Quillaic acid and echinocystic acid attenuate atherosclerosis: evidence from in vitro and in vivo studies

Background Atherosclerosis (AS) is an inflammatory disease characterized by the formation of lipid-laden lesions in arterial walls. Quillaic acid (QA) and echinocystic acid (EA) are natural pentacyclic triterpenes with diverse biological activities. However, whether QA and EA can ameliorate AS has not been reported. Methods In this study, we first investigated the effects of QA and EA in reducing foam cell accumulation and inflammation in vitro . Then, the therapeutic effects of QA and EA (i.p., 5 mg/kg) were evaluated in ApoE knockout (ApoE -/- ) mice fed a high-fat/high-cholesterol diet. Results In vitro experiments demonstrated that both QA and EA suppressed oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation by inhibiting cholesterol uptake and also inhibited lipopolysaccharide (LPS)-induced inflammatory responses. In high-fat/high-cholesterol diet-fed ApoE -/- mice, QA or EA treatment significantly reduced serum lipid levels, decreased inflammatory factor release, and attenuated atherosclerotic plaque formation. At the tested dose, EA showed slightly better anti-inflammatory and plaque-reducing effects than QA. Transcriptomic profiling revealed enrichment of genes associated with “Cell adhesion molecules” and immune response pathways in the aorta of QA-treated mice. For EA, enrichment was observed for genes involved in “Circadian rhythms” in both liver and aorta, as well as genes related to “Vascular smooth muscle contraction” and the “cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway” in aortic tissues. Real-time quantitative PCR (qPCR) analysis confirmed altered expression of selected circadian rhythm-related genes in the liver of EA- and QA-treated mice and in ox-LDL-induced foam cells. EA also increased cGMP levels in these foam cells. Conclusions This study provides the first evidence for the anti-atherosclerotic effects of QA and EA and offers new insights into the potential of natural products for the treatment of cardiovascular diseases.