Huan Pengtao, Sun Liping, Chen Shupeng, Zhong Yujie, Zhuang Yongliang
Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, China.
Yunnan Technology Innovation Center of Woody Oil, Kunming, China.
J Food Sci. 2025 Jan;90(1):e17617. doi: 10.1111/1750-3841.17617. Epub 2025 Jan 9.
Hypertension is a major risk factor for many cardiovascular diseases, which can lead to kidney and heart disease, stroke, and premature death. Inhibiting angiotensin-converting enzyme (ACE) activity is an effective method to relieve hypertension. Previously, we screened an active peptide KYPHVF (KF6) from Boletus griseus-Hypomyces chrysospermus with excellent ACE inhibitory activity. This study further evaluated the antihypertensive activity of the KF6 in vivo. KF6 at 10 mg/kg and Captopril (CAP, a positive control) at 10 mg/kg were administrated to spontaneous hypertensive rats (SHRs) for 5 weeks. The results demonstrated that KF6 effectively lowered both diastolic blood pressure (DBP) and systolic blood pressure (SBP), and decreased ACE, AGT, ALD, and ANG II levels in the serum of SHRs. Furthermore, both cardiac and renal injury of SHRs were ameliorated by KF6 through inhibiting fibrosis, inflammation, and oxidative stress. Moreover, KF6 inhibited ACE-ANG II-AT1 axis while activating the ACE2-Ang (1-7)-MAS1L pathway, two mutually antagonistic axes of RAAS, in the kidney and heart of SHRs. Additionally, KF6 improved intestinal microbiota composition, mainly by increasing the abundance of Prevotella and Phascolarctobacterium while decreasing the abundance of Alistipes, Clostridium_IV, Nosocomiicoccus, and Allobaculum. Overall, KF6 is a promising ACE inhibitory peptide for lowering blood pressure and mitigating hypertension-related cardiac and renal damage. The protective effect of KF6 against hypertension is attributed to its ability to modulate RAAS and intestinal microbiota.
高血压是许多心血管疾病的主要危险因素，可导致肾病、心脏病、中风和过早死亡。抑制血管紧张素转换酶（ACE）活性是缓解高血压的有效方法。此前，我们从灰褐牛肝菌-金黄被孢霉中筛选出一种具有优异ACE抑制活性的活性肽KYPHVF（KF6）。本研究进一步评估了KF6在体内的降压活性。将10mg/kg的KF6和10mg/kg的卡托普利（CAP，阳性对照）给予自发性高血压大鼠（SHR）5周。结果表明，KF6有效降低了舒张压（DBP）和收缩压（SBP），并降低了SHR血清中ACE、AGT、ALD和ANG II的水平。此外，KF6通过抑制纤维化、炎症和氧化应激改善了SHR的心脏和肾脏损伤。此外，KF6在SHR的肾脏和心脏中抑制了ACE-ANG II-AT1轴，同时激活了RAAS的两个相互拮抗的轴，即ACE2-Ang（1-7）-MAS1L途径。此外，KF6改善了肠道微生物群组成，主要是通过增加普雷沃氏菌属和考拉杆菌属的丰度，同时降低阿里斯杆菌属、梭菌属IV、嗜麦芽窄食单胞菌属和别氏菌属的丰度。总体而言，KF6是一种有前景的ACE抑制肽，可降低血压并减轻高血压相关的心脏和肾脏损伤。KF6对高血压的保护作用归因于其调节RAAS和肠道微生物群的能力。
