Immunomodulatory polysaccharides

Immunomodulatory polysaccharides activate macrophages in the host immune system and generate cytokines (e.g., ILs, TNF, and NK) that are important part of defense in the immunosurveillance system [1-4,135]. In addition, these cytokines display antitumor property and help to eliminate the existing tumor [4,5,85]. 

A number of important publications appeared in the literature on immunomodulatory polysaccharides [1-5,85,140]. For example, Grifolan, which is... 

The above-mentioned findings are further supported by recent research that demonstrated that lyceum has antioxidant, neuroprotective (retinal ganglia and brain cells), cytoprotective, hepatoprotective (extract, glycolipids, pyrroles, and physa-lien), immunomodulatory (polysaccharides) and anticancer activities in various animal models. ... 

G115 extract protects mice from viral infection G115 extract exerts immunomodulatory effect in mice (NK, Interferon) Polysaccharides stimulates the immune function in mice and guinea pig (antibodies, phygocytosie, complement, B/T cell ratio)... 

Nephritis is an autoimmune disease caused by activation of the complement system. Cinnamon cortex and cinnamon oil inhibited complement formation in vitro. Cinncassiol C, and its glucoside, the cinncassiols C2 and C3 and cinncassiol D, and its glucoside were reported to possess anticomplementary activity. A water-soluble polysaccharide isolated from the cinnamon extract showed complement system activity (Tang and Eisenbrand, 1992). 2-Hydroxycinnamaldehyde and 2-benzyloxy cinnamaldehyde isolated from the stem bark of cinnamon possessed immunomodulatory effects (Koh et al., 1999). 

In assays to assess the immunomodulatory activity of a polysaccharide isolated from white mulberry root bark, the compound was found to enhance proliferation of splenic lymphocytes in a synergistic manner in the presence of mitogens. However, the compound suppressed primary IgM antibody production from B cells, which was activated with lipopolysaccharide, a polyclonal activator, or immunized with a T-cell-dependent antigen, sheep red blood cells (Kim et al. 2000). 

Large quantities of polysaccharides are available in nature and many of them display a variety of biological functions [1 ]. There is an abundance of literature on the isolation of bioactive polysaccharides from botanical sources [1-5]. This area of research has attracted a lot of interest due to the fact that most of the bioactive polysaccharides are nontoxic with minimal side effects [4,5]. Hence, this class of biopolymers forms ideal candidates for therapeutic applications. Some of the notable bioactivities of botanical polysaccharides include antioxidant, immunomodulatory, and antitumor properties [4-10]. However, the mechanism of action of these biopolymers is not well understood. In general, one of the primary mechanisms of action of polysaccharides is nonspecific immunomodulation [8]. The key mechanism behind the immunomodulatory, anticancer, antibacterial, and other pharmacological activities of plant polysaccharides is to activate macrophages, which then leads to modulation of the complement system that activates the cells involved in innate immunity and improves host defense [1—4,11,12]. 

Therefore, the well-established concept of inununoediting demonstrates that the weak immune system of the host is one of the key factors responsible for the formation of cancer. Hence, keeping the inunune system healthy is the best way to initiate timely productimi of appropriate chemokines and cytokines that recognize and destroy cancer cells [55]. In this context, immunomodulatory plant/mushroom polysaccharides have immense importance for the prevention and cure of cancer. 

One of the primary mechanisms of action of polysaccharides is nonspecific immunomodulation that leads to the production of cytokines [4,8]. The key mechanism behind the immunomodulatory, anticancer, antibacterial, and other pharmacological activities of plant polysaccharides is to activate macrophages, which then leads to the modulation of the complement system that activates the cells involved in innate immunity and improves host defense [1, 11,12]. 

As discussed in sections Introduction and Molecular Basis of Cancer Formation and Development, the formation of cancer is very complex. Generally, the cyclic processes involving oxidation and inflammatory processes (Figs. 1 and 2) lead to the formation of cancer cells. These cancer cells survive if the host is immunocompromised which is generally the case under the conditions of severe oxidative stress [55,58,60]. This leads to the cancer cell proliferation and tumor formation [29]. Finally, due to immune exhaustion, the cancer growth overpowers immune response. Therefore, oxidative stress is the main cause of cancer formation and the subsequent immune exhaustion is the source of cancer growth. Hence, the chemotherapeutics for the treatment of cancer need to be efficient immunomodulators and antioxidants. It is important to note here that the plant polysaccharides with immunomodulatory properties concurrently possess antioxidant activity [5,85] and hence are the ideal candidates for the prevention and treatment of cancer. 

