257
was isolated and orally given to spontaneously hypertensive rates which showed a
significant decrease in their blood pressure levels (Murakami et al. 2004).
Because pharmacological drugs have strong side effects in hypertensive patients,
ACE inhibitor peptides from foods may provide an alternative and natural option to
regulate blood pressure (Mohanty et al. 2016). However, to prove the efficacy of
these peptides in vivo still remains a challenge. This is because peptides need to
reach the target organ in their active and intact form once orally ingested. For this
purpose, several studies have been carried out to evaluate the resistance of small
antihypertensive peptides to gastrointestinal digestion in cell line models (Quiros
et al. 2008; Contreras et al. 2012; Picariello et al. 2013). Another important factor to
consider is the association between in vitro and in vivo experiments. Various studies
has reported that some peptides that showed potent antihypertensive activity in vitro
failed to exhibit the same effects in animal models. For instance, no hypotensive
effect of αs1-casein f(23–27) was observed in anesthetized rats in contrast to significant ACE inhibitory activity in vitro (Maruyama et al. 1987); presumably due to
deterioration to inactive fragments during oral ingestion (FitzGerald et al. 2004).
This suggests that although valuable information from in vitro studies is obtained,
only in vivo studies can encompass important parameters like nature, mechanism
and bioavailability and reliably assess the hypotensive effects of a given peptide
(FitzGerald et al. 2004; Vermeirssen et al. 2004). Several fermented milk products
(yogurt, drinks, hydrolyzed milk) are available in the markets that contain the ACE
inhibitory peptides such as IPP, VPP, RY and TTMPLW. Specifically, casein hydrolysate (Casein DP, Kanebo Ltd., Japan), whey protein hydrolysate (Biozate, Davisco,
US), and C12 peptide (DMV, the Netherlands) have been developed for consumption (FitzGerald et al. 2004). Valio Company in Finland, for instance, has developed
two fermented dairy products with IPP and VPP peptides (FitzGerald et al. 2004;
Gobbetti et al. 2004), while a lacto tri-peptide is an alternative to drugs available to
maintain blood pressure (Jäkälä and Vapaatalo 2010).
A few epidemiological studies have also shown the association between milk
consumption and hypertension, where individuals with low to non-milk consumption had a higher incidence of hypertension (McCarron et al. 1984; Garcia-Palmieri
et al. 1984). Clinical trials have also shown decreased blood pressure by ACE inhibitory peptides from fermented milk (Seppo et al. 2003). Lactotripeptides from
casein hydrolysate were reported to modulate pulse wave velocity in mildly hypertensive subjects (Cicero et al. 2011, 2016). Thus, such peptides may be a safe and
natural alternative to synthetic drugs, although their potency is not the same as the
pharmacological ones (Sharma et al. 2011).
Opioid Properties
Milk-derived opioid peptides are those which have structurally similar sequences to
endogenous peptides (Table 3). They are opioid receptor ligands hidden within
bovine and human β-casein and released enzymatically in vitro (Brantl 1984). Other
Nutraceutical Properties of Bioactive Peptides
was isolated and orally given to spontaneously hypertensive rates which showed a
significant decrease in their blood pressure levels (Murakami et al. 2004).
Because pharmacological drugs have strong side effects in hypertensive patients,
ACE inhibitor peptides from foods may provide an alternative and natural option to
regulate blood pressure (Mohanty et al. 2016). However, to prove the efficacy of
these peptides in vivo still remains a challenge. This is because peptides need to
reach the target organ in their active and intact form once orally ingested. For this
purpose, several studies have been carried out to evaluate the resistance of small
antihypertensive peptides to gastrointestinal digestion in cell line models (Quiros
et al. 2008; Contreras et al. 2012; Picariello et al. 2013). Another important factor to
consider is the association between in vitro and in vivo experiments. Various studies
has reported that some peptides that showed potent antihypertensive activity in vitro
failed to exhibit the same effects in animal models. For instance, no hypotensive
effect of αs1-casein f(23–27) was observed in anesthetized rats in contrast to significant ACE inhibitory activity in vitro (Maruyama et al. 1987); presumably due to
deterioration to inactive fragments during oral ingestion (FitzGerald et al. 2004).
This suggests that although valuable information from in vitro studies is obtained,
only in vivo studies can encompass important parameters like nature, mechanism
and bioavailability and reliably assess the hypotensive effects of a given peptide
(FitzGerald et al. 2004; Vermeirssen et al. 2004). Several fermented milk products
(yogurt, drinks, hydrolyzed milk) are available in the markets that contain the ACE
inhibitory peptides such as IPP, VPP, RY and TTMPLW. Specifically, casein hydrolysate (Casein DP, Kanebo Ltd., Japan), whey protein hydrolysate (Biozate, Davisco,
US), and C12 peptide (DMV, the Netherlands) have been developed for consumption (FitzGerald et al. 2004). Valio Company in Finland, for instance, has developed
two fermented dairy products with IPP and VPP peptides (FitzGerald et al. 2004;
Gobbetti et al. 2004), while a lacto tri-peptide is an alternative to drugs available to
maintain blood pressure (Jäkälä and Vapaatalo 2010).
A few epidemiological studies have also shown the association between milk
consumption and hypertension, where individuals with low to non-milk consumption had a higher incidence of hypertension (McCarron et al. 1984; Garcia-Palmieri
et al. 1984). Clinical trials have also shown decreased blood pressure by ACE inhibitory peptides from fermented milk (Seppo et al. 2003). Lactotripeptides from
casein hydrolysate were reported to modulate pulse wave velocity in mildly hypertensive subjects (Cicero et al. 2011, 2016). Thus, such peptides may be a safe and
natural alternative to synthetic drugs, although their potency is not the same as the
pharmacological ones (Sharma et al. 2011).
Opioid Properties
Milk-derived opioid peptides are those which have structurally similar sequences to
endogenous peptides (Table 3). They are opioid receptor ligands hidden within
bovine and human β-casein and released enzymatically in vitro (Brantl 1984). Other
Nutraceutical Properties of Bioactive Peptides