• 한국축산식품학회지
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• 제35권6호
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• pp.831-840
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• 2015

Functionally and physiologically active peptides are produced from several food proteins during gastrointestinal digestion and fermentation of food materials with lactic acid bacteria. Once bioactive peptides (BPs) are liberated, they exhibit a wide variety of physiological functions in the human body such as gastrointestinal, cardiovascular, immune, endocrine, and nervous systems. These functionalities of the peptides in human health and physiology include antihypertensive, antimicrobial, antioxidative, antithrombotic, opioid, anti-appetizing, immunomodulatory and mineral-binding activities.

• Journal of Microbiology and Biotechnology
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• 제26권10호
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• pp.1675-1686
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• 2016

We characterized the probiotic properties of Lactobacillus helveticus strains KII13 and KHI1 isolated from fermented cow milk by in vitro and in vivo studies. The strains exhibited tolerance to simulated orogastrointestinal condition, adherence to Caco-2 cells, and antimicrobial activity. Both L. helveticus strains produced bioactive tripeptides, isoleucylprolyl-proline and valyl-prolyl-proline, during fermentation of milk. KII13 showed higher in vitro cholesterol-lowering activity (47%) compared with KHI1 (28%) and L. helveticus ATCC 15009 (22%), and hence, it was selected for in vivo study of cholesterol-lowering activity in atherogenic diet-fed hypercholesterolemic mice. For the study, mice were divided into four groups (viz., normal diet control group, atherogenic diet control group (HCD), KII13-atherogenic diet group (HCD-KII13), and Lactobacillus acidophilus ATCC 43121-atherogenic diet group (HCD-L.ac) as positive control). The serum total cholesterol level was significantly decreased by 8.6% and 7.78% in the HCD-KII13 and HCD-L.ac groups (p < 0.05), respectively, compared with the HCD group. Low-density lipoprotein cholesterol levels in both HCD-KII13 and HCD-L.ac groups were decreased by 13% and 11%, respectively, compared with the HCD group (both, p < 0.05). Analysis of cholesterol metabolism-related gene expression in mice liver showed increased expression of LDLR and SREBF2 genes in mice fed with KII13. By comparing all the results, we conclude that L. helveticus KII13 could be used as a potential probiotic strain to produce antihypertensive peptides and reduce serum cholesterol.

• Mycobiology
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• 제48권5호
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• pp.399-409
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• 2020

Many of the 𝛽-glucans are known to have antihypertensive activities, but, except for angiotensin-converting enzyme II inhibition, the underlying mechanisms remain unclear. Corin is an atrial natriuretic peptide (ANP)-converting enzyme. Activated corin cleaves pro-ANP to ANP, which regulates water-sodium balance and lowers blood pressure. Here, we reported a novel antihypertensive mechanism of 𝛽-glucans, involved with corin and ANP in mice. We showed that multiple oral administrations of 𝛽-glucan induced the expression of corin and ANP, and also increased natriuresis in mice. Microarray analysis showed that corin gene expression was only upregulated in mice liver by multiple, not single, oral administrations of the 𝛽-glucan fraction of Phellinus baumii (BGF). Corin was induced in liver and kidney tissues by the 𝛽-glucans from zymosan and barley, as well as by BGF. In addition to P. baumii, 𝛽-glucans from two other mushrooms, Phellinus linteus and Ganoderma lucidum, also induced corin mRNA expression in mouse liver. ELISA immunoassays showed that ANP production was increased in liver tissue by all the 𝛽-glucans tested, but not in the heart and kidney. Urinary sodium excretion was significantly increased by treatment with 𝛽-glucans in the order of BGF, zymosan, and barley, both in 1% normal and 10% high-sodium diets. In conclusion, we found that the oral administration of 𝛽-glucans could induce corin expression, ANP production, and sodium excretion in mice. Our findings will be helpful for investigations of 𝛽-glucans in corin and ANP-related fields, including blood pressure, salt-water balance, and circulation.

