Plant as a plenteous reserve of lectin

Abstract

Lectins are clusters of glycoproteins of nonimmune foundation that combine specifically and reversibly to carbohydrates, mainly the sugar moiety of glycoconjugates, resulting in cell agglutination and precipitation of glycoconjugates. They are universally distributed in nature, being established in plants, fungi, viruses, bacteria, crustacea, insects, and animals, but leguminacae plants are rich source of lectins. The present review reveals the structure, biological properties, and application of plant lectins.

Introduction

Lectins are omnipresent proteins that are possibly there in all eukaryotic and numerous bacterial species as well as in several viruses. They play a vital function in the plants resistance against insect pests and have been found to be deadly to viruses, bacteria, fungi, insects, and prominent animals. Lectins are sugar-binding proteins that are extremely specific for their sugar molecules. They are carbohydrate-binding proteins of non-immune temperament.^1,2 Lectins are extensively dispersed in nature and ample in plants (Table 1). Lectins are established in diverse species of major taxonomical groups and most of as seed storage proteins.^3,4 It is usually thought that the initial report of a lectin was given by Peter Stillmark.⁵ First lectin to be purified on a large scale and accessible on a trade basis is concanavalin A. Lectins also originated in vegetative organs like roots, leaves, rhizomes, bulbs, tubers, corms, stems, bark, flowers, fruits, phloem sap, latex, and nectar.^6,7 Plant lectins possess analogous biological activities and chemical properties.⁸ Lectins authenticate composite association and dissociation reactions, which is manifold form of the same lectins this is called as isolectin, e.g., lentil,⁹ soybean,¹⁰ garden pea,¹¹ wheat germ,¹² Griffonia simplicifolia,¹³ Viccia graminae,¹⁴ Madura pomifera,¹⁵ Hura crepitans,¹⁶ Psophocarpus tetragonolobus,¹⁷ and Abrus precatorius.¹⁸

Table 1. Listing of plant lectins.

Lectin icon	Lectin name		Source
ConA	Concanavalin A		Canavalia ensiformis
GNA	Snowdrop lectin		Galanthus nivalis
RCA	Ricinus communis Agglutinin,		Ricinus communis
AIL	Jacalin		Artocarpus integrifolia
VVL	Hairy vetch lectin		Vicia villosa
WGA	Wheat Germ agglutinin		Triticum vulgaris
SNA	Elderberry lectin		Sambucus nigra
MAL	Maackia amurensis leukoagglutinin		Maackia amurensis
MAH	Maackia amurensis hemoagglutinin		Maackia amurensis
UEA	Ulex europaeus agglutinin		Ulex europaeus
PNA		Peanut agglutinin	Arachis hypogaea
LCH		Lentil lectin	Lens culinaris
GalPhL		Galactose specific lectin	Phaseolus lunatus
ManPSL		Mannose specific lectin	Pisum sativum
GalDBL		Galactose specific lectin	Dolichos biflorus
GalCaL		Galactose specific lectin	Caragana arborescens

A variety of the plant lectins reveals the ribosome inactivating property that depurinates the rRNA, thus deleterious ribosomes and arresting the protein synthesis^19,20 are called as Ribosome Inactivating proteins (RIPs). The physiological, biochemical, cellular, and molecular characteristics of lectin show its involvement in plant defense mechanism. Lectins are steady over broad pH range, by means of resistant to insect and animal proteases.^21,22

The plant lectins combine to glycoconjugates of other organisms.²³ Plant lectin has capability to detect molecules in a cell, among cells, or organisms. Lectin has physiological roles to recognize nitrogen-fixing bacteria at the surface of roots and transport of sugars, hormones, and glycoproteins.^24,25 Legumes lectins are one of the chief lectin families out of 70 lectins were reported. The legume lectins are a family of carbohydrate binding lectins found in the seeds of plants belonging to the Fabacaea family. The accurate role of the legume lectins in vivo is unknown but they are perhaps implicated in the defense of plants against predators.²⁶

Structure of Plant Lectin

The secondary structure of legume lectin is characterized by 2 anti-parallel β sheets and the presence of strongly bound calcium and manganese ions. In β strands of legume lectin aspatate and aspargine amino acid are highly conserved; these 2 particular amino acids play important role in carbohydrate recognition and participate in hydrogen bonding with the sugar.²⁷

The finest advanced structure of legume lectin is that of concanavaline A (Figure 1). The quaternary structure of concanavalin A is having tetrameric form.²⁸ The quaternary structure of lectins form complex with cell surfaces and matrix glycoconjugates. It contains multiple binding sites, which play important role in the biological activities of plant lectins. The number of vander Waals and hydrogen bonding involve in the dimmers formation. This 2 dimmer rotate in the different angle to each other and shows the different hydrogen bonding scheme on the dimmer–dimmer interface.²⁹

Figure 1. Structure of concanavaline A Canavalia ensiformis.

