# Can Walnut Serve as a Magic Bullet for the Management of Non-Alcoholic Fatty Liver Disease?
## 3 Results and Discussion
### Mechanisms by Which Walnut Contributes to the Management of NAFLD
#### 3.2.3 Effects of Walnut on Inflammation and Immunity Inflammation  
Walnut polyphenols have been studied for treating inflammation [5]. In addition, walnut is exceptionally rich in \(\alpha\)-linolenic acid, a plant-based omega-3 polyunsaturated fatty acids, and fibers in walnut also have anti-inflammatory properties. Walnut is also an excellent source of \(\gamma\)-tocopherol, which is a potent free radical scavenger and reduces proinflammatory eicosanoids and inflammatory responses. In a colon cancer cell line, COLO205, walnut phenolic extracts significantly inhibited IL-8 and IL-1\(\alpha\) expression and attenuated both TNF-\(\alpha\)-induced inhibitor of nuclear factor kappa B (lxB) phosphorylation/degradation and the DNA binding activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\(\kappa\)B). The oral administration of walnut phenolic extracts significantly reduced the severity of colitis in both acute and chronic colitis models [79]. In a systemic review and meta-analysis of randomized controlled trials, nut consumption improved vascular endothelial function but not C-reactive protein, the most common inflammatory maker for the evaluation of anti-inflammatory effects of food or diet [80], whereas a two-year supplementation of walnut to the diet improved the expression of six inflammatory markers, i.e., granulocyte-macrophage colony-stimulating factor (GM-CSF), INF-\(\gamma\), IL-1\(\beta\), IL-6, TNF-\(\alpha\), and sE-selectin, suggesting the long-term effects of walnut on meta-inflammation, a chronic sustained subclinical inflammation associated with obesity, diabetes mellitus and aging [81]. Collectively walnut--with its abundant anti-inflammatory components--may be effective against inflammation associated with NAFLD. ImmunityRecent evidence suggests that immunologic imbalances in the liver drive the development and progression of NAFLD. In NASH, immune cells are recruited into the liver and activation of these cells releases inflammatory molecules. Although the innate immune mechanism is considered a major contributing factor, recent evidence indicates that adaptive immunity also plays an important role in the progression of NAFLD to NASH [70]. Walnut contains many immune-potentiating components such as vitamin E, vitamin B-6, copper, zinc, and selenium. Recent studies have also suggested that walnut hydrolyzates, walnut polyphenic extracts, and walnut oligopeptide are effective immune boosters in several animal studies. In an animal study using BALB/c mice, walnut protein hydrolyzates (albumin, glutelin, and globin) improved immune indices such as splenic lymphocyte proliferation, phagocytic activity of macrophage, number of CD4\({}^{+}\) and CD8\({}^{+}\) T cells, and IgA, suggesting the use of walnut proteins as nutritional resources to boost the immune function [82]. In another animal study that employed specific pathogen-free Kunming mice [83], walnut phenolic extracts significantly attenuated immunotoxicity in splenocytes exposed to 4-pentylphenol and 3-methyl-4-nitrophenol, both of which are components of vehicle emissions that are known to be toxic to spleen, an immune organ that links innate and adaptive immunity [84]. Treatment with walnut phenolic extracts--\"containing least 16\" phenols, including ellagitannins, quercetin, and gallic acid--was shown to significantly increases in the percentages of splenic T lymphocytes (CD3+ T cells) and T cell subsets(CD4+ and CD8+ T cells), as well as the production of T cell-associated cytokines (IL-2 and IL-4,) in cells exposed to the splenotoxins. In a recent animal study using BALB/c mice [85], walnut oligopeptide significantly improved humoral- and cell-mediated immune responses, macrophage phagocytosis, and natural killer cell activity, along with T-helper cell stimulation and increased the production of cytokines and immunoglobulin. Food-derived peptides have been suggested as effective and safe immunomodulatory supplements [86], as demonstrated by their positive effects on macrophages.