Purification and characterization of an antihypertensive peptide from a yogurt-like product fermented by Lactobacillus helveticus CPN4.
Whey peptides in a yogurt-like product fermented by Lactobacillus helveticus CPN4 were fractionated by a Sep-pak C-18 cartridge followed by two-step reverse-phase HPLC. The antihypertensive activity was measured by systolic blood pressure in spontaneously hypertensive rats after oral administration of each fraction. Five major peptides in the final fraction were further purified by reverse-phase HPLC and were measured for these antihypertensive activities in spontaneously hypertensive rats. The only peptide in the final fraction that showed strong antihypertensive activity had a sequence of Tyr-Pro, which is found in alpha s1-casein (CN), beta-CN, and kappa-CN. The synthetic peptide Tyr-Pro yielded significant antihypertensive activity from 2 to 8 h after oral administration of 1 mg of peptide/kg of body weight, and the effect was maximal at 6 h after oral administration. The antihypertensive effect of the peptide was dependent on the peptide dosage from 0.1 to 10 mg of peptide/kg of body weight. The concentration of Tyr-Pro peptide increased during fermentation and reached about 8.1 micrograms/ml of whey in the pH 4.3 yogurt-like product. The antihypertensive peptide had a low inhibitory activity against angiotensin I-converting enzyme. The inhibition of 50% of the angiotensin I-converting enzyme (IC50) was 720 microM.
R & D Center, Calpis Co., Ltd., Kanagawa, Japan.
N
N
Yamamoto
M
M
Maeno
T
T
Takano
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005285:Fermentation; D005511:Food Handling; D008297:Male; D008894:Milk Proteins; D051381:Rats; D011918:Rats, Inbred SHR; D013599:Systole / Q000187:drug effects*; D000067816:Whey Proteins; D015014:Yogurt / Q000032:analysis*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004151:Dipeptides; D008894:Milk Proteins; D000067816:Whey Proteins; C120594:tyrosyl-proline