• 한국식품과학회지
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• 제38권4호
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• pp.567-570
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• 2006

본 연구는 항고혈압 활성이 있는 어육 단백질의 효소 가수분해물로부터 얻어진 peptide분말을 실험동물인 본태성 고혈압쥐(SHR)에게 음용수로 공급하여 혈압강하에 미치는 영향을 알아보기 위해 실시하였다. in vitro에서 멸치, 명태 그리고 고등어 가수분해물 500 ${\mu}g$을 첨가하여 각각 75, 81 그리고 35%의 ACE 저해활성을 보였던 펩타이드 분말 0.4167%을 희석하여 SHR에게 음용수로 공급한 후 생리적 변화를 관찰하기 위해 매 1주일 마다 총 섭취한 사료의 무게와 음수량을 측정하였다. 실험기간 중 SHR의 일당증체량은 명태(C)와 고등어처리군(D)이 각각 1.26 및 1.36 g으로 A군(0.78 g)과 B군(0.77 g) 보다 높았지만 유의적인 차이는 없었다. 사료섭취량은 $16.85{\sim}19.93$ g/day으로 거의 차이가 없었던 것으로 나타났다. 생후 13주령된 SHR를 대상으로 실험개시 전 측정한 기준혈압(RBP)은 실험군에서 평균 224mmHg 로 큰 차이가 없이 비슷하였다 어육 펩타이드 음용군(멸치, 동태, 고등어)은 경시적으로 감소경향을 나타냈으며 실험군 중 D군(고등어)의 수축기혈압은 투여 후 7일에 208mmHg로 측정되어 RBP 보다 15 mmHg가 감소하였고, 이 후 비슷한 수준을 유지하다가 28일에 191 mmHg로 실험군 중 가장 낮았다. C군(명태)은 투여 후 14일에 214mmHg로 측정되어 11 mmHg가 감소하였고, 28일에 202 mmHg로 나타났다. B군(멸치)은 투여 후 7일까지는 기준혈압(223 mmHg)과 비슷하였고, 이후 28일까지 203 mmHg로 일정한 수준을 유지하였다. 어육 펩타이드 대신 생수음용 대조군(A)은 실험기간 중 225-216 mmHg로 유의한 차이가 나타나지 않았다. 기준혈압(0일) 대비 28일의 혈압 감소치는 어육 펩타이드(멸치, 동태, 고등어) 음용군에서 각각 20, 23, 32 mmHg로 RBP대비 혈압감소율은 각각 9.0, 10.2, 14.3%로 나타났다.

• 한국수산과학회지
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• 제42권5호
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• pp.426-433
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• 2009

Fish scales have potential in functional food preparation due to their antioxidant and antihypertensive properties. We investigated the angiotensin I converting enzyme (ACE) inhibitory activity of Tilapia mossambica scale extracts. Hydrolysates of tilapia scales were prepared by enzymatic extraction using five proteases (${\alpha}$-chymotrypsin, Alcalase, Kojizyme, Protamex and trypsin) after scales were treated with hot water for 3 hr. Scale enzymatic hydrolysates prepared using both hot water and enzyme treatments exhibited elevated hydrolysis (about 25%-55%) compared to only enzyme treatment (about 15%-45%). Enzymatic hydrolysates (1 mg/mL) prepared by both hot water and enzyme treatments also showed significantly increased ACE inhibitory activities from about 20%-75%. The pattern of ACE inhibitory activities was similar to the degree of hydrolysis. Alcalase and ${\alpha}$-chymotrypsin hydrolysates displayed the highest ACE inhibitory activities ($IC_{50}$ = 0.83 mg/mL and 0.68 mg/mL, respectively). In addition, the ACE inhibitory effects of $IC_{50}$-chymotrypsin hydrolysates increased with decreasing molecular weight (5 kDa>, 10 kDa> and 30 kDa>), with the 5 kDa> fraction displaying the highest ACE inhibitory activity (about 89.9% and $IC_{50}$ = 0.1 mg/mL). We suggest that the peptide compounds of enzymatic hydrolysates prepared from tilapia scale enhances ACE inhibitory activity and might be useful as an antihypertensive material.

