**2.1 Polyphenol**

Any compound, including functional derivatives (esters, glycosides, etc.), with an aromatic ring and one or more hydroxyl substituents is referred to as a "polyphenol" or "phenolic". Polyphenols in foods or natural health products come from one of the main classes of secondary plant metabolites derived from tyrosine or phenylalanine. They are widely found in fruits, vegetables, beverages and cereals [27].

### *2.1.1 Stilbene derivatives*

The phenolic compounds known as stilbenes have two aromatic rings connected by an ethene bridge (C6–C2–C6) [28]. Trans-3,5,4<sup>0</sup> -trihydroxystilbene, also known as resveratrol, is a well-known phytoalexin of the stilbene class. It is a natural substance found in grapes, berries, and other traditional Chinese medicines like Polygonum cuspidatum. It is known to work by modulating a various distinct pathways to produce its effects [29]. Numerous cell-signalling molecules connected to inflammation have been demonstrated to bind to resveratrol. It inhibits cyclooxygenase-2 (COX-2) protein expression in mammary epithelial cells and activates phorbol-12-myristate-13 acetate (PMA) to control the protein kinase C (PKC) transduction pathway for immunomodulatory effects [30]. Additionally, it inhibits p65 subunit phosphorylation, IκBα kinase phosphorylation, and NF-κB for DNA activities, all of which are implicated in immunological actions [31, 32]. Moreover, it blocks the activator protein-1 (AP-1) that is in charge of immunological effects [33]. Experimental evidence suggests that resveratrol blocks the lipopolysaccharide (LPS) induced NF-κB p65 nuclear translocation, as well as the down-regulation of IL-6, nitric oxide, IL-18, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP-2 and MMP-9) secretion in E11 cells. Furthermore, it inhibits THP-1 and U937 monocyte migration in inflammatory areas by immunological reactions [34]. Resveratrol dramatically decreases the expression and activity of inducible nitric oxide synthase (iNOS) [35].

#### *2.1.2 Hydroxycinnamic acids*

Another name for hydroxycinnamic acids is hydroxycinnamates (i.e., curcumin, and p-Coumaric acid). Chemically, it belongs to the phenylpropanoids or class of aromatic acids. It is a hydroxy derivative of cinnamic acid, and has a C6-C3 skeleton. It appears as α-Cyano-4-hydroxycinnamic acid in food, including fruits, vegetables, and cereals, and has the potential to scavenge free radicals and guard against inflammation, dyslipidemia, insulin resistance, diabetes, and cardiovascular illnesses [36]. The molecular function of hydroxycinnamic acids is to improve the host immune response and lessen harm to the body's essential organs [37]. The active component of Curcuma longa is curcumin, a hydroxycinnamic acid derivative and is known as diferuloylmethane chemically [38]. The anti-platelet, anti-inflammatory,

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

hepatoprotective, anti-cancer, and anti-arthritic properties of curcumin make it a popular treatment option in Ayurvedic medicine [39]. It is also recognised to have immunomodulatory effects. Experimental evidence suggests that it inhibits the transcription factors such as cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding protein (C/EBP), CTCF, β-catenin, heat shock factor-1, Notch-1, hypoxia-inducible factor-1 (HIF-1), early growth response-1 (Egr-1), AP-1, signal transducers and activators of transcription (STAT)-1, 3, 4, 5 and NF-κB [40]. Additionally, AP-1 and NF-κB, which are immune cell transcription factors, are suppressed by curcumin to provide the anti-tumour effect [41].

## *2.1.3 Flavonoids*

Flavonoids are one of the most prevalent naturally occurring substances in all vascular plants. At least 6500 naturally occurring flavonoids have been discovered, and nearly all plant tissues are capable of producing flavonoids. The 15 carbon atoms that make up the essential backbone of flavonoids (C6-C3-C6) define them. They are typically divided into seven classes based on their chemical makeup: flavones, flavanones, flavonols, flavanonols, isoflavones, flavanols, and anthocyanidins [42]. They often take the form of a flavonoid glycoside or an aglycone. While aglycones are primarily found in woody tissues, flavonoid glycosides are primarily found in leaves, flowers, or fruits. Both flavonoid aglycones and glycosides can be found in seeds. Flavonoids have long been known to have anti-inflammatory, anti-hepatotoxic, antiatherogenic, anti-osteoporotic, anti-allergic, and anti-cancer properties, in addition to their well-known antioxidant activity [43]. Quercetin is a flavonol that is present in foods including grapes, tea, onions, apples, and leafy green vegetables [44]. The most well-known active ingredient in tea is epigallocatechin gallate (EGCG), a potent antioxidant. It can affect phase I and phase II enzymes in addition to being a potent anti-inflammatory and antioxidant that guards the body against the damaging effects of free radicals [45]. The inhibition of transcriptional factors (such as NF-kB and AP-1) and the elevation of Nrf-2, which results in a decrease in pro-inflammatory mediators, are thought to be the anti-inflammatory modes of action of quercetin and EGCG [46]. These properties have led researchers to consider using these chemicals to treat inflammatory illnesses, ageing, neurological disorders, inflammatory bowel diseases, cancer, and diabetes.
