In fact, and interestingly, serum IgM concentration was increased after four weeks of the highest dose of hesperidin (Figure 7c)

In fact, and interestingly, serum IgM concentration was increased after four weeks of the highest dose of hesperidin (Figure 7c). Open in a separate window Figure 7 Effect of hesperidin administration throughout the study on serum (a) IgG; (b) IgA; and (c) IgM. also able to increase the small intestine IgA content. These changes in the small intestine were accompanied by a decrease in interferon- and monocyte chemotactic protein-1 concentration. In addition, hesperidin increased the relative proportion of TCR+ lymphocytes in MLNL. These results show the immunomodulatory actions of hesperidin around the gut-associated lymphoid tissue and reinforce its role as a prebiotic. Keywords: flavanone, flavonoids, immunoglobulin A, intestinal immunity, prebiotic, polyphenol 1. Introduction Polyphenols, extensively found in plants as a product of their secondary metabolism [1] can be classified into different groups regarding their chemical structure: Phenolic acids, flavonoids, anthocyanidins, stilbenes, and lignans [2]. Within the flavonoid family, the most distinguished subgroups are flavonols (e.g., quercetin, kaempferol, and myricetin), flavanones (e.g., eriodictyol, hesperetin, and naringenin), isoflavones (e.g., daidzein, genistein, and glycetein), flavones (e.g., apigenin, and luteolin), flavan-3-ols (e.g., catechin), and anthocyanins (e.g., cyanidin, delphinidin, and malvidin) [3]. The biological activity of flavonoids in human or animal health and their protective role in several diseases have been widely described [4,5]. There is a growing interest in flavonoids for their anti-inflammatory [6] and anti-diabetic [7] properties, as well as their microbial modulatory actions [8]. Olcegepant hydrochloride Hesperidin is the major flavanone present in citrus fruits, such as orange [9,10]. It is composed by hesperetin being conjugated to rutinose. After hesperidin intake, in the small intestine this flavanone is usually poorly assimilated via the paracellular pathway and it is highly dependent on the conversion to hesperetin [5,11]. Hesperidin reaches the large intestine where gut microbiota cleaves the attached rutinose moiety, forming hesperetin for further colonic absorption [12]. Hesperidin is usually gaining attention due to its different biological activities [3]. In this context, it has been considered a potential protective factor in neurodegenerative diseases [13], by reducing neuro-inflammation in experimental stroke [14]. Moreover, its anti-oxidant [15,16], Olcegepant hydrochloride anti-depressive [17], anti-cancer [18], and immunomodulatory properties have also been described [19,20,21,22,23]. In particular, hesperidin has been shown to increase the production of anti-inflammatory cytokines in vitro [19], to exert an anti-asthmatic effect [20,21], to alter the CD4/CD8+ T cell ratio in the intestine wall of mice infected with [22], and to influence the lymphocyte composition and functionality of the gut-associated lymphoid tissue Olcegepant hydrochloride in immunized rats [23]. Overall, the immunomodulatory properties of hesperidin were observed in vitro or in contamination/immunization models in which the immune system was triggered. Nevertheless, no studies have shown the immune effects of this flavanone in health status. On the other hand, as far as we know, Unno Rabbit polyclonal to ACVR2B et al. [24] in the only existing study around the influence of citrus flavanones around the gut microbiota, included them in rat food and showed the prebiotic-like effects of a hesperetin-enriched diet, but not a diet containing hesperidin. In this context, the relationship between the gut microbiota and the function of the gut-associated lymphoid tissue must be emphasized, as its close conversation are well established [25]. Indeed, the intestinal mucosa may be considered as an immunological niche as it hosts a complex immune-functional organ comprised of immunocompetent cells, their products, such as Olcegepant hydrochloride secretory IgA, and the microbiota [25]. While some studies have focused on the influence of hesperidin around the immune response, an in-depth investigation is needed into the effects of hesperidin around the gut-associated lymphoid tissue, which hesperidin reaches first, and moreover, where it can interact with gut microbiota contributing to the crosstalk between gut bacteria and intestinal immune tissue. Therefore, the aim of the present study was to establish the influence of oral hesperidin administration around the function of the gut-associated lymphoid tissue, including the mesenteric lymph node lymphocyte phenotype.