Biological Properties of Lectins

Lectins has very important role in biomedical research. Lectins are used in expansive applications such as agglutination, mitogenic stimulation, toxicity to cells, inhibition of fungal, bacterial, and viral growth, insecticidal property, anti-HIV property, anti-cancer and nuclease like activity.^30-32 Application of lectin in the biomedical field are mitogenic activity on human lymphocytes,³³ antifungal activity,³⁴ and activity against the human cancer cell.³⁵ The lectin from Moringa oleifera seeds show coagulant properties, antioxidant activity, and antimicrobial properties.³⁶ The biological possessions of lectins are as follows:

Agglutination

Agglutination is the most effortlessly measurable manifestation of the interface of a lectin with lymphocytes cells. This technique used to identify the occurrence of lectin in a biological source. The aptitude of lectin to agglutinate lymphocytes cells are useful to discriminate between lectins and other sugar binding macromolecules. Agglutination arises while lectin bounds and forms multiple cross bridges among lymphocytes cells. The lectins are blood group specific. The lectins isolated from Sophora japonica, Calpumea aurea, and Dolichos biflorus show specificity to Blood group A and B and Lectin from Erythrina velutina seeds is A, B, and O blood group-specific.^37-39 Lectin extracted from Iris amara is M blood group specific and Vicia graminae and Bauhinia purpurea lectins are N blood group specific, while Parkia javanica lectin agglutinates RBC of rabbit and rat.^40,41 Haemagglutinating activity of the lectin for human erythrocytes increases when crosslinking of soybean agglutination with glutaraldehyde takes place.⁴²

Mitogenic stimulation of lymphocytes

The earliest mitogenic activity of lectin was demonstrated in PHA from Phaseolus vulgaris. The ordinary spectacular effects in the interface of lectins with lymphocytes cells is mitogenic stimulation, it means that occurrence of dormant, non-dividing lymphocytes from the situation of development and propagation.⁴³ Concanavaline-A found to be the first lectin mitogen whose activity might be eagerly inhibited in a reversible way by low concentrations of simple sugars. A number of lectins have been accepted to have mitogenic activity, which includes Wistaria floribunda, Hura crepitans, Lathyrus sativus, Abrus precatorius, and all of these mitogens are inhibited by simple sugars.^44-46

WGA, formerly considered as a non-mitogenic lectin, under appropriate conditions stimulates obviously both human B-lymphocytes⁴⁷ and T-lymphocytes.⁴⁸

Induction of suppressor cells

Lectins are competent to provoke the suppressor lymphocytes cells that deter the activities of both T and B-cells. The aptitude to build up suppressor cell activity leading the conduct with Con A, in humans seems to be a variety of normal lymphoid cells. The production of suppressor cells is reduces in side-line blood lymphocytes of patients with immunodeficiency diseases. Lectins offer a basis for using the measurement of mitogen-induced suppressor cell activity as a suitable clinical test for assessing the level of the immune fitness of patients.⁴²

Toxicity

There are a number of lectins viz. Con A, WGA, PHA, and the lectin from Robinia pseudoacacia are toxic to mammalian cells both in vitro and in vivo.⁴⁹ In meticulous, transformed cells are normally much more sensitive to the cytotoxic effects of lectins than normal cells. The lectins like ricin, abrin, and modeccine are toxic and move down through neuronal processes to the cell body where they inactivate ribosomes resulting in neuronal death.⁵⁰ The defensive effect of ricin,^51,52 Con A,⁵³ and Griffonia simplicifolia lectin⁵⁴ against tumor growth in experimental animals has been depicted. The shielding effect of ricin and abrin in humans against tumor growth and in grouping with anticancer drugs has also been illustrated.^46,55

