Edible Bird’s Nest attenuates high fat diet-induced oxidative stress and inflammation via regulation of hepatic antioxidant and inflammatory genes

High fat diet-induced weight gain is often accompanied by oxidative stress [11, 12]. In this study, high fat diet increased weight gain and induced oxidative stress, which were attenuated by EBN feeding (Table 1 & Fig. 1). The results indicate that while high fat diet promoted oxidative stress relative to normal group, EBN significantly attenuated such a response, although no significant differences were observed between the EBN groups. Moreover, increased weight has been associated with low grade inflammation and other cardiometabolic health problems [13]. The level of TBARS in the Simvastatin group was also lower than in the untreated control group, but not significantly so. Furthermore, antioxidant status in the different groups indicated that high fat diet reduced antioxidants in comparison with the normal group, while EBN prevented such an effect. Simvastatin was similarly able to prevent reduction in antioxidant status. The ability of EBN to reduce oxidative stress has been ascribed to its antioxidant content, as demonstrated in our recent publication where EBN was shown to possess potent antioxidant abilities that contributed towards lowering of oxidative sterss markers [4]. This is similar to what has been reported on the ability of antixidants to scavenge free radicals thereby lowering oxidative stress [14]. Conversely, the weight and oxidative stress modulatory effects of Simvastatin in rats have been reported previously [15].

In the present study, EBN also attenuated EBN-induced inflammatory response after 12 weeks of intervention (Fig. 2). C-reactive protein (CRP), interleukin (IL) 6 and tumor necrosis factor alpha (Tnf-α) were lower in the EBN and Simvastatin groups. These results are in agreement with previous findings on the anti-inflammatory effects of EBN and Simvastatin [16]. Elevated CRP and IL6 have been reported as important markers of the inflammatory response [17], while Tnf-α is involved in the mediation of a number of processes including the inflammatory process [18]. Moreover, decreases in serum levels of these markers (CRP, IL6 and Tnf-α) has been associated with reduced inflammation [17, 18], and therefore, the present results suggest that EBN has anti-inflammatory effects in in vivo systems. It will be recalled that the anti-inflammatory effects of EBN have thus far been reported using in vitro system [3], and our report provides more insight into such effects.

Based on the antioxidant and anti-inflammatory effects shown by EBN, we evaluated its effects on hepatic antioxidant and inflammation-related genes (Table 1). High fat diet feeding suppressed the expression of hepatic antioxidant genes (Fig. 3; superoxide dismutase [SOD] 1 and 2, glutathione reductase [Gsr], and glutathione peroxidase [Gpx]), while EBN increased their expression. The results suggest that increased expression of antioxidants through transcriptional regulation may partly underlie the increased antioxidant status in the rats that consumed EBN. Moreover, increased expression of hepatic antioxidant genes has been associated with improved antioxidant status [19]. Also, EBN showed a dose-dependent effect on the expression of antioxidant genes but not serum total antioxidant status possibly because post-transcriptional modifications produced effects to the same degree irrespective of the degree of transcriptional changes induced. The results suggest that EBN will ultimately produce an all-or-none effect notwithstanding the transcriptional changes.

Furthermore, high fat diet feeding increased expression of inflammatory genes (Fig. 4; CRP Tnf-α, chemokine [C-C motif] ligand 2 [CCL2], and nuclear factor Kappa B [nfkb]1), while EBN prevented these high fat diet-induced changes. Increased expression of hepatic inflammatory markers and suppression of the anti-inflammatory marker suggested that high fat diet favoured an increased inflammatory response, in keeping with earlier findings [13]. EBN, on the other hand, prevented the increase in expression of hepatic inflammatory markers, which may underlie the reduced serum inflammatory markers observed in this study; CRP and Tnf-α were reduced in the serum of the EBN groups. However, just as we observed for the hepatic antioxidant genes, the dose-dependent transcriptional changes induced by EBN were not reflected by the results of the serum biomarkers. As can be recalled, these observations may be due to post-transcriptional modifications that produce an all-or-none effect. Interestingly, despite lack of effect of EBN on the expression of the IL6 gene (data not shown), we observed a change in its serum levels. The reduced serum IL6 despite lack of any transcriptional effect of EBN on the IL6 gene EBN further supports our hypothesis that EBN may have multiple targets, and that the transcriptional changes observed in this study may only partly explain the antioxidant and anti-inflammatory effects of EBN. It is clear that other mechanisms are involved in these effects, and are worth studying further.

In aggregate, the ability of EBN to prevent high fat diet-induced weight gain, oxidative stress and inflammation suggests that it may be used as supplement to prevent obesity-associated inflammation and consequent cardiometabolic problems. Already, there are indications that inflammation due to obesity may underlie the cardiovascular and other metabolic diseases that are sequelae of excessive weight gain [13], and hence EBN may be a good supplement for these problems since it can prevent inflammation, oxidative stress and weight gain. Recently, we demonstrated that the EBN used in this study is predominantly made up of proteins and its effects were likely mediated through synergistic effects of its protein bioactives including sialic acid, lactoferrin and ovotransferrin [8]. Other bioactives may be contributing to this synergistic effect, and these findings are worth evaluating further. The presence of contaminants has also been reported in EBN, which may counter any beneficial effects of EBN. Therefore, future endeavours at studying the health effects of EBN and especially its commercialization must employ stringent screening methods to ensure no toxicity from consumption of EBN.