• 대한약리학회지
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• 제24권2호
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• pp.153-164
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• 1988

The potential role of endogenous opioid peptides (EOPS) in cardiovascular regulation has only recently been entertained. EOPS have been localized in brain, spinal cord, autonomic ganglia, particularly the adrenal gland, and many other peripheral tissues. There are at least five major types of opioid receptors; namely ${\mu},\;{\delta},\;k,\;{\sigma},\;and\;{\varepsilon}$ and Experimental evidence indicates that cardiovascular actions of the peptide are mediated primarily by ${\mu},\;{\delta}$ and k receptors, and that these receptor types may be allosterically coupled. In anesthetized rabbits met-enkephalin decreased blood pressure and heart rate, which closely paralleled a reduction in sympathetic discharge. Naloxone, but not naloxone methobromide, antagonized these effects, which suggests a central site of action of met-enkephalin. A number of autonomic agents, particularly adrenergic ${\alpha}$-and, ${\beta}-agonists$ and antagonists modify the cardiovascular actions of met-enkephalin. Experiments in reserpine-treated and adrenalectomized rats provide no evidence of sympathetic nervous system involvement in the pressor responses to intravenous injection of opioid peptides, but rather suggest a direct peripheral action. Finally, activation of a beta-endorphinergic pathway projecting from the arcuate nucleus to the nucleus tractos solitarii in rats can cause naloxone reversible hypotension and bradycardia. There is evidence to implicate this pathway in antihypertensive drug action and in the modulation of baroreflex activity.

• Journal of Animal Science and Technology
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• 제46권1호
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• pp.107-114
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• 2004

본 연구는 우둔 단백질에서 분리한 헥사펩타이드, VLAQYK의 자연발증 고혈압쥐의 혈압, 중성 지질, 그리고 콜레스테롤에 미치는 영향을 알아보기 위해 실시하였다. 헥사 펩타이드는 in vitro에서 138.34${\mu}\ell$/ml의 $IC_{50}$ 값을 보였던 것으로 농축하여 체중 kg당 각각 0.2g, 0.5g, 1.0g의 농도가 되도록 스테인레스 존데를 이용하여 경구투여한 후 혈압의 변화와 지질 수준을 살펴보았다. 실험기간동안 사료의 섭취량의 변화는 대체로 대조구와 처리구 사이에 크게 나타나지 않았지만 8주차에 이르러서는 대조군보다 세 처리구 모두 사료의 섭취량이 22 ${\sim}$ 24%로 감소하였다. 실험기간 동안 랫트의 체중의 변화는 비교적 저속적으로 증가하였지만 사료섭취에 대한 체중의 증가는 일정한 수준을 유지하여 경구 투여한 펩타이드에 대한 체중 증가는 없었다. 체내 중요 기관의 중량을 측정한 결과 대조군에 비해 간, 염통은 큰 변화가 없었으나 신장과 비장, 고환의 중량은 약간의 차이를 보였다. 신장의 중량은 0.2g과 0.5g의 헥사펩타이드 처리군에서 대조군보다 감소하였으며(P < 0.001), 비장은 대조군보다 오히려 중량이 증가 하였고(P < 0.05), 고환도 대조군보다 처리에 따라 중량의 증가를 보였다(P < 0.05). 헥사펩타이드를 체중 kg당 10.g의 농도로 투여한 군은 3주가 되자 대조군의 혈압보다 - 55.9mmHg로 저하되어 가장 강한 혈압 저하율을 보였으나(P < 0.05) 그 이루호는 6주째에 체중 kg당 0.2g의 농도로 투여한 구가 가장 높은 혈압 저하율을 보였다(P < 0.05). 실험 종료 후의 혈액내 총 콜레스테롤 함량은 0.2g, 0.5g, 1.0g의 헥사펩타이드의 모든 처리군에서 각각 대조군보다 25.4%, 23.5%, 23.7% 수준으로 더 낮은 농도를 보였다(P <0.001). 성인병 발병의 원인인 중성지질의 함량도 처리량에 따라 유의적으로 감소하여 113.3 ${\pm}$ 1.5mg 이었던 중성지방이, 0.5g/kg B.W의 헥사펩타이드 급여군에서는 93.6 ${\pm}$ 2.5mg의 수준으로 . 감소함을 보였다. 하지만 1.0g/kg B.W.의 헥사펩타이드의 급여군에서는 중성지질의 함량이 108.3 ${\pm}$ 1.5mg으로 증가하였다. 반면, HDL 콜레스테롤 함량은 대조군보다 모든 처리군에서 감소하는 경향을 보였으나 처리군 사이에서는 유의차를 보이지 않았다(P < 0.05). LDL 콜레스테롤 함량은 대조군바다 처리량에 따라 유의적으로(P <0.001) 감소하여 대조군에서 61.3 ${\pm}$ 1.7 이었던 것이 1.0gcjflrns에서는 36.4 ${\pm}$ 1.4mg의 함량으로 큰폭으로 감소하였음을 나타내었다. 본 연구의 결과를 종합하면, in vitro 상에서 ACE 억제 효과가 있었던 헥사펩타이드는 in vivo 상에서 농도 의존적인 혈압저하 효과를 보이지 못했지만 실험 개시후 3주에 가장 높은 혈압저하 수준을 보였고, 성인병의 발병지표로서 사용되는 LDL 콜레스테롤의 함량을 40.6%감소시켰다.