Cytotoxicity

The phenomenon, lectin dependent cytotoxicity, can be explained by interaction of lectin with killing of target cells by cytotoxic T-lymphocytes through the specific recognition by the affected cells, mediated by lectin. The mitogenic lectins encompasses no immune specificity to both effected and target cells.^56,57 The lectins do not participate in the intercellular recognition, but modifying the surface of the target cells.⁵⁸ Lectins from wheat germ, Ghffonia simplicifolia, hold the capacity to mediate carbohydrate explicit binding of mouse macrophages and tumor cells and to induce killing of the tumor cells by the macrophages.^59,60 Lectin mediated cytotoxicity may take place in vivo, by intraperitoneal injection of Griffonia simplicifolia.⁶¹

Lectin Phagocytosis

The precise identification concerning phagocytes and their targets can be consummate by using lectins on the surface of cell that unite with definite sugar on the surface of another cell resembling a lock and key model. This type of acknowledgment has been termed as lectinophagocytosis.⁶² WGA noticeably increases the binding and phagocytosis of bacteria such as Staphylococcus aureus H, Staphylococcus albus, and Micrococcus luteus. Ingestion of the bacteria take place through an encapsulated E. coli cells when attached to human polymorphonuclear leukocytes by bridging with Con A.⁶³

The antifungal activity

Plant lectins binding to carbohydrates present on the surface of the fungal cell wall is promising. The chitin-binding lectins projected to have a role in the plant's protection against fungi from stinging nettle (Urtica dioica) inhibited the growth of Botrytis cinerea, Trickoderma kamatum, and Pkycomyces blakesleeanus.⁶⁴ WGA inhibited spore germination and hyphal growth of Trichoderma viride which designate that lectin is vital defense protein in plants.⁶⁵ The plant lectins ease can be considered fungicidal proteins are the chimerolectins well in to the class I chitinases.⁶⁶ A number of lectins has been purified and many of lectin shows antifungal activity (Table 2).

Table 2. Lectins and inhibited fungi.

Source of lectin	Fungal species inhibited
Amaranthus viridis	Botrytis cinerea, Fusarium oxysporum
Astragalus mongholicus	Borrytis cinerea, Colletrichum sp, Droschslara turia, Fusarium oxysporum
Capparis spinosa	Valsa mali
Capsicum frutescens	Aspergillus flavus, Fusarium moniliforme
Curcuma amarissima	Colectrotrichum cassiicola, Exserohilum turicicum, Fusarium oxysporum
Dendrobium findlayanum	Alternaria alternata, Colletrichum
Phaselous vulgaris	Mycosphaerella arachidicola
Phaseolus coccineus seeds	Gibberalla sanbinetti, Helminthosporium maydis, Rhizoctonia solani, Sclerotinia sclerotiorum
Pouteria torta	Saccharomyces carevisiae, C. musae, Fusarium oxysporum
Talisia esculenta	Microsporum canis
Withania somnifera	Fusarium moniliforme, Macrophomina phaseolina

The antiviral activity

The plant lectins contribution in inhibiting the viral infection has reported by Balzarini et al., 1992.⁶⁷ A amount of plant lectins are persuasive inhibitors in vitro of animal and human viruses, which have glycoproteins in their virions. The first report of lectin as a antiviral drug is that D-mannose-specific lectin from Gerardia savaglia to prevent infection of H9 cells with human immunodeficiency virus (HIV)-1. The lectin inhibited syncytium formation in the HTLV and HIV-1 by reacting with the oligosaccharide side chains of the HIV-1 gp120 envelop molecule.⁶⁸

Lectins like concanavalin A, wheat germ agglutinin, Lens culinaris agglutinin, Vicia faba agglutinin, Pisum sativum agglutinin, and phytohaem (erythro) agglutinin were found to bind to gp120. They were able to inhibit fusion of HIV-infected cells with CD4 cells by a carbohydrate-specific interaction with the HIV-infected cells.⁶⁹ Plant lectins exhibited anti-coronaviral activity, especially mannose-binding lectins, in severe acute respiratory syndrome coronavirus.⁷⁰ Banana (Musa acuminata) lectin inhibited HIV replication.⁷¹ Extra long autumn purple bean lectin⁷² and mushroom Russula delica lectin⁷³ are capable to inhibit HIV-1 reverse transcriptase. Lectin is able to inhibit HIV-1 reverse transcriptase. Consequently, lectins are potential drugs for treatment of AIDS. Some plant lectins may have an indirect antiviral role.⁷⁴

