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Katsuobushi OligoPeptide

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Reference (Technical Reports) ”Katsuobushi Oligopeptide”

Classification and Antihypertensive Activity of Angiotensin 1-Converting Enzyme Inhibitory Peptides Derived from Food Proteins

■ Hiroyuki Fujita, Keiichi Yokoyama, and Masaaki Yoshikawa
■ Journal of Food Science Vol.65, No4, 564, 2000

<< Abstract >>
Angiotensin 1-converting enzyme (ACE)-inhibitory peptides from the thermolysin digest of chicken muscle and the peptic digest of ovalbumin were isolated. However, some of them failed to show antihypertensive activity in spontaneously hypertensive rats (SHR). To clarify this discrepancy，ACE-inhibitory peptide from various sources were preincubated with ACE before measurement of ACE-inhibitory peptides from various sources were preincubated with ACE before measurement of ACE-inhibitory activity and classified into 3 groups.(1) inhibitor type, IC50 values of peptides that are not affected after preincubation with ACE;(2)substrate type, peptides that are hydrolyzed by ACE to give peptides with weaker activity; and (3) prodrug-type inhibitor, these peptides are converted to true inhibitors by ACE or gastrointestinal proteases. Peptides belonging to the 1st and the 3rd groups exert antihypertensive activities even after oral administration in SHR. Key Words; angiotensin I-converting enzyme inhibitor, spontaneously hypertensive rat, ovalbumin, chicken muscle, bonito

Effect of an ace-inhibitory agent, katsuobushi oligopeptide, in the spontaneously hypertensive rat and in borderline and mildly hypertensive subjects

■ Hiroyuki Fujita, Tomohide Yamagami, Kazunori Ohsima
Research and Development Department, Nippon Supplement, Inc.,
Ohshima Clinic, Ibaraki, Osaka,
■ Nutrition Research 21 (2001) 1149

<< Abstract >>
It has been previously documented that the thermolysin digest of “Katsuobushi,” or dried bonito, a traditional Japanese food, potently inhibits the angiotensin I-converting enzyme (ACE). This hydrolyzate “Katsuobushi Oligopeptide(KO)” has antihypertensive effects in hypertensive subjects at a dose of 3g/day. In order to reduce the amount of KO required to produce an effect, we obtained a stronger KO (S-type KO) by ultra-filtration The S-type KO had two-fold higher ACE-inhibitory activity, and also showed two-fold higher antihypertensive activity in the spontaneously hypertensive rat after oral administration, compared with the original KO. In a human study, the antihypertensive effects of 1.5 g/day of S-type KO were monitored against a placebo in a double-blind, randomized, cross-over study in 61 borderline and mildly hypertensive subjects. S-type KO showed antihypertensive activity without any side-effects. Thus, the ACE-inhibitory S-type KO demonstrated more potent antihypertensive effects than the original formulation.

LKPNM: a prodrug-type ACE-inhibitory peptide derived from fish protein

■ Hiroyuki Fujita, Masaaki Yoshikawa
Nippon Synthetic Chemical Industry, Ibaraki-shi, Osaka 567-0052, Japan
Department of Functional Food Resources, Research Institute for Food Science,
Kyoto University, Kyoto 611-0011, Japan
■ Immunopharmacology 44 (1999) 123

<< Abstract >>
It has been previously documented that the thermolysin-digest of “Katsuo-bushi”, a Japanese traditional food processed from dried bonito possesses potent inhibitory activity against angiotensin I-converting enzyme (ACE). The present authors isolated eight kinds of ACE-inhibitory peptides from it. Of these isolated peptides, LKPNM (IC=2.4μM) was found to be hydrolyzed by ACE to produce LKP (IC=0.32μM) with 8-fold higher ACE-inhibitory activity relative to the parent peptide or LKPNM, suggesting that LKPNM can be regarded as a prodrug-type ACE-inhibitory peptide. For assessment of relative antihypertensive activities of LKPNM and LKP to that of captopril, they were orally a administered to SHR rats to monitor time-course changes of blood pressures, whereby it was evidenced that both LKPNM and captopril showed maximum effective doses of LKPNM and LKP accounted for 66% and 91% relative to that of captopril, respectively, whereas in vitro ACE-inhibitory activities of LKPNM and LKP were no more than 0.92％ and 7.73%compared with that of captopril (IC50=0.022μM). It is of interest to note that both of these peptides exert remarkably higher antihypertensive activities in vivo despite weaker in vitro ACE-inhibitory effects, which was ascertained by using captopril as the reference drug. which was ascertained by using captopril as the reference drug.

