Asiaticoside alleviates atherosclerosis progression by suppressing RhoF–NF-κB/MAPK signaling and inflammation in macrophages

作者：Junlu Wang, Lingli Lei, Shasha Wang, Yuanyuan Sun · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.157137 · 被引用次数：12 · 研究领域：Medicinal Plants and Neuroprotection、Traditional Chinese Medicine Analysis、Phytochemicals and Medicinal Plants

BACKGROUND: Asiaticoside (AT), a triterpenoid derived from Centella asiatica, has long been recognized for its anti-inflammatory properties. Its potential to ameliorate atherosclerosis (AS), a chronic inflammatory disease, positions it as a promising therapeutic agent, although its underlying mechanisms remain to be fully elucidated. PURPOSE: This study aimed to evaluate the anti-atherosclerotic effects of AT and elucidate the molecular mechanisms underlying its therapeutic actions in AS. STUDY DESIGN: The research included in vivo animal experiments, in vitro cellular studies, and target exploration and validation. METHODS: mice fed a chow diet served as controls. Network pharmacology and RNA sequencing (RNA-Seq) of aortas identified dysregulated target genes and pathways. Oxidized low-density lipoprotein (Ox-LDL)-stimulated peritoneal macrophages were used for in vitro studies. Molecular docking, dynamics simulations, surface plasmon resonance (SPR) arrays, Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence were conducted to elucidate AT's anti-inflammatory mechanisms. RESULTS: mice by reducing macrophage infiltration in plaques in vivo and suppressing inflammation in ox-LDL-stimulated macrophages in vitro. Integrated network pharmacology and RNA-Seq analyses identified Ras homolog family member F (RhoF) as a key target, with significantly elevated RhoF expression in AS plaques and macrophages, which was markedly reduced by AT treatment. Mechanistical...