**2.5 Polysaccharides**

Polycarbohydrates are another name for polysaccharides and are present in many foods. Its constituent monosaccharide units and glycosidic connections make up the long-chain polymeric carbohydrates. With the aid of amylase enzymes, it rapidly reacts with water through hydrolysis. This enzyme makes the constituent sugars i.e., monosaccharides, and oligosaccharides from polysaccharides [95]. Biologically, it is stored as starch, glycogen, galactogen, cellulose, and chitin. It is found in various plants including marine sources. Marine polysaccharides are used as medicine for variable disorders. Marine sources of polysaccharide have enriched contents of organic compounds like terpenoids, polyethers/ketides, lipo-glycoproteins, peptides, and polysaccharides [96]. It acts on various cell surface receptors altering cell proliferation and differentiation. Furthermore, it possesses immunomodulatory effects [97]. Pectin and Acemannan are also recognised as important bioactive immunomodulating substances.

The complex polysaccharide molecule known as pectin contains d-galacturonic acid monomers that have been esterified and connected by α-(1–4) chain [98]. In its typical state, pectin functions as an adsorbent and rapidly binds to various poisons, germs, and irritants in the intestinal mucosa. It lowers the pH in the intestinal lumen and has calming effects. The digestive system's alkaline environment is treated using modified pectin. Citrus pectin and modified citrus pectin, which are plant-based pectins, are known to have immunomodulatory effects by increasing the proinflammatory cytokines such as IFN-γ, IL-17, and TNF-α [99]. Pectin also inhibits the pro-inflammatory TLR2-TLR1 pathway, which is how it blocks the toll-like receptor 2 (TLR2) [100]. Specific polysaccharides produce immunomodulatory effects and influence immune cell function. Additionally, interactions between T-cells, monocytes, macrophages, and polymorphonuclear lymphocytes have altered innate and cell-mediated immunity through the influence of polymers of polysaccharides [101]. Because of this, it is utilised as an immunomodulatory medication to treat immunological diseases.

Acemannan, a mucopolysaccharide molecule, is widely distributed in aloe vera leaves. It has the chemical name β-(1,4)-acetylated soluble polymannose. It induces IFN, IL-1, TNF, and prostaglandin E2 release from activated macrophages. Additionally, it improves the control of macrophage phagocytosis, T-lymphocyte activity, and non-specific cytotoxicity. Potential anti-oxidant, antiviral, immunostimulant, antineoplastic, wound-healing, bone-proliferation, and neuroprotective effects are present [102]. It stimulates the generation of nitric oxide and macrophage-mannose receptors, which activate immune cells like macrophages [103]. Furthermore, through IFNγ-associated suppression of bcl-2 (B-cell lymphoma 2) expression, acemannan stimulates the RAW 264.7 cells [104]. Treat immunological disorders, it is regarded as an immunomodulatory agent.

## **2.6 Tannins**

Tannins are substances with a high molecular weight that are water soluble and frequently found in plants as a complex with proteins, polysaccharides, and alkaloids. Depending upon their solubility or hydrolysis product, tannins are divided into hydrolysable tannins, proanthocyanidins, phlorotannins. Gallic acid esters are used to produce hydrolysable tannins. Phlorotannins are formed from phloroglucinol, obtained from brown algae, and condensed tannins are a combination of polyhydroxy flavan-3-ol monomers. Walnuts, peaches, berries, apples, and grapes are among the significant sources of tannins [105]. Numerous preclinical studies have shown their immunomodulatory properties.

Punicalagin (PCG), an ellagitannin, has several health benefits. According to Lee et al. investigation, the immunosuppressive properties of PCG derived from Punica granatum depend on its impact on the nuclear factor of triggered T cells (NFAT). Data showed administration of PCG inhibited leukocyte response, IL-2 expression, and CD3 + T cell infiltration. Moreover there is some evidence that PCG may be a free radical scavenger and thus can be used as potent immunosuppressive drug [106]. Reddy Reddana did yet another study on chebulagic acid's (CA) immunosuppressive properties, derived from Terminalia chebula, on LPS-induced RAW 264.7 cell line. The expression of IL-2, TNFα and ROS production was considerably reduced after treatment with CA. A dose-dependent trend was also observed in the inhibition of NF-κβ activation, p38, JNK, and ERK 1/2 phosphorylation [107]. Furthermore, Corilagin extracted from T. chebula showed the neuroprotective activity by downregulating the H2O2 stimulated PC12 cells death [108].

