Introduction: 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.
Method and result: 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.
Conclusion: 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.
Keywords: Beta-sitosterol; Migration; Network pharmacology analysis; Peroxisome proliferator-activated receptor/adenosine 5’-monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathway; Vascular smooth muscle cells.
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