**2.3 Psoriasis**

*Apolipoproteins, Triglycerides and Cholesterol*

pathway [27].

**2.2 Irritable bowel disease (IBD)**

natural agonists in resolution of pulmonary inflammation. Briefly, lipoxins are arachidonic acid derivatives generated via multistep enzymatic reactions mediated by lipoxygenases to produce trihydroxy-tetraene-containing eicosanoids. On the other hand, resolvins are endogenous autacoids, derived from EPA and DHA as E-series (RvE) and D-series (RvD) resolvins, respectively. The intracellular signaling pathways resolvins adopt to bring about their actions, involve NF-Ƙβ and kinases. Resolvins can control the NF-Ƙβ signaling pathway, for e.g. RvE1 is an agonist in the signal transduction mechanism to inhibit TNF-α induced activation of NF-Ƙβ in a concentration-dependent manner. It can also suppress pro-inflammatory LTB4-mediated BLT1 signaling by lowering activation of NF-Ƙβ. The mechanism of NF-Ƙβ repression is relevant for resolution of inflammation in pulmonary diseases, as it induces granulocyte apoptosis. With respect to kinases, the pro-inflammatory reactions involved in chronic inflammatory lung diseases, are mainly regulated by phosphatidylinositol 3-kinase (PI3-K) and the MAPK family member extracellular signal regulated kinase (ERK). *In vitro*, RvE1 increases phosphorylation of kinases, which has a protective effect of controlling apoptotic programs in cells. RvE1 also mitigates attenuates inflammatory pain by indirectly inhibiting the ERK signaling

Inflammatory/irritable bowel disease is a broader term used to describe the disorders that involve the inflammation of the gastrointestinal tract. Crohn's disease (CD) and ulcerative colitis (UC) are both related to IBD and result from interactions between gene, environment, and gut microbiota. Crohn's disease is characterized by chronic inflammation which relapses and remits, ultimately affecting the entire gastrointestinal tract, whereas ulcerative colitis inflammation is mostly confined to the colon-rectum junction. The pathogenesis of the disease mostly involves predisposing genetic, environmental, and immunologic factors [28, 29]. More than 200 gene regions have been identified that confer risk for Crohn's disease or ulcerative colitis in the European population [30]. The currently available drugs to treat IBD work by targeting receptors of T-cell activation (e.g., visilizumab, abatacept), prebiotics, probiotics targeting the intestinal flora antibiotics, adhesion molecule blockers (e.g., MLN-02, alicaforsen, natalizumab), cytokines (e.g., interleukin 10) [31]. Despite the advent of new therapeutic agents in recent years, current treatments are modestly successful with notable side effects [32]. Also, epidemiologic studies reported that increased animal fat/n-6 PUFA intake with the prevalence of both CD [33, 34] and UC [35]. Hence it is necessary to understand the role of n-3 PUFA and its metabolites in disease prevention of IBD. The potential role of n-3 PUFA in inflammation has garnered interest in fatty acid profiling in various metabolic and inflammatory diseases. Like other diseases, the inflammatory state in IBD is a result of the eicosanoid pathway with elevated levels of LTB4, LTC4, and thromboxanes (A1 and A2) in the inflamed intestinal mucosa [4]. Many clinical studies conducted with fish oil or EPA supplementation reported the inhibitory effect on inflammatory molecules production [36–38]. Animal model studies are in line with results of clinical studies concluded that n-3 PUFA ameliorated the intestinal inflammation [39–41]. The immunomodulatory and anti-inflammatory effects of n-3 PUFA are reported either directly [42, 43] or indirectly by the generation of PUFA metabolites containing hydroxyl groups i.e. resolvins, hydroxy fatty acids etc. [44]. Although there is a reasonable amount of data available on anti-inflammatory effect of n-3 PUFA, limited reports available in their use on IBD patients; hence deeper research in the aspects of dose, and mechanistic understanding is needed to replace or enhance the effect of

currently available drugs along with nutritional intervention.

**200**

Psoriasis is an inflammatory skin disease, affecting about 2% of the general population, characterized by hyperproliferation and poor differentiation of keratinocytes, increased vascularization of the skin, leukocyte infiltration and fibroblast activation [45]. It is a skin disease considered to be resulting from T-cell-mediated inflammation, wherein the inflammatory reaction is controlled by diet, lifestyle, and environmental cues such as infections and stress. Although the etiology remains unknown, accumulating evidence indicates that cytokines, mainly tumor necrosis factor α (TNF-α), IL-17 and IL-23, play essential roles in the development [6]. In the psoriatic lesions, inflammatory dermal dendritic cells (DCs) produce IL-23 that enhances the production of T cytotoxic 17 cells (Tc17) or IL-17 from T helper 17 cells (Th17) in the skin, leading to epithelial hyperplasia and inflammatory cell infiltration [46]. A documented and conclusive cure for psoriasis does not exist, some of the commonly used treatments to reduce the severity of disease and lessen the impact are phototherapy, topical and systemic therapies in moderate-tosevere psoriasis and drugs are corticosteroids, methotrexate, tar, cyclosporine, and emollients. Nevertheless, almost all the mentioned treatments are accompanied by major adverse effects [47]. Among nutritional components regulating the pathophysiology of psoriasis, PUFAs proved to be promising in the treatment of many skin diseases as safe, including psoriasis [48]. Calorie restriction or weight loss may also influence the severity of the disease. However randomized control trial study conducted by Guida et al. concluded that calorie restriction (20 kcal/kg/day) along with n-3 PUFA (2.6 g/day) enriched diet improved the clinical response of immunemodulating drugs in obese psoriatic patients [49]. Many clinical studies have demonstrated that the administration of fish oil or n-3 PUFA ethyl esters in psoriatic animal model/patients ameliorated the degree of skin inflammation [ 44–48, 50]. However, the reports on the exact mechanism are limited. A recent study conducted by Sawada et al. using metabolite produced by n-3 PUFA such as resolvinE1 (RvE1) in imiquimod (IMQ )-induced murine psoriasis mouse model concluded that RvE1 remarkably suppressed the epidermal hyperplasia and inflammatory cell infiltration in the psoriatic skin. These suppressive effects are due to the antagonistic effect of RvE1 on BLT1 production, a receptor of LTB4 and decrease in mRNA expression of cytokines (IL-17 and IL-23) indicating the novel mechanism of psoriatic pathogenesis and potential of RvE1 as an adjuvant in the psoriatic therapy [51].
