School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China,
School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
Pharmacology. 2022;107(9-10):495-509. doi: 10.1159/000525218. Epub 2022 Jun 9.
The increased migration of vascular smooth muscle cells (VSMCs) is an essential pathological factor in the early development of atherosclerosis. Beta-sitosterol (BS), a natural phytosterol abundant in plant seeds, exhibits various bioactivities, including cardioprotective effects. However, its effects on VSMC migration and underlying mechanisms remain to be explored.
BS inhibited the proliferation and migration of angiotensin II-induced A7r5 cells and reduced intracellular oxidative stress. Targets related to VSMC migration and the targets of BS were screened, cross-referenced, and analyzed by network pharmacology combined with molecular docking technology. The identified targets were verified at the protein and gene levels using Western blotting and quantitative PCR, respectively. BS was observed to activate peroxisome proliferator-activated receptor-γ (PPARG) and adenosine 5'-monophosphate-activated protein kinase (AMPK) and negatively regulate mammalian target of rapamycin (mTOR) expression. Furthermore, a PPARG inhibitor reversed the BS-induced activation of AMPK and mTOR.
This study indicated that regulation of the PPARG/AMPK/mTOR signaling pathway could potentially contribute to the inhibitory effects of BS on angiotensin II-induced VSMC migration.
血管平滑肌细胞（VSMCs）的迁移增加是动脉粥样硬化早期发展的一个重要病理因素。β-谷甾醇（BS）是植物种子中丰富的天然植物固醇，具有多种生物活性，包括心脏保护作用。然而，其对 VSMC 迁移的影响及其潜在机制仍有待探索。
BS 抑制血管紧张素 II 诱导的 A7r5 细胞的增殖和迁移，并降低细胞内氧化应激。通过网络药理学结合分子对接技术筛选、交叉参考和分析与 VSMC 迁移相关的靶点和 BS 的靶点。使用 Western blot 和定量 PCR 分别在蛋白质和基因水平上验证了 BS 对靶点的作用。结果表明，BS 可激活过氧化物酶体增殖物激活受体-γ（PPARG）和腺苷 5'-单磷酸激活蛋白激酶（AMPK），并负调控哺乳动物雷帕霉素靶蛋白（mTOR）的表达。此外，PPARG 抑制剂可逆转 BS 诱导的 AMPK 和 mTOR 的激活。
本研究表明，BS 通过调节 PPARG/AMPK/mTOR 信号通路，可能对血管紧张素 II 诱导的 VSMC 迁移具有抑制作用。
