In modern society, lifestyle-related diseases concomitant with chronic diseases, such as atherosclerosis, heart disease, stroke, obesity, and type 2 diabetes, have been rapidly increased as a critical public health issue in the world [1]. It is estimated that there are approximately 60 million deaths worldwide each year, in which over half are related to lifestyle-related diseases. The classes of diseases can be improved by lifestyle changes and early treatments such as healthy diet, non-smoking, reducing excessive alcohol use, reducing stress level, and regular exercise [2].   

It is well known that a healthy diet plays an important role in disease prevention or modulation. For this reason, food scientists have researched the physiological activities of food compounds, in particular, bioactive peptides from food proteins, which can exert positive physiological responses in the body upon their basic nutritional compositions in the provision of nitrogen and essential amino acids [3]. It has been demonstrated that bioactive peptides are essential in the prevention of lifestyle-related diseases such as hypertension [4–8], antioxidation [9], and inflammation [3]. Thus far, many peptides with various bioactive functions have been discovered and identified [9–12]. It was known that peptides generally consisting of 2 to 9 amino acids may elicit bioactivities [5,9]. Among them, small peptides showing antihypertensive activity by angiotensin-converting enzyme (ACE) inhibition, renin inhibition, and calcium channel blocking effects are in common [13].

The source of food-derived bioactive peptides is mainly from dietary proteins (milk, meat, egg, and soybean) [6,9,14–16]. So far reported, Sipola et al. [17] demonstrated that a long-term administration (12 weeks) of peptides (Ile-Pro-Pro and Val-Pro-Pro) or sour milk containing both tripeptides to 12- and 20-wk spontaneously hypertensive rats (SHR) resulted in a significant decrease in systolic blood pressure (SBP) of 12 or 17 mmHg, respectively. A dipeptide, Val-Tyr, from sardine muscle hydrolysate, showed a significant clinical antihypertensive effect in mild hypertensive subjects [6]. Trp-His and His-Arg-Trp were reported to block L-type Ca2+ channels [18,19]. Vallabha et al. [11] identified peptides including Leu-Ile, Leu-Ile-Val, Leu-Ile-Val-Thr, and Leu-Ile-Val-Thr-Gln from soybean hydrolysate with ACE inhibitory activity. A series of oligopeptides Phe-Asp-Ser-Gly-Pro-Ala-Gly-Val-Leu and Asn–Gly-Pro-Leu-Gln-Ala-Gly-Gln-Pro-Gly-Glu-Arg from squid [20]; Asp-Ser-Gly-Val-Thr, Ile-Glu-Ala-Glu-Gly-Glu, Asp-Ala-Gln-Glu-Lys-Leu-Glu, Glu-Glu-Leu-Asp-Asn-Ala-Leu-Asn, and Val-Pro-Ser-Ile-Asp-Asp-Gln-Glu-Glu-Leu-Met in hydrolysates produced from porcine myofibrillar proteins [12] were found to have antioxidant activity. Other reported peptides were also demonstrated to have physiological activities in preventing lifestyle-related diseases, as summarized in Table 1. Although bioactive peptides from functional foods are less effective than therapeutic drugs by daily intake, peptides must play a crucial role as a natural and safe diet in disease prevention.

Table 1. Reported physiological functions of peptides from food proteins








Enzymatic hydrolysis

Val-Tyr, Met-Phe, Arg-Tyr, Met-Tyr, Leu-Tyr, Tyr-Leu, Ile-Tyr, Val-Phe, Gly-Arg-Pro, Arg-Phe-His, Ala-Lys-Lys, Arg-Val-Tyr

ACE inhibition


Soy bean

Enzymatic hydrolysis

Leu-Ile, Leu-Ile-Val, Leu-Ile-Val-Thr, Leu-Ile-Val-Thr-Gln

ACE inhibition




Ile-Pro-Pro, Val-Pro-Pro




Pepsin, chymotrypsin, trypsin hydrolysis

Val-Lys, Tyr-Gln, Tyr-Gln-Tyr, Pro-Ser-Tyr, Leu-Gly-Ile, Ile-Thr-Phe, Ile-Asn-Ser-Gln

ACE inhibitory



Trypsin hydrolysis

Phe-Asp-Ser-Gly-Pro-Ala-Gly-Val-Leu, Asn–Gly-Pro-Leu-Gln-Ala-Gly-Gln-Pro-Gly-Glu-Arg



Porcine myofibrillar proteins

Enzymatic hydrolysis

Asp-Ser-Gly-Val-Thr, Ile-Glu-Ala-Glu-Gly-Glu, Asp-Ala-Gln-Glu-Lys-Leu-Glu, Glu-Glu-Leu-Asp-Asn-Ala-Leu-Asn, Val-Pro-Ser-Ile-Asp-Asp-Gln-Glu-Glu-Leu-Met



Defatted soy protein

Thermolase hydrolysis




Soybean glycinin

Enzymatic hydrolysis




α’ subunit of β-conglycinin

Enzymatic hydrolysis

Soymetide-13: Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn-Lys-Pro-Gly-Arg

Soymetide-9: Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn

Soymetide-4: Met-Ile-Thr-Leu

Immunostimulation; sometide-9 showed the most active in stimulating phagocytosis in vitro


Soybean conglycinin

Protease S hydrolysis

Val-Asn-Pro-His-Asp-His-Gln-Asn, Leu-Val-Asn-Pro-His-Asp-His-Gln-Asn, Leu-Leu-Pro-His-His, Leu-Leu-Pro-His-His




Many researchers have focused on biologically active peptides present in the sequences of food proteins. Food-derived bioactive peptides as functional foods are expected to be effective in preventing lifestyle-related diseases and maintaining the physical and well-being of humans due to their physiological benefits such as antihypertensive [4–8], antioxidant [9], and anti-inflammatory effects [3]. Industrial manufacturers, thus, need to control the quality and quantity of peptides for the development of functional foods.


Figure 1. Schematic diagram for peptide absorption in intestinal tract

The potential physiological effect of a peptide depends on the ability to reach target organ in an active or intact form after oral administration. It was believed that dietary proteins were completely hydrolyzed into their constituent amino acids, and then absorbed into blood via specific amino acid transport systems until the report by Newey and Smyth, who provided the first convincing evidence that dipeptides could be absorbed in intact form. Apart from the aforementioned di-/tripeptides, much work has been focused on the absorption of oligopeptides, since many oligopeptides have been demonstrated to play physiological preventive roles in events against lifestyle-related diseases [13]. In vitro studies reported that oligopeptides could be transported across the brush border membrane. Reecently, Hanh et al. [26] demonstrated for the first time that oligopeptides can be absorbed in vivo in a peptide length-dependent manner of di- > tri- > tetra- > pentapeptide length (Figure 1).



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           Vu Thi Hanh – Faculty of food science and technology