In silico and in vivo experiment of soymilk peptide (tetrapeptide - FFYY) for the treatment of hypertension

IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Peptides Pub Date : 2024-02-09 DOI:10.1016/j.peptides.2024.171170
Md Alauddin , Md. Ruhul Amin , Muhammad Ali Siddiquee , Kazuyuki Hiwatashi , Atsushi Shimakage , Saori Takahashi , Mamoru Shinbo , Michio Komai , Hitoshi Shirakawa
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Abstract

Enzyme-Treated Soymilk (ETS) was produced from Commercial Soymilk (CSM) with the treatment of proteinase PROTIN SD-NY10 (Bacillus amyloliquefaciens). Previously, we have isolated novel peptides from ETS but data related to isolated-peptides are scant. In this study, bio-informatics and in vivo analysis of isolated-peptides showed strong binding affinity to the active site of the Angiotensin Converting Enzyme (ACE). Among four peptides, tetrapeptide Phe-Phe-Tyr-Tyr (FFYY) showed strong binding affinity and inhibitory activity to the ACE-enzyme (binding affinity −9.5 Kcal/mol and inhibitory concentration of 1.9 µM respectively) as well as showed less toxicity compared to other peptides. The animal experiment revealed that single oral dose of FFYY (80 µg/kg body weight/day) effectively ameliorates the systolic, diastolic and mean blood pressure in the spontaneously hypertensive rat (SHR) model. Chronic oral administration of FFYY (80 µg/kg body weight/day for 3 weeks) reduced the systolic blood pressure elevation and ACE activity without any adverse side effects on the physiological and biological parameters of SHR. In conclusion, both in silico and in vivo experiments of soymilk-isolated FFYY peptide showed a promising option as a potential alternative for hypertension treatment without adverse side effects on SHR.

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豆浆肽(四肽 - FFYY)治疗高血压的硅学和体内实验。
酶处理豆奶(ETS)是由商用豆奶(CSM)经蛋白酶 PROTIN SD-NY10 (淀粉芽孢杆菌)处理后制成的。此前,我们曾从 ETS 中分离出新型多肽,但与分离肽相关的数据却很少。在这项研究中,对分离肽的生物信息学和体内分析表明,它们与血管紧张素转换酶(ACE)的活性位点有很强的结合亲和力。在四种肽中,四肽 Phe-Phe-Tyr-Tyr(FFYY)对 ACE 酶具有很强的结合亲和力和抑制活性(结合亲和力为 -9.5 Kcal/mol,抑制浓度为 1.9µM),而且与其他肽相比毒性较小。动物实验显示,单次口服 FFYY(80µg/kg 体重/天)可有效改善自发性高血压大鼠(SHR)模型的收缩压、舒张压和平均血压。长期口服 FFYY(80µg/kg 体重/天,连续 3 周)可降低 SHR 收缩压升高和 ACE 活性,且不会对其生理和生物参数产生任何不良副作用。总之,豆浆分离的FFYY肽的硅学和体内实验都表明,它是一种很有前景的治疗高血压的潜在替代品,而且不会对SHR产生不良副作用。
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来源期刊
Peptides
Peptides 医学-生化与分子生物学
CiteScore
6.40
自引率
6.70%
发文量
130
审稿时长
28 days
期刊介绍: Peptides is an international journal presenting original contributions on the biochemistry, physiology and pharmacology of biological active peptides, as well as their functions that relate to gastroenterology, endocrinology, and behavioral effects. Peptides emphasizes all aspects of high profile peptide research in mammals and non-mammalian vertebrates. Special consideration can be given to plants and invertebrates. Submission of articles with clinical relevance is particularly encouraged.
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