## 2 Pomergnate Health-Promoting Properties
### Anti-Inflammatory Properties  
Inflammation represents the first physiological response against injuries caused by physical agents, poisons, and others. [5, 77, 78, 79]. The defense system, the so-called primary inflammation, neutralizes infectious microorganisms, removes irritation, and maintains ordinary physiological functions [80]. The phlogosis is triggered by various chemical and biological agents, including pro-inflammatory enzymes and cytokines, such as eicosanoids or degradation products of inflamed tissue. According to recent reports, pomegranate exhibited potential as an anti-inflammatory medicine in both in vitro and in vivo studies. Some extracts of pomegranate, especially the cold-pressed seed extract, decrease the action of cyclooxygenase and lipoxygenase enzymes in vitro. Cyclooxygenases are useful enzymes for the degradation of arachidonic acid into prostaglandandins, key mediators of inflammation. Lipoxygenase, on the other hand, mediates the transformation of arachidonic acid into leukotrienes and it is reduced by extracts of pomegranate seeds [81, 82]. [PERSON] et al. [83] report that punicic acid (12), a fatty acid contained in pomegranate seed oil, has an anti-inflammatory activity due to the inhibition of neutrophil activation, and therefore limits lipid peroxidation. [PERSON] et al. [80] analyzed some hydrolyzable tannins, including punicalagin (9) and punicalin (13), isolated from pomegranate by fractionation. Following in vitro studies, each of these compounds exerted a dose-dependent inhibitory effect on nitric oxide synthesis with an important anti-inflammatory effect [84]. [PERSON] et al. [85] have shown that the dietary inclusion of pomegranate fruit extract caused an important reduction in expression of the markers of vascular inflammation, thrombopondin, and cytokine transforming growth factor (TGF-\(\beta\)1) in obese Zucker rats, a model of metabolic syndrome. [PERSON] et al. [86] indicated that pomegranate composition could prevent colon inflammation before and during the disease process. They assessed the consequences of pomegranate intake and its main microbiota-derived metabolite urothel-A (UROA) on colon inflammation. Results suggested that URO-A could represent the most powerful anti-inflammatory compound derived from pomegranate ingestion in healthy subjects, whereas in colon inflammation, the effects could be caused by the nonmetabolized ellagitannin-related fraction. Additionally, pomegranate extract supplementation has been shown to lead to decreased levels of prostaglandin E2 in the colon mucosa due to reduced cyclooxygenase-2 (COX-2) overexpression and diminished levels of prostaglandin synthetase E (PTGES) due to high ellagic acid (8) content [87]. [PERSON] et al. analyzed the effects of pomegranate peel extract (PPE) on THP-1 monocytic cells exposed to PM10, air-borne particulate matter with a diameter of \(<\)10 \(\upmu\)M (PM10) that are known to induce cytotoxicity and ROS production and also to increase the expression and secretion of inflammatory cytokines, such as TNF-\(\upalpha\), IL-1\(\beta\). This study demonstrated that PPE at 10-100 \(\upmu\)gmL\({}^{-1}\) is able to lower the production of ROS and the expression of TNF-\(\upalpha\), IL-1\(\beta\), MCP-1, and ICAM-1 thus preventing inflammatory events due to particulate matter [88]. A recent study by [PERSON] et al. explore the inflammation effects of pomegranate flower (PFE) ethanol extract in lipopolysaccharideacharide (LPS) -induced RAW264.7 cells. LPS is a component of the Gram-negative bacteria cell wall that has been often used in inflammatory response because it can activate macrophages. Their findings suggest that PFE is able to suppress the production of NO, PGE-2, and pro-inflammatory cytokines (TNF-\(\upalpha\), IL-6, IL-1\(\beta\)), as well as the protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 macrophages.