Graduate Institute of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan.
Graduate Institute of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; Department of Chinese Medicine, Show Chwan Memorial Hospital, Changhua, 50008, Taiwan.
J Ethnopharmacol. 2020 May 23;254:112724. doi: 10.1016/j.jep.2020.112724. Epub 2020 Feb 28.
Hypertension is one of the common chronic health problems in the world. Astragalus membranaceus root (AM), also known as Huangqi, is a popular medicinal herb traditionally used to reinforce vital energy and modulate hypertension.
This study was to reveal the anti-hypertensive activities and mechanisms of AM in spontaneously hypertensive rats (SHRs). Moreover, the presence of bioactive components in AM was further identified.
We analyzed the effects of aqueous extract of AM (AME) on the regulation of blood pressure and angiotensin converting enzyme (ACE), the major target of anti-hypertensive drugs. Proteomic, bioinformatics, and docking analyses were performed to identify the anti-hypertensive bioactive peptides in AME.
Our data showed that AME inhibited ACE activities in a dose-dependent manner, with an IC of 1.85 ± 0.01 μg/ml. In comparison with mock, oral administration of AME reduced systolic blood pressure (SBP) levels in SHRs, and the level of SBP was decreased by 22.33 ± 3.61 mmHg at 200 mg/kg AME. Proteomic analysis identified that an abundant 152-amino-acid putative protein kinase fragment accounted for approximately 11.7% of protein spots in AME. AM-1 (LVPPHA), a gastrointestinal enzyme-resistant peptide cleaved from putative protein kinase fragment, inhibited ACE activities, with an IC value of 414.88 ± 41.88 μM. Moreover, oral administration of AM-1 significantly decreased SBP levels by 42 ± 2.65 mmHg at 10 μmol/kg. Docking analysis further showed that AM-1 docked into the active site channel of ACE and interacted with Ala-354 in the active site pocket of ACE.
the ACE inhibitory effect of AM and the presence of ACE inhibitory phytopeptide in AME supported the ethnomedical use of AM on hypertension.
高血压是世界上常见的慢性健康问题之一。黄芪（Astragalus membranaceus root，AM），又称黄芪，是一种常用的草药，传统上用于增强生命力和调节高血压。
本研究旨在揭示黄芪水提物（AME）在自发性高血压大鼠（SHR）中的抗高血压活性和机制。此外，进一步鉴定 AM 中的生物活性成分。
我们分析了 AM 水提物（AME）对血压和血管紧张素转换酶（ACE）调节的影响，ACE 是抗高血压药物的主要靶点。进行了蛋白质组学、生物信息学和对接分析，以鉴定 AME 中的抗高血压生物活性肽。
我们的数据表明，AME 以剂量依赖的方式抑制 ACE 活性，IC 为 1.85±0.01μg/ml。与模拟组相比，AME 口服给药可降低 SHR 的收缩压（SBP）水平，200mg/kg AME 时 SBP 水平降低 22.33±3.61mmHg。蛋白质组学分析鉴定出一种丰富的 152 个氨基酸的假定蛋白激酶片段，占 AME 中蛋白质斑点的约 11.7%。从假定蛋白激酶片段中切割得到的一种胃肠道酶抗性肽 AM-1（LVPPHA）抑制 ACE 活性，IC 值为 414.88±41.88μM。此外，10μmol/kg AM-1 口服给药可使 SBP 水平显著降低 42±2.65mmHg。对接分析进一步表明，AM-1 与 ACE 的活性位点通道结合，并与 ACE 活性口袋中的 Ala-354 相互作用。
AM 的 ACE 抑制作用以及 AME 中存在 ACE 抑制植物肽支持 AM 在高血压中的传统医学用途。