• Journal of Microbiology and Biotechnology
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• 제12권1호
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• pp.59-64
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• 2002

An angiotensin I-converting enzyme (EC 3.4.15.1) (ACE), which can convert inactive angiotensin I into angiotensin II, a vasoconstrictor, is one of the key enzymes in controlling hypertension. It is suggested that the inhibition of ACE prevents hypertension, and many inhibitory peptides have already been reported. In the current study, oligonucleotides encoding ACE inhibitory peptides (IY, VKY) were chemically synthesized and designed to be multimerised due to isoschizomer sites (BamHI, BglII). The cloned gene named AP3 was multimerised up to 6 times in pBluescript and expressed in BL2l containing pGEX-KG. The fusion protein (GST-AP3) was easily purified with a high recovery by an affinity resin, yielding 38 mg of synthetic AP3 from a 1-1 culture. The digestion of AP3 by chymotrypsin exhibited an $IC_50$ value of $18.53{\mu}M$. In conclusion, the present experiment indicated that AP3 could be used as a dietary antihypertensive drug, since the potent ACE inhibitory activity of AP3 could be activated by chymotrypsin in human intestine.

• Asian-Australasian Journal of Animal Sciences
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• 제16권9호
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• pp.1369-1373
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• 2003

ACE (Angiotensin-I converting enzyme) inhibitory peptides derived from foods are thought to suppress high blood pressure by inhibiting ACE. We tried to make efficient production of the ACE inhibitory hydrolysate from egg albumen. A hydrolysate digested by neutrase presented the highest ACE inhibitory activity ($IC_50\;value=256.35{\mu}g/ml$) and the proper proteolysis was occurred by 1.0% enzyme addition and 4 h incubation at $47^{\circ}C$. Antihypertensive effect of neutrase hydrolysate was investigated in spontaneously hypertensive rats (SHR, n=5). Systolic blood pressure (SBP) was decrease by 6.88% (-14.14 mmHg, p<0.05) at 3 h after oral administration of 300 mg/kg body weight, and by 13.33% (-27.72 mmHg, p<0.05) by emulsified hydrolysate. These results showed that it is very effective to utilize egg albumen as a protein source for the production of ACE inhibitory peptides. However, further studies are required to investigate the methods to increase recovery yield and the isolation of active peptide is necessary for determining its sequence responsible for ACE inhibitory activity.

• Fisheries and Aquatic Sciences
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• 제14권4호
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• pp.283-288
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• 2011

The jellyfish Nemopilema nomurai was hydrolyzed with papain and a novel dipeptide purified via ultrafiltration, gel filtration chromatography with Sephadex LH-20, and reverse phase chromatography using $C_{18}$ and $C_{12}$ columns. The IR, 1H NMR, 13C NMR, and MS spectrometer analyses showed that the dipeptide comprised tyrosine-isoleucine (Tyr-Ile). The $IC_{50}$ and $K_i$ values were $6.56{\pm}1.12$ and $3.10{\pm}0.28\;{\mu}M$, respectively, indicating competitive inhibition of angiotensin-I-converting enzyme (ACE). As a novel ACE-inhibitory active peptide, Tyr-Ile may have potential for use in antihypertensive therapy.