Table 1.
Effect of walnut ingredients on inflammatory responses of neuronal and peripheral immune cells.
| Types of Active Ingredient | Model | Dose | Results | Ref. | |
|---|---|---|---|---|---|
| Fatty acids | Linoleic acid | Aβ25−35-treated PC12 cells | 10, 50 or 100 μM | Decreased the Aβ25-35-elevated TNF-α and IL-1β levels by 50%; inhibited increased NO production by reducing iNOS; inhibited PGE2 by decreasing COX-2; decreased the level of p-p65 and p-IκB. | [43] |
| Linoleic acid trans-10, cis-12 CLA cis-9, trans-11 CLA |
Human macrophages | 20 or 40 μM | Reduced PGE2 concentration by 23%; reduced COX-2 activity. Reduced PGE2 concentration by 39%; reduced the quantity of the active p65 NF-κB subunit by 55%. Reduced PGE2 concentration by 32%; reduced the quantity of the active p65 NF-κB subunit by 58%. |
[49] | |
| Alpha-linolenic acid | LPS-stimulated RAW 264.7 cells | 5, 10, 20 or 40 μg/mL | Inhibited translocation of the NF-κB subunit; downregulated inflammatory iNOS, COX-2, and TNF-α gene expression in a dose-dependent manner. |
[52] | |
| LPS-stimulated RAW 264.7 cells | 50 μM | Decreased expression levels of TNF-α and IL-6; increased the secretion of the anti-inflammatory cytokines IL-10. |
[53] | ||
| Carrageenan-induced hind paw edema in SD rats LPS-stimulated RAW 264.7 cells |
5 or 10 mg/kg | Reduced rat paw edema; inhibited the accumulation of nitrite and PGE2. Inhibited the protein and mRNA expression levels of iNOS and COX-2 enzymes in a dose-dependent manner. |
[54] | ||
| Phenolic acids | Ellagic acid | Arsenic-treated rats | 10–20 mg/kg by mouth, in drinking water for 8–11 days | Decreased levels of mRNA and proteins TNF-α, IL-1β, and INF-γ in the hippocampus. | [61] |
| LPS-elicited DA neuronal loss in SD rats LPS-stimulated BV-2 cells |
50 mg/kg (oral) 1 μM |
Suppressed LPS-induced activation of NLRP3 inflammasome signaling and IL-1β, TNF-α, and IL-18 protein expressions in the rat brain. Inhibited LPS-induced activation of microglial NLRP3 inflammasome signaling; eliminated production of TNF-α, IL-1β, and IL-18 in the culture medium. |
[62] | ||
| Macrophage migration inhibitory factor (MIF)-treated human peripheral blood mononuclear cells | 50 μM | Inhibited MIF-mediated nuclear translocation of NF-κB. | [107] | ||
| LPS-stimulated RAW 264.7 cells | 6.25 μM 25 μM |
Inhibited LPS-stimulated TNF-α. Inhibited LPS-stimulated IL-6 and PGE2 production. |
[65] | ||
| Gallic acid | LPS-stimulated RAW 264.7 cells | 6.25 μM | Inhibited LPS-stimulated PGE2 production. | [65] | |
| MOG 35-55-immunized C57BL/6 mice | 2 mg/day for 10 days, injected intraperitoneally | Reduced infiltration of CD4+CD45+T cells and monocytes into the central nervous system. | [66] | ||
| Phorbol 12-myristate 13-acetate (PMA) + calcium ionophore A23187-stimulated human mast cells (HMC-1) | 1–10 µM for 2–4 h | Inhibited TNF-α and IL-6 gene expression, degradation of IκBα, and nuclear translocation of p65 NF-κB induced by PMA with A23187. | [108] | ||