Katsuobushi OligoPeptide -Reference Report-

1.
Effects of an ACE-inhibitory peptide, Katsuobushi-oligopeptide, in the spontaneously hypertensive rat and in borderline and mildly hypertensive subjects.
Nutrition Research. 21, 1149-1158 (2001).
H. Fujita, T. Yamagami and K. Ohshima:

2.
Classification and antihypertensive activity of angiotensin I-converting enzyme inhibitory peptides derived from food proteins.
J. Food Sci., 65, 564-569 (2000).
H. Fujita, K. Yokoyama and M. Yoshikawa:

3.
LKPNM: a prodrug type ACE-inhibitory peptide derived from fish protein.
Immunopharmacology, 44(1), 123-127 (1999).
H. Fujita and M. Yoshikawa:

4.
A novel anti-hypertensive peptide derived from ovalbumin induces nitric oxide-mediated vasorelaxation in an isolated SHR mesenteric artery.
FEBS Letters, 452, 181 (1999)
M. Nobuyuki, H. Usui, H. Fujita and M. Yoshikawa:

5.
Human Volunteers Study on Antihypertensive Effect of “Katsuobushi Oligo Peptide”(Ⅰ)
Jpn Pharmacol Ther 147. Vol.25 No.8 1997
Fujita, R.Yasumoto, M.Hasegawa, K.Oshima

6.
Human Volunteers Study on Antihypertensive Effect of “Katsuobushi Oligo Peptide”(Ⅱ)　A Placebo-controlled Study on the Effect of “Peptide Soup” on Blood Pressure in Borderline and Hypertensive Subjects.
Jpn Pharmacol Ther 153　Vol.25 No.8 1997
Fujita, R.Yasumoto, M.Hasegawa, K.Oshima

7.
Ovokinin is an agonist for angiotensin AT2 receptors.
In Peptide Chemistry 1996, 134 (1997)
M. Yoshikawa, N. Matoba, R. Nakagiri, H. Fujita and M. Yoshikawa:

8.
Vasorelaxation by casomokinin L, a derivative of b-casomorphin and casoxin D, is mediated by NK1-receptor.
Peptides, 17, 635 (1996)
H. Fujita, H. Suganuma. H. Usui, K. Kurahashi, R. Sasaki and M. Yoshikawa

9.
Potentiation of anti-hypertensive activity of orally administered ovokinin, a vaso-relaxing peptide derived from ovalbumin, by emulsified in egg phosphatidylcholine,
Biosci. Biotechnol. Biochem., 59, 2344 (1995)
H. Fujita, R. Sasaki and M. Yoshikawa:

10.
Isolation and characterization of 5. ovokinin, a bradykinin B1 agonist peptide derived from ovalbumin.
Peptides, 16, 785 (1995)
H. Fujita, H. Usui, K. Kurahashi and M. Yoshikawa

11.
Ovokinin, a bradykinin B1 agonist peptide derived from ovalbumin.
In Peptide Chemistry 1994, (1995) pp.272
H. Fujita, et al.

12.
Anti-hypertensive effect of thermolysin digest of dried bonito in spontaneously hypertensive rat (SHR).
Clinical and experimental Pharmacology and Physiology, Suppl. 1, S304 (1995)
H. Fujita, K. Yokoyama, R. Yasumoto and M. Yoshikawa:

13.
Studies on the optimum conditions to utilize biologically active peptides derived from food proteins.
In Developments in Food Engineering, (1994) pp.1053
M. Yoshikawa and H. Fujita:

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