## 4 Discussion
Hazelnuts are also an excellent source of vitamin B (i.e., B1, B2, B6), \(\alpha\)-tocopherol niacin, thiamin, phytosterols (mainly \(\alpha\)-sitosterol and gallic acid, caffe acid, sinapic acid, and quercetin), and many other essential minerals [86; 87]. In one study, the consumption of hazelnuts reduced inflammation and increased the expression of several antioxidant enzymes without weight gain [86]. Hazelnuts augment cellular antioxidant properties and reduce levels of several inflammatory cytokines and oxidation of LDL in healthy subjects [87]. Hazelnuts can also suppress inflammation and reduce the circulatory levels of inflammatory cytokines [88]. RA is an inflammatory disorder characterized by the overproduction of inflammatory cytokines and PGs--especially type E (i.e., PGE2) [89]. PGs, including prostacyclin (PGI\({}_{2}\)), PGE\({}_{2}\), prostaglandin \({\rm F2\alpha}\) (PGF\({}_{2\alpha}\)), PGD, and TXA2 (a vasoconstrticr), are lipid products produced from the metabolism of the membrane ARA by the action of COX-2 [90]. The levels of all PGs are significantly amplified in the RA patients' synovial tissue and AIA animal model [89; 91]. All PGs are involved in different aspects of RA, and PGE2 is synthesized by the chondrocytes and synovial fibroblasts in response to inflammatory cytokines. PGE2 is among the most effective PGs in the pathogenesis of RA and amplifies the disease. The damaging effect of PGE2 is via numerous mechanisms, including the death of the hyperplasia of the synovium, limiting protection of T-cells from apoptosis, erosion of cartilage, vasodilitation, fluid extravasation, and pain [89]. However, the inhibition of COX-2 activity by non-steroidal anti-inflammatory drugs (NSAIDs) and the suppression of PGE2 signaling by blocking or deleting their receptors ameliorates the severity of RA and preventsits progression [89; 91; 92; 93]. The ratio of \(\omega\)-6/\(\omega\)-3 is a key index for the balanced synthesis of eicosanoids in the body [94]. The \(\omega\)-3 fatty acids can reduce the production of eicosanoids from ARA [95]. EPA is a substrate for the COX and LOX enzymes leading to the synthesis of alternative eicosanoids that are typically less potent than those produced from ARA [95]. In this study, all nut oils reduced PGE2 (Figure 6), suggesting two possibilities. The first suggestion is that walnut, peanut, cashew, and hazelnut oils reduce the inflammatory levels of TNF-\(\alpha\) and IL-1\(\beta\). The other possibility is that these oils suppress the activity of COX-2, thus suppressing the generation of PGE2. In addition to their high content of \(\omega\)-3 PUFAs, nuts are a good source of several antioxidants and bioactive anti-inflammatory components. Walnut's contain significant amounts of antioxidants, i.e., more than 20 mmol/100 g, followed by peanuts (2.0 mmol/100 g), hazelnuts, and cashew nuts (0.3-0.7 mmol/100 g) [96]. Similarly, another study has reported the highest content of phytosterol (which is supposed to have anti-inflammatory effects) in walnut (307 mg/100 g), followed by peanut (284 mg/100 g), cashew nut (199 mg/100 g), and hazelnut (165 mg/100 g) [97]. Therefore, other than the fatty acid profile, the synergetic interaction between antioxidants and many bioactive constituents of walnut and peanuts can be the possible cause of higher inflammation-decreasing properties in walnut and peanut oil than in other groups such as hazel nut and cashew nut.