Evidence Synthesis and Mechanism Analysis of Quercetin Treatment for Atherosclerosis: A Preclinical Systematic Review and Meta-Analysis

Atherosclerosis seriously endangers human health. Quercetin has drawn attention for its potential anti-atherosclerotic pharmacological effects. This study aimed to comprehensively assess quercetin's effect and potential mechanism in treating atherosclerosis through a systematic review and meta-analysis. Preclinical studies published before 20 January 2025 were searched for in databases including PubMed, Embase, Web of Science, CNKI, Wanfang, and VIP. The CAMARADES list was used to assess the quality of the included studies. Stata 12 was applied for overall effect, sensitivity, subgroup, and publication bias analyses. Time-dose interval analyses were conducted to explore how quercetin dose and dosing cycle affect intervention effects. Finally, trial sequential analyses were performed using TSA 0.9 software. A total of 22 studies involving 421 animals were included, with a mean methodological quality score of 7.73/10. Meta-analysis showed that relative to the control group, quercetin reduced aortic plaque area, adjusted lipids (lowered TC, TG, and LDL-C and raised HDL-C), downregulated adhesion factors (e.g., VCAM-1) and pro-inflammatory factors (e.g., IL-1β and IL-6), upregulated anti-inflammatory factor IL-10 and antioxidant enzymes (SOD, CAT) while decreasing MDA content, and regulated atherosclerosis-related targets (e.g., LXRα, SIRT1, and mTOR). Subgroup analyses found model establishment time and quercetin administration time affected aortic lesion areas, TC, and TG. Time-dose analysis indicated quercetin had better ameliorative effects on atherosclerosis at 25-100 mg/kg with an 8-10-week intervention. Quercetin significantly improves atherosclerosis and inhibits its occurrence and progression through multiple pathways, such as regulating lipid metabolism, anti-inflammatory effects, and counteracting oxidative stress. Based on current evidence, quercetin is a potential therapeutic agent for treating atherosclerosis.