Food peptides are being viewed as vital ingredients of functional foods, as well as nutraceuticals that could be used to promote good health, and lower the risks of getting certain types of chronic illnesses. But, though it has been shown that peptides have a variety of health benefits, including the ability to assert multiple benefits by chemical assays, animal models, and cell culture, it has been an arduous and time-consuming task to translate the new findings into commercial or practical applications.
This has been the case due to the lack of proper correlation between vitro findings with in vivo functions of peptides, as a result of their low bioavailability. Following the ingestion of a peptide, it is vital for them to resist the actions of digestive enzymes, as they make their way through the gastrointestinal tract, and cross the epithelial walls of the cell membranes, so that they can get into the bloodstream and head over to the target organs or target cells, where their health-promoting properties are to be utilized.
Hence, for a proper understanding of the in vivo physiological effects of food bioactive peptides, there is a need for extensive research to be done on the stability of the gastrointestinal tract, and the most appropriate means of transport. In this brief review, we will look at some of the current strategies being used to enhance the bioavailability of food peptides, and the current approaches being considered to overcome the roadblocks that have hindered the proper assimilation of peptides, once they are ingested.
It should be noted that once the mechanisms responsible for the transportation of bioactive peptides, as well as the factors responsible for their absorptions are known and properly understood, it will become easier to design and formulate a variety of strategies, which can then be used to enhance the bioavailability of peptides, in addition to maintaining their potency in vivo bioactivities.
The goal of these strategies is to achieve objectives, such as reducing the detrimental effects of food processing on the potency of peptides, promoting the desirable interaction between peptides and other food matrix components, protecting bioactive peptides from the actions of gastrointestinal enzymes and juices, controlling the release of peptides directed at the target sites, and improving the transportation of bioactive peptides through the walls of the small intestines to the target cells.
Below is a brief look at some of the strategies that are currently being explored, to improve the bioavailability of food peptides:
The application of new food processing techniques
There are certain food processing techniques that have been used for years in ensuring that food is well preserved, and their microbial safety is not compromised in any way. Some of these approaches include evaporation, drying, pasteurization, and sterilization. However, it is well known that temperature has detrimental effects on certain food components, since it can damage the structure of the peptides, in addition to affecting bioactivity.
Consequently, in the recent past, there has been a heavy focus on non-thermal techniques, which have been properly designed and optimized, with the goal of reducing the negative effects, as well as increasing the bioaccessibility, bioactivity, and bioavailability of food peptides. Application of methods, such as ultra-high hydrostatic pressure, irradiation, microwave, pulsed electric field, and ultrasounds have emerged, with the ability to inactivate microorganisms at near room temperature, leading to the preservation of the sensory, nutritional, and functional qualities of the food products.
However, there is still limited data regarding the potential effects of non-thermal food processing, and preservation techniques on the bioactivity, as well as the bioavailability of food peptides. As such, there is a need for further studies to be conducted, so as to gain more insights into how the non-thermal food processing and preservation techniques could affect the vital properties and characteristics of food-derived peptides.
Structure and property modification for peptides
To shield food-derived peptides from the detrimental effects of digestive enzymes, potentiate their biological activities, and improve their intestinal permeability, it may be necessary to improve the peptide’s structure in a number of ways.
When changes are done to the C- and N- amino acid terminals through amidation or acetylation, it has been observed that it is possible to protect the peptide from the destructive actions of carboxypeptidases and amino-. Another biochemical feature believed to increase the peptides’ resistance to exopeptidase degradation, is the process of cyclization. This process has also been shown to enhance the stability of the peptides, as well as increase their half-life, while in the gastrointestinal environment.
Additionally, when modifications are done inside the peptide chain, it is possible to realize huge improvements regarding the biological activities of the peptides. Hence, processes such as phosphorylation of hydroxyl groups of serine, may prevent the hydrolysis of food peptides by certain digestive enzymes, improve the absorption of the enzymes, and protect the enzyme’s capacity for mineral binding. In a study conducted by Tanzadehpanah et al., whereby they studied the effects of two peptides that differed only on the last amino acid, it was observed that the presence of proline improved the ACE-inhibitory activities of one peptide, while it improved the antioxidant and antimicrobial activities of the other peptide.
It has also been suggested that by changing the molecular mass, as well as the structure of peptide-based compounds, it may be possible to have a positive effect on the permeation that usually takes place across the intestinal mucosa. However, there is still not enough data regarding the effects of these modifications on the absorption ability of food-derived peptides, hence, further work is required, in order to produce more detailed conclusions.
Protease and Peptidase Inhibitors
The administration of peptides in conjunction with protease/peptidase inhibitors, has been shown to inhibit the degradation of certain types of peptides when in the gastrointestinal tract, hence, enhancing the intestinal absorption of the peptides. In as much as synthetic peptides have been widely used in protecting peptide-based compounds, natural inhibitors, such as Kunitz trypsin and Bowman-Birk protease inhibitor (BBI), are currently the preferred options owing to the fact that they come with lower side effects, and they are also compatible with a variety of food-derived peptides.
Therefore, BBI has been able to protect soybean peptide, known as lunatic from in vitro gastrointestinal digestion, and in so doing, it improves both its absorption capacity and bioavailability. However, there are serious drawbacks that have been associated with the application of protease inhibitors, in such a manner. Since they are susceptible to enzymatic degradation in the gut environment, the co-administration with the peptides, needs to be in high doses before the protective effects can be realized.
The chronic and prolonged administration of enzyme inhibitors, may end up changing the metabolic patterns of the gut environment, increasing the likelihood of inappropriate digestion of nutritive proteins. It is also possible that they can provoke an endogenous regulatory mechanism, which might end up stimulating the production of digestive peptidase.
The use of absorption enhancers
Absorption enhancers simply refer to substances that allow bioactive compounds to become more permeable across the walls of the small intestines, also known as the intestinal epithelium, into the systemic circulation, and to successfully reach the target cells or organs, where they are to release their biological activities.
There have been several mechanisms of actions that have been proposed for the functioning of absorption enhancers, with some of the most popular ones being their ability to reduce the mucus viscosity on the epithelial membrane, the reduction of the aperture of the TJs, increasing the fluidity of the epithelial membrane, and disrupting the structural integrity of the intestinal barrier. This facilitates the molecules’ ability to pass through. Ideal absorption enhancers should possess certain features that ensure they are not a danger to the molecules whose transportation they are supposed to enhance. For example, absorption enhancers should be non-toxic, non-allergenic, chemically inert, safe and pharmacologically stable.
However, just like protease inhibitors, one of the greatest limitations concerning the use of absorption inhibitors, is that their long-term use can lead to serious damages to the intestinal membranes, leading to local inflammation, among other conditions, whose long-term consequences may not be desirable at all. Also, the use of absorption enhancers may potentially introduce certain unwanted substances into the bloodstream.
Of all the absorption enhancers that have the potential to improve the oral bioavailability of peptides and proteins, the ones that have received a lot of attention, include bile salts, cationic and ionic polymers, chelating agents, surfactants, and fatty acids, and fatty acid derivatives. Though absorption enhancers have been extensively used in pharmacological setups, their application in improving the bioavailability of peptide-based compounds such as insulin, and recombinant human growth hormone, as well as their application in the food industry, is still severely limited.
However, there are certain food-grade absorption enhancers like chitosan, fatty acids, and citric acids, which have showed promising results to-date, and they are currently being viewed as very good candidates for the development of bioactive peptide-based functional foods and nutraceuticals.
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