| Chlorogenic acid | LPS-stimulated RAW 264.7 cells | 2–20 µM for 24 h | Attenuated NO, IL-1β, TNF-α, IL-6, cyclooxygenase-2, and NF-κB expression. | [70] | |
| Mongolian gerbil model of transient forebrain ischemia | 30 mg/kg | Attenuated IL-2 and IL-4 protein expressions in pyramidal neurons. | [69] | ||
| Flavonoids | EGCG | Isolated peripheral blood mononuclear cells and CD8+T cells | 25–100 µM | Inhibited infiltration of CD8+T cells into the sites of inflammation. | [75] |
| Autoimmune thyroiditis rat model | 0.5 mg/kg, three times at a 1 h interval for 3 h, injected intraperitoneally | Reduced IL-1β, INF-γ, and TNF-α levels in thyroid tissue through suppression of the NF-κB pathway. | [76] | ||
| Rat model of cerebral ischemia/reperfusion injury |
50 mg/kg, intraperitoneal injection | Inhibited cerebral ischemia/reperfusion injury by ameliorating inflammation-related molecules TNF-α, IL-1β, IL-6, NF-κB/p65, COX-2, and iNOS in the cerebellum. | [109] | ||
| Quercetin | Human mast cells HMC-1 | 10 μM | Inhibited mast cell tryptase and IL-6 release. | [80] | |
| LPS-stimulated U937 macrophages | 30 μM | Reduced the levels of TNF-α, IL-6, and IL-1. | [81] | ||
| LPS-stimulated RAW 264.7 cells | 12.5 μM | Inhibited LPS-stimulated IL-6 and PGE2 production. | [65] | ||
| Peptides | Hydrolysate (<3 kDa) Viscozyme L + pancreatin |
LPS-treated mice | 666 mg/kg for 21 days |
Reduced NO content, normalized the overproduction of IL-6, IL-1β, and TNF-α in the brain. | [21] |
| Hydrolysate | Aβ25−35-injected mice | 400 or 800 mg/kg for 5 weeks |
Decreased the levels of NO, iNOS, NF-κB p65, TNF-α, IL-1β, and IL-6 in the hippocampus. | [24] | |
| Hydrolysate (<1 kDa) pepsin + pancreatin |
D-gal + AlCl3-treated mice | 1 g/kg for 90 days |
Suppressed the expression of TNF-α and IL-1β in the hippocampus. | [27] | |
| LPF | LPS-stimulated RAW264.7 cells | 250, 500, or 1000 μg/mL for 24 h or 48 h | Suppressed the mRNA expression of iNOS, COX-2, and TNF-α. | [36] | |
| LPF, GVYY, APTLW | LPS-stimulated BV-2 cells | 0.10 mM | Inhibited the overproduction of proinflammatory mediators (NO and PGE2); reduced the expression level of TNF-α,IL-1β, and IL-6. | [21] | |
| WEKPPVSH | LPS-stimulated BV-2 cells | 25 or 50 mM | Mitigated the secretion of TNF-α, IL-1β, and IL-6; downregulated the expression of iNOS, COX-2, and p-IkB/IkB. |
[84] | |
| EVSGPGLSPN | H2O2-treated PC12 cells | 100 μM | Suppressed the expression of IKKβ and p65 to inhibit NF-κB pathway activation; attenuated the neurotoxic cascade by overexpression of IL-1β and TNF-α. | [39] | |
Aβ, amyloid β; TNF-α, tumor necrosis factor-α; IL, interleukin; iNOS, inducible nitric oxide synthase; PGE2, prostaglandin E2; COX-2, cyclooxygenase-2; p-p65, phosphorylated nuclear factor of kappa B; p-IκB, B-cell inhibitor; CLA, conjugated linoleic acid; NF-κB, nuclear factor-κB; LPS, lipopolysaccharide; INF-γ, interferon-γ; NLRP3, nucleotide-binding domain-like receptor protein 3; MIF, migration inhibitory factor; PMA, phorbol 12-myristate 13-acetate; HMC-1, human mast cells; EGCG, epigallocatechin 3-gallate; LPF, leucine–proline–phenylalanine.