Plants: A Historical Overview.

This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs), starting from the first studies at the end of eighteenth century involving the purification of abrin and ricin, as well as the immunological experiments of Paul Erlich. Interest in these plant toxins was revived in 1970 by the observation of their anticancer activity, which has given rise to a large amount of research contributing to the development of various scientific fields. Biochemistry analyses succeeded in identifying the enzymatic activity of RIPs and allowed for a better understanding of the ribosomal machinery. Studies on RIP/cell interactions were able to detail the endocytosis and intracellular routing of ricin, thus increasing our knowledge of how cells handle exogenous proteins. The identification of new RIPs and the finding that most RIPs are single-chain polypeptides, together with their genetic sequencing, has aided in the development of new phylogenetic theories. Overall, the biological properties of these proteins, including their abortifacient, anticancer, antiviral and neurotoxic activities, suggest that RIPs could be utilized in agriculture and in many biomedical fields, including clinical drug development.

Novel interactions of complex carbohydrates with peanut (PNA), Ricinus communis (RCA-I), Sambucus nigra (SNA-I) and wheat germ (WGA) agglutinins as revealed by the binding specificities of these lectins towards mucin core-2 O-linked and N-linked glycans and related structures.

Plant lectins through their multivalent quaternary structures bind intrinsically flexible oligosaccharides. They recognize fine structural differences in carbohydrates and interact with different sequences in mucin core 2 or complex-type N-glycan chain and also in healthy and malignant tissues. They are used in characterizing cellular and extracellular glycoconjugates modified in pathological processes. We study here, the complex carbohydrate-lectin interactions by determining the effects of substituents in mucin core 2 tetrasaccharide Galß1-4GlcNAcß1-6(Galß1-3)GalNAcα-O-R and fetuin glycopeptides on their binding to agarose-immobilized lectins PNA, RCA-I, SNA-I and WGA. Briefly, in mucin core 2 tetrasaccharide (i) structures modified by α2-3/6-Sialyl LacNAc, LewisX and α1-3-Galactosyl LacNAc resulted in regular binding to PNA whereas compounds with 6-sulfo LacNAc displayed no-binding; (ii) strucures bearing α2-6-sialyl 6-sulfo LacNAc, or 6-sialyl LacdiNAc carbohydrates displayed strong binding to SNA-I; (iii) structures with α2-3/6-sialyl, α1-3Gal LacNAc or LewisX were non-binder to RCA-I and compounds with 6-sulfo LacNAc only displayed weak binding; (iv) structures containing LewisX, 6-Sulfo LewisX, α2-3/6-sialyl LacNAc, α2-3/6-sialyl 6-sulfo LacNAc and GalNAc Lewis-a were non-binding to WGA, those with α1-2Fucosyl, α1-3-Galactosyl LacNAc, α2-3-sialyl T-hapten plus 3'/6'sulfo LacNAc displayed weak binding, and compounds with α2-3-sialyl T-hapten, α2.6-Sialyl LacdiNAc, α2-3-sialyl D-Fucß1-3 GalNAc and Fucα-1-2 D-Fucß-1-3GalNAc displaying regular binding and GalNAc LewisX and LacdiNAc plus D-Fuc ß-1-3 GalNAcα resulting in tight binding. RCA-I binds Fetuin triantennary asialoglycopeptide 100 % after α-2-3 and 25 % after α-2-6 sialylation, 30 % after α-1-2 and 100 % after α-1-3 fucosylation, and 50 % after α-1-3 galactosylation. WGA binds 3-but not 6-Fucosyl chitobiose core. Thus, information on the influence of complex carbohydrate chain constituents on lectin binding is apparently essential for the potential application of lectins in glycoconjugate research.

Dietary Plant Lectins Appear to Be Transported from the Gut to Gain Access to and Alter Dopaminergic Neurons of Caenorhabditis elegans, a Potential Etiology of Parkinson's Disease.

Lectins from dietary plants have been shown to enhance drug absorption in the gastrointestinal tract of rats, be transported trans-synaptically as shown by tracing of axonal and dendritic paths, and enhance gene delivery. Other carbohydrate-binding protein toxins are known to traverse the gut intact in dogs. Post-feeding rhodamine- or TRITC-tagged dietary lectins, the lectins were tracked from gut to dopaminergic neurons (DAergic-N) in transgenic Caenorhabditis elegans (C. elegans) [egIs1(Pdat-1:GFP)] where the mutant has the green fluorescent protein (GFP) gene fused to a dopamine transport protein gene labeling DAergic-N. The lectins were supplemented along with the food organism Escherichia coli (OP50). Among nine tested rhodamine/TRITC-tagged lectins, four, including Phaseolus vulgaris erythroagglutinin (PHA-E), Bandeiraea simplicifolia (BS-I), Dolichos biflorus agglutinin (DBA), and Arachis hypogaea agglutinin (PNA), appeared to be transported from gut to the GFP-DAergic-N. Griffonia Simplicifolia and PHA-E, reduced the number of GFP-DAergic-N, suggesting a toxic activity. PHA-E, BS-I, Pisum sativum (PSA), and Triticum vulgaris agglutinin (Succinylated) reduced fluorescent intensity of GFP-DAergic-N. PHA-E, PSA, Concanavalin A, and Triticum vulgaris agglutinin decreased the size of GFP-DAergic-N, while BS-I increased neuron size. These observations suggest that dietary plant lectins are transported to and affect DAergic-N in C. elegans, which support Braak and Hawkes' hypothesis, suggesting one alternate potential dietary etiology of Parkinson's disease (PD). A recent Danish study showed that vagotomy resulted in 40% lower incidence of PD over 20 years. Differences in inherited sugar structures of gut and neuronal cell surfaces may make some individuals more susceptible in this conceptual disease etiology model.

Plant lectins, chemical and biological aspects

Lectins, carbohydrate-binding proteins of non-immune origin, that agglutinate cells or precipitate polysaccharides and glycoconjugates, are well distributed in nature, mainly in the Plant Kingdom. The great majority of the plante lectins are present in seed cotyledons where they are found in the cytoplasm or int he protein bodies, although they have also been found in roots, stems and leaves. Due to their peculiar properties, the lectins are used as a tool both for analytical and preparative purposes in biochemistry, cellular biology, immunology and related areas. In agriculture and medicine the use of lectins greatly improved in the last few years. The lextins, with few exceptions, are glycoproteins, need divalent cations to display full activity and are, in general, oligomers with variable molecular weight. Although the studies on lectins have completed a century, their role in nature is yet ynknown . Several hypotheses on their physiological functions have been suggested. Thus, lectins could play important roles in defense against pathogens, plant-microorganism symbiosis, cell organization, embryo morphogenesis, phagocytosis, cell wall elongation, pollen recognition and as reserve proteins. A brief review on the general properties and roles of the lectins is given.