### **2.7 Saponins**

The group of naturally occurring glycosides known as saponins is abundantly found in many different parts of plants, including leaves, flowers, shoots, roots, tubers, and seeds [109]. These are complicated compounds with a non-sugar (aglycone) component joined to a sugar moiety. Saponins fall into one of two groups based on their aglycone skeleton. Triterpens saponins, most of which are found in dicotyledonous angiosperms, make up the first class. Steroid saponins, which are primarily found in monotyledonous angiosperms, are found in the second class. Most of the oligosaccharides that make up the glycone portion of saponins are connected to the hydroxyl group by an acetal linkage. Numerous in vivo and in vitro investigations, have shown that plant-derived saponins can increase the immunogenicity of several vaccines. One of the most well-known functions of saponins is their usage as immunoadjuvants, which modulate the immune system produced by cells and aid in creating antibodies [109, 110]. Different saponin chemicals can stop the cell cycle, induce apoptosis and inhibit cancer cells. On rat liver microsomes, Ablise et al. examined the immunotherapeutic effect of glycyrrhizin produced from Glycyrrhiza glabra. With 1.0 mg/mL of glycyrrhizin, the classical complement pathway was significantly inhibited, and the antioxidant activity was increased. Another study by Punturee et al. found that utilising peripheral blood mononuclear cells (PBMCs) to extract Asiaticoside saponin from Centella asiatica had positive results and the data showed that as compared to the non-treated group, asiaticoside administration at 100 mg/kg significantly increased phagocytic index and total WBC count [111]. The immunological responses, both cellular and humoral, are also improved.

## **2.8 Sterols and sterolins**

Combining sterols and sterolins improves NK cells' capacity to kill the NK 562 target cell line. Additionally, it has been proposed that specific ratios of sterols could restore the delicate balance between Th1 and Th2 cells, which decides how the immune response would turn out. At low concentrations, the phytosterols -Sitosterol and its glycoside more than doubled the in vitro proliferative response of T-cells

#### *Perspective Chapter: Phytocompounds as Immunomodulators DOI: http://dx.doi.org/10.5772/intechopen.108858*

triggered by sub-optimal amounts of phytohaemagglutinin. Moreover, it has been suggested that sterols and sterolins can control the amounts of Th1 and Th2 mediated cytokines, aiding in enhancing immune responses. Potent immunomodulators, phytosterols, β-Sitosterol, and its glycoside can enhance the proliferative responses of T cells even at low concentrations [112].

Rasool et al. used albino Wistar strain rats to study the immunomodulatory activities of withanolide derived from Withania somnifera. Withanolide administration in the rats dramatically reduced the proliferation of lymphocytes triggered by mitogens, the traditional complement pathway, and hypersensitive reactions. Withanolide might thus be developed into a potent immunosuppressive drug, according to the study [113]. Furthermore, by enhancing the Th1 and Th2 immune responses in mice with disseminated candidiasis, β-sitosterol and daucosterol also demonstrated immunomodulatory action [114]. The immunomodulatory properties of phytosterols isolated from Clinacanthus nutans by employing murine cells were described in another investigation by Lee and colleagues. To evaluate the immunosuppressive effects of phytosterols (stigmasterol, shaftoside, and β-sitosterol), mitogen-induced B and T-cell proliferation and the production of helper T-cell cytokines were observed. The results showed that treatment with phytosterols dramatically reduced T-cell proliferation and enhanced the production of Th1 and Th2 mediated cytokines [115].

The summary of phytocompounds and their mechanism of immunomodulation are expressed in **Tables 1**–**3**.


#### **Table 1.**

*Immunomodulatory actions of flavanoids and coumarins.*


#### **Table 2.**

*Immunomodulatory actions of alkaloids and terpenoids.*



#### **Table 3.**

*Immunomodulatory actions of tannins, glycosides and saponins.*