The first line of screening programs aims to discover the plant polysaccharides that possess immunomodulatory, antioxidant, and antitumor properties. 

It may be emphasized again here that the botanical polysaccharides with immunomodulatory properties are also known to be potent antioxidants [5,27]. Many studies have shown that the oxidative stress producing free radicals lead to both initiation and promotion of multistage carcinogenesis [25,35]. These findings suggest that the plant polysaccharides, which are natural antioxidants, immunomodulators as well as antitumor agents, are expected to be the future chemotherapeutics of choice. 

POLYSACCHARIDES FROM PLANTS AND MUSHROOMS WITH IMMUNOMODULATORY AND ANTICANCER ACTIVITIES... 

As discussed in the previous sections, there is an abundance of literature on anticancer and immunomodulatory activities of polysaccharides isolated from medicinal plants and mushrooms. Some of the bioactive polysaccharides that have been identified in the recent years are summarized in Table 2 along with... 

TABLE 2 Anticancer and Immunomodulatory Activities of Polysaccharides Isolated from Medicinal Plants and Mushrooms ... 

Many polysaccharides, especially 5-(1 3)-glucans, have been shown to have immunomodulatory effects by cytokine-stimulating activities. Cytokines can increase proliferation and differentiation of macrophages, T and B cells, and enhance cellular mechanisms of antitumour activity and antibody production. The polysaccharides are sometimes linked to a protein peptide. The so-called D-fraction ,... 

Shi M,Yang Y, Hu X, Zhang Z. Effect of ultrasonic extraction conditions on antioxidative and immunomodulatory activities of a Ganoderma lucidum polysaccharide originated from fermented soybean curd residue. Food Chem 2014 155 50-6. 

Chen, X. M., Nie, W. X, Yu, G.Q., et al. 2012a. Antitumor and immunomodulatory activity of polysaccharides from Sargassum fusiforme. Food Chem. Toxicol. 50 695-700. 

Da, and an acidic arabinogalactan, MW 75,000 Da, have been isolated [122-124]. The structure of these polysaccharides differs from those of the aerial parts, since cells in suspension culture possess exclusively primary cell wall components [125]. Detailed structural data on the immunomodulatory active polysaccharides from Echinacea are presented in the chapters by Wagner et al. [150] and Emmendorffer et al. in this volume [151]. 

Immunomodulatory active polysaccharides have been isolated from the aerial parts of . purpurea [118, 123]. Their pharmacological activity is well documented and will be reviewed in the chapters by Wagner et al. and Emmendorffer et al. in this volume [150, 151]. Lectins from Echinacea purpurea have been shown to possess agglutinative properties and it is argued that they may also have adaptogenic effects [86]. 

Emmendorffer AC, Wagner H, Lohmann-Matthes ML (1998) Immunologically active polysaccharides from Echinacea purpurea plant and cell cultures. In H Wagner (ed) Immunomodulatory agents from plants. Birkhauser Verlag, Basel, 89-104... 

Three species of Echinacea are in medicinal use Echinacea ( .) purpurea E. angustifolia and . pallida. Depending on the species, the part of the plant (roots, herb) and the method of extraction (hydrophilic, lipophilic), the commercially available preparations of Echinacea contain varying concentrations of flavonoids, essential oils, polysaccharides, derivates of caffeic acid, polyacetylenes, alkylamides and alkaloids. Apart from a very few exceptions these preparations are not standardized in their content of any of these substances. The evidence available so far indicates that it is not a single component but the mixture of various groups of substances which is responsible for the observed immunomodulatory effects [5]. 

The polysaccharide isolated from B. kummingense showed an immunomodulatory action on the proliferative response of mouse splenocytes to mitogens as measured by H-thymidine incoporation [24]. 

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