# Phytoglycoproteins and Human Health: Current Knowledge and Future Applications
## 4 Perspective on Bioavailability and Safety of Phytoglycoprotein  
Despite the numerous bioactivities and health benefits attributed to glycoproteins and other drug-like phytochemicals, their effectual activities in humans greatly depend on their bioavailability and relative toxicity dose [58]. Bioavailability in humans refers to the effective amounts of bioactive substances that can successfully cross the intestinal epithelia barrier into the circulatory system and reach the designated cells where they elicit their physiological effects. Bioavailability of orally delivered molecules depends on the level of intestinal epithelia permeation, availability of specific transporters, and activation or inhibition of the efflux of permeability glycoproteins (P-glycoprotein) [59]. Although some biological activities of PGPs were observed in animal models, there are sparingly available studies on the bioavailability and toxicity profile of the PGPs. Generally, factors that could influence the bioavailability and toxicity of PGPs include the bulkiness and structural complexity, nature of glycosylation, constituent of polypeptide backbone, and susceptibility to hydrolytic/digestive enzymes in the gastrointestinal tract [60]. The bulkiness of PGPs depends on the nature and the number of the oligo-glycan moieties attached to the polypeptide chains by N- or O- linkages. Bulky and heavily glycosylated PGPs, which may reflect in their high molecular weight, would not easily permeate through intestinal mucus layer and epithelia [60]. More so, the potential therapeutic effects of PGPs depend on the type and position of glycosylation in the polypeptides. Studies from synthetic glycosylation of therapeutic peptides showed that N-glycosylated peptides are more readily bioavailable and show better therapeutic profiles than O-glycosylated peptides [61]. Notably, the susceptibility of PGPs to hydrolytic or digestive enzymes in the gastrointestinal could reduce their bioavailability and physiological bioactivities [62]. Stability of glycoproteins has been shown to be affected by the number and type of glycosylation irrespective of the glycoprotein source. This is because deglycosylation generally impacts negatively on the pH, temperature and salt/alcohol stability of glycoproteins [63; 64]. Unlike bioactive peptides whose biostability has been shown to depend on the chain length, net charge and physicochemical properties of the amino acid compositions [65; 66; 67], there is a dearth of information on the stability of dietary glycoproteins to enzymatic degradation during gastrointestinal transport and in circulation before reaching the target tissues. Considering that the majority of the biological activities of PGPs are reported in cell culture studies, further research should clarify the influence of the type and number of monosaccharides in oligosaccharideside moieties in glycoproteins on the biostability, bioavailability and in vivo biactivities. A study by [PERSON] et al. [57] claimed that _Undaria pinnatifida_ PGPs exhibited partial biostability to intestinal enzymatic hydrolysis in simulated experiment, but this was based on retention of bioactivity. To properly establish biostability, changesin the primary structure of PGPs need to be monitored at the different digestion phases. Prior to digestion and intestinal uptake, other components of the food matrix, such as micronutrients, may influence the transport, stability and bioactivities of peptides [68, 69, 70, 71, 72, 73] and dietary polyphenols [74, 75]. Based on this, further studies should investigate the effects of the vehicle or food matrix containing the PGPs on their biostability and bioaccessibility and consequently their bioavailability. Table 1 shows the structural properties and bioactivities of several phytoglycoprotein. All the cell-based studies discussed in this review used PGPs in their intact forms to observe the health-promoting or beneficial effects.