Anti-atherosclerotic effects of Allium hookeri and its mechanism in high fat/high cholesterol-induced obese C57BL/6 mice

Background: Atherosclerosis is a chronic inflammatory disease characterized by plaque accumulation and narrowing of blood vessels. Dietary substances may help to prevent atherosclerosis by modulating lipid metabolism and inflammation. Allium hookeri (A. hookeri), a medicinal herb used in Southeast Asia, exhibits antioxidant and antidiabetic activities. Objective: This study evaluated the protective effects of A. hookeri water extract (AHWE) against atherosclerosis in C57BL/6 mice fed a high-fat/high-cholesterol diet (HFCD) (60% kcal from fat plus 1% cholesterol; HFCD) for 13 weeks. Design: Four-week-old male C57BL/6 mice were divided into four groups (n = 10/group): control (CON), HFCD, HFCD + AHWE 300 mg/kg/day, and HFCD + AHWE 500 mg/kg/day. Following 12 weeks of dietary intervention, the mice were sacrificed at 17 weeks of age. Body and organ weights, serum parameters, histological changes, and the expression of proteins and genes involved in lipid metabolism and inflammation were analyzed. The immunomodulatory effects of AHWE were evaluated using regulatory T cells (Tregs). Results: AHWE supplementation at 500 mg/kg/day reduced body weight gain, liver and adipose tissue weights, and serum levels of alanine aminotransferase, aspartate aminotransferase, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and insulin, while increasing high-density lipoprotein cholesterol levels and reducing the atherogenic index in HFCD. AHWE alleviated hepatic lipid accumulation and aortic intimal thickening. Mechanistically, AHWE upregulated peroxisome proliferator-activated receptor gamma, liver X receptor alpha, and ATP-binding cassette transporter A1 expression and downregulated CD36, SR-A1, and LOX-1. In addition, AHWE promoted AMP-activated protein kinase activation, inhibited mechanistic target of rapamycin phosphorylation, and suppressed inflammatory responses by reducing nuclear factor-kappa B, cyclooxygenase-2, tumor necrosis factor-alpha, and interleukin-6 expression. AHWE increased Treg populations, and IL-10 secretion, while ex vivo analysis confirmed its anti-inflammatory effects. Moreover, AHWE inhibited H3K9 and H3K27 acetylation. Conclusion: These findings suggest that AHWE at 500 mg/kg/day may alleviate atherosclerosis by regulating lipid