Immune Modulatory Activities of Arginyl-Fructose (AF) and AF-Enriched Natural Products in In-Vitro and In-Vivo Animal Models

Abstract

The immune system plays an important role in maintaining body homeostasis. Recent studies on the immune-enhancing effects of ginseng saponins have revealed more diverse mechanisms of action. Maillard reaction that occurs during the manufacturing processes of red ginseng produces a large amount of Amadori rearrangement compounds (ARCs), such as arginyl-fructose (AF). The antioxidant and anti-hyperglycemic effects of AF have been reported. However, the possible immune enhancing effects of non-saponin ginseng compounds, such as AF, have not been investigated. In this study the effects of AF and AF-enriched natural product (Ginofos, GF) on proliferation of normal mouse splenocytes were evaluated in vitro and male BALB/c mice models. The proliferation of splenocytes treated with mitogens (concanavalin A, lipopolysaccharide) were further increased by addition of AF (p < 0.01) or GF (p < 0.01), in a dose dependent manner. After the 10 days of oral administration of compounds, changes in weights of spleen and thymus, serum immunoglobulin, and expression of cytokines were measured as biomarkers of immune-enhancing potential in male BALB/c mice model. The AF or GF treated groups had higher weights of the thymus (0.94 ± 0.25 and 0.86 ± 0.18, p < 0.05, respectively) than that of cyclophosphamide treated group (0.59 ± 0.18). This result indicates that AF or AF-enriched extract (GF) increased humoral immunity against CY-induced immunosuppression. In addition, immunoglobulin contents and expression of cytokines including IgM (p < 0.01), IgG (p < 0.05), IL-2 (p < 0.01), IL-4 (p < 0.01), IL-6 (p < 0.01), and IFN-γ (p < 0.05) were also significantly increased by supplementation of AF or GF. These results indicate that AF has immune enhancing effects by activation of adaptive immunity via increase of expression of immunoglobulins and cytokines such as IgM, IgG, IL-2, IL-4, IL-6 and thereby proliferating the weight of thymus. Our findings provide a pharmacological rationale for AF-enriched natural products such as ginseng and red ginseng that can possibly have immune-enhancement potential and should be further evaluated.

Structural characterization of a new amino acid derivatives, Maillard Reaction product of red ginseng and potential protective activity against cisplatin-evoked intestinal injury

“…In addition, previous studies have reported that AFG has a protective effect on cisplatin-induced kidney injury through anti-oxidant stress, anti-in ammatory and anti-apoptosis pathway (Li, Zhang, 2019). Simultaneously, AF and AFG in red ginseng also have a variety of nutritional value and pharmacological effects such as immune modulatory activities , Yu et al, 2021, anti-hyperglycemic (Ha et al, 2011), anti-diabetes and its complications (Liu et al, 2020a) and antioxidant properties (Ide et al, 1999) in vitro and in vivo. With the increasing recognition of the various therapeutic effects of MRPs, amino acid derivatives as a major non-saponin health food or alternative medicine needs to be thoroughly evaluated.…”

Arginyl-fructosyl-glucose, a major Maillard reaction product of red ginseng mitigates cisplatin-evoked intestinal toxicityin vivoandin vitro

“…With the increasing recognition of the various therapeutic effects of MRPs, AF and AFG as major nonsaponin health foods or alternative medicine need to be thoroughly evaluated. 22,27 In particular, at present there is no report on the toxicity of AFG to the healthy tissues of mice and the significance of RG intake as a dietary source of AFG for intestinal protective activity remains unclear.…”

“…During steaming and drying, the abundant amino acids and reducing sugars components of RG undergoes the Maillard reaction, 20 further resulting in the degradation of sugars, and Amadori rearrangement products (ARPs), amino acid derivatives such as arginyl-fructose (AF) and arginyl-fructosyl-glucose (AFG) are formed at high levels (accounts for 3–4% of RG). 21 It was reported that the Maillard reaction can change the color and aroma of food, and the Maillard reaction products (MRPs) also have nutritional value and pharmacological effects such as immune modulatory activities, 22 anti-hyperglycemic, 23 nephroprotective, 24 and antioxidant properties, 25 and anti-inflammatory cytokines 26 in vitro and in vivo . With the increasing recognition of the various therapeutic effects of MRPs, AF and AFG as major non-saponin health foods or alternative medicine need to be thoroughly evaluated.…”