Ugusman Azizah, Ismail Siti Marjiana, Nor Hisam Nur Syahidah, Hui Chua Kien, Saleh Mohammed S M, Abdul Karim Abdul Kadir, Othman Nur Syakirah, Hamid Adila A, Aminuddin Amilia
Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.
Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia.
Int J Mol Sci. 2024 Feb 28;25(5):2806. doi: 10.3390/ijms25052806.
Angiotensin-converting enzyme (ACE) plays a crucial role in the pathogenesis of hypertension. Roxb., an herb known for its antihypertensive effect, lacks a comprehensive understanding of the mechanism underlying its antihypertensive action. This study aimed to elucidate the antihypertensive mechanism of aqueous extract of leaves (AEPS) via its modulation of the ACE pathway in phorbol 12-myristate-13-acetate (PMA)-induced human umbilical vein endothelial cells (HUVECs). HUVECs were divided into five groups: control, treatment with 200 µg/mL AEPS, induction 200 nM PMA, concomitant treatment with 200 nM PMA and 200 µg/mL AEPS, and treatment with 200 nM PMA and 0.06 μM captopril. Subsequently, ACE mRNA expression, protein level and activity, angiotensin II (Ang II) levels, and angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) mRNA expression in HUVECs were determined. AEPS successfully inhibited ACE mRNA expression, protein and activity, and angiotensin II levels in PMA-induced HUVECs. Additionally, AT1R expression was downregulated, whereas AT2R expression was upregulated. In conclusion, AEPS reduces the levels of ACE mRNA, protein and activity, Ang II, and AT1R expression in PMA-induced HUVECs. Thus, AEPS has the potential to be developed as an ACE inhibitor in the future.
血管紧张素转换酶（ACE）在高血压发病机制中起关键作用。萝芙木是一种以其降压作用而闻名的草药，但其降压作用的潜在机制尚缺乏全面了解。本研究旨在通过在佛波醇12 - 肉豆蔻酸酯 - 13 - 乙酸酯（PMA）诱导的人脐静脉内皮细胞（HUVECs）中调节ACE途径，阐明萝芙木叶水提取物（AEPS）的降压机制。将HUVECs分为五组：对照组、用200μg/mL AEPS处理组、用200 nM PMA诱导组、用200 nM PMA和200μg/mL AEPS联合处理组以及用200 nM PMA和0.06μM卡托普利处理组。随后，测定HUVECs中ACE mRNA表达、蛋白水平和活性、血管紧张素II（Ang II）水平以及血管紧张素II 1型受体（AT1R）和血管紧张素II 2型受体（AT2R）mRNA表达。AEPS成功抑制了PMA诱导的HUVECs中ACE mRNA表达、蛋白和活性以及血管紧张素II水平。此外，AT1R表达下调，而AT2R表达上调。总之，AEPS降低了PMA诱导的HUVECs中ACE mRNA、蛋白和活性、Ang II以及AT1R表达水平。因此，AEPS未来有潜力被开发为一种ACE抑制剂。