The antibacterial activity

The main function of lectin to prevent microorganism into the cytoplasm and involve in plant defense mechanism. Lectins play vital role in the plant’s defense against bacteria; it is the indirect mechanism that based on interactions of lectin with cell wall carbohydrates or extracellular glycans.⁷⁵ The second indirect defense mechanism of lectin is the blocking of the movements of normally motile bacteria at the air-water interface by the Datura stramonium seed lectin.⁷⁶ The binding of plant lectins to bacterial cell wall peptidoglycans reveals that lectins strongly interact with muramic acid, N-acetylmuramic acid, and muramyl dipeptide, lectins involve in the plant's defense against microbes.⁷⁷ The cell wall of bacteria can recognized the glycoconjugates and carbohydrate-binding proteins on their membrane. The many strains of E. histolytica express a surface lectin that are immunogenic. This lectin is linked by disulfide bonds and is required for adherence to human intestinal epithelial cells and contact-dependent killing of immune effector cells.⁷⁸ Dietary lectins may also affect the intestinal flora,⁷⁹ and bacterial lectins in turn can activate intestinal cells^80,81 suggested that the b-galactoside binding lectin present in the granular glands around keratinocytes and proposed that skin lectins might mediate mechanisms associated with host defense. Riera et al.⁸² detected b-galactoside-binding lectins from Bufo arenarum skin. The antibacterial activity of these lectins may provide an effective defense against invading microbes in the amphibian Bufo arenarum.

The anti-insect activity

Lectins attach to the glycan receptors there on the surface facing the insect gut to influence the survival and growth of insect pests.⁸³ There are many purified lectin from different sources show the anti-insect properties, which includes; the chitin-binding lectins from rice (Oryza sativa) and stinging nettle also inhibited larva1 growth of the (Callosobruckus maculates) cowpea weevil.⁸⁴ It was found that Bauhinia monandra leaf lectin produced mortality in Zabrotes subfaciatus and Callosobruchus maculatus when incorporated into an artificial diet.⁸⁵ The seeds of leguminous plants (Amburana cearensis, Anadenanthera macrocarpa, Dioclea megacarpa, Enterolobium contortisiliquum, and Piptadenia) are promising sources of primary metabolites, especially lectins and trypsin inhibitors and secondary metabolites with larvicidal activity against A. aegypti with low toxicity to mammals.⁸⁶ The leguminous crops have also suffered greatly due to various diseases and pests for example, the plant parasitic nematodes. Control of root knot nematode would be possible using lectins.⁸⁷ The lectins from seeds of Canavalia brasiliensis, Dioclea grandiflora, D. rostrata, and Cratylia floribunda were shown to protect artificial seeds against the beetle Callosobruchus maculatus.⁸⁸ The plant lectins are the most potent agents against insect pests of variety of crops including wheat, rice, tobacco, and potatoes. The first lectin has been reported to possess insecticidal activity was haemagglutinating lectin (PHA). The presence of PHA, the haemagglutinating lectin in the seeds protects the seeds of Phaseolus vulgaris from the attack of cowpea bruchid beetle, Callosobruckus maculatus.^89-92 Maudlin and Welburn⁹³ have been demonstrated that the lectins in the gut and hemolymph of tsetse flies are function as signaling factors of maturation for African trypanosome species. Protease inhibitors, lipoxygenases, α-amylase inhibitors which can inhibit insect digestive enzymes, and carbohydrate binding lectin proteins in plants considered as a potential control mechanisms against herbivorous insects.^94,95 The lectin extracted from Arisaema helleborifolium exhibited anti-insect activity toward the second instars larvae of B. cucurbitae.⁹⁶ The emergence of Helicoverpa armigera larvae into adults inhibited by Dioscorea batatas lectin by avidly binding to larval brush border and peritrophic membrane.⁹⁷ Majumder et al.⁹⁸ demonstrated that the lectin of Arum maculatum tuber that causes Lipaphis erysimi and Aphis craccivora to succumb, by binding to the gut brush border membrane vesicle proteins. The lectin extracted from Olneya tesota to midgut glycoconjugates and microvillae of Zabrotes subfasciatus larvae.⁹⁹ Annona coriacea which is rich in lectin displayed toxicity in Anagasta kuehniella which apparently resulted from a change in the gut membrane environment and consequent disruption of digestive enzyme recycling mechanisms by binding to midgut proteins.¹⁰⁰

Antitumor activity

The proper mechanism of the antitumor effect of plant lectins is not clear, although many have been proposed, including reduction of cell division, increasing the number of macrophages, increasing the susceptibility of tumor cells to macrophage attack, serving as a bridge between tumor cells and macrophages, and improving the immuno-competence of tumor-bearing animals. Lectins are potent biomarkers that has been used in a variety of studies such as histochemical, biochemical, and functional techniques for cancer cell characterization.¹⁰¹ It has been suggested that plant lectins may have antitumor and anticarcinogenic activities that could be beneficial in cancer treatment.^102,103 Liener (1991)¹⁰⁴ first time reported that lectin shows antitumor activity is the soybean agglutinin which capable to inhibit the growth of a transplanted tumor in rats. Xia and Ng¹⁰⁵ have reported the dark red kidney bean hemagglutinin exerted an antiproliferative activity toward leukemia L1210 cells. There are some other investigation shows that lectin has excellent antitumor activity that includes Banana lectin retarded proliferation of (L1210) cells and hepatoma (HepG2) cells. Also autumn purple bean lectin inhibited the proliferation of hepatoma HepG2 cells by inducing the production of apoptotic bodies.^106,107 Some kinds of plant lectins have been identified which induce apoptosis activity in tumor cells, viz. Viscum album L. and garlic-lectin induced tumor cell apoptosis.¹⁰⁸ On the other hand, there was one kind of mushroom lectin with tumor cell apoptosis-inducing activity, isolated from the edible mushroom Kurokawa (Boletopsis leucomelas).¹⁰⁹ The fungal lectins exhibit antitumor activities, e.g., Volvariella volvacea against sarcoma cells.¹¹⁰ The lectin from Agrocybe aegerita, which exerts its effects via apoptosis induction and DNase activity.¹¹¹ The lectin from Agaricus bisporus show antiproliferation activities against human colon cancer cell line and breast cancer cell line, and Tricholoma mongolicum lectin inhibits mouse mastocytoma cells in vitro and sarcoma cells in vivo.^112,113

Toxicity of lectin

Elevated concentration of lectin in foods, such as beans, cereal grains, seeds, and nuts may be injurious to human and animals. Unfavorable possessions may restrain nutritional deficiencies, gastrointestinal distress, immune allergic reactions, and food poisoning.¹¹⁴ Lectin can be a source of leptin resistance. Such leptin resistance may decipher into diseases, particularly it could be liable for obesity in humans who have high levels of leptin.¹¹⁵ Lectin as well basis of rigorous inflammation and devastation of epithelial cells, edema, hyperemia, and hemorrhages in the lymphatic tissues are very ordinary. Lectin when injected to animals local necrosis and fatty changes can be detect in the liver tissue whereas hemorrhages are observed in the stomach, the intestinal wall, and other organs.¹¹⁶

Conclusion

Lectin is well-studied plant proteins that subsisted a significant prototype of evenness and variability of their binding regions. Lectin used in extensive relevance such as agglutination, blood typing, mitogenic stimulation, toxicity to cells, inhibition of fungal, bacterial and viral growth, insecticidal property, anti-HIV property, anti-cancer, neurosciences, and recently reported to have nuclease like activity. The high concentration of lectin causes toxicity, food poisoning, and tissue damage and leptin resistance. In this review, we focused on plant lectin, especially legume lectin, its structure, biological activity and applications. Lectin has broad spectrum of biomedical application in cancer therapy, HIV treatment, and now recently neurons study.

Glossary

Abbreviations:

RIPs

ribosome inactivating proteins

rRNA

ribosomal RNA

HIV

human immunodeficiency Virus

HTLV

Human T lymphotrafic virus

Con A

Concanavalin A

WGA

Wheat Germ agglutinin

PHA

Phytohemagglutinin-

RBC

Red blood cells

AIDS

acquired immunodeficiency syndrome

10.4161/psb.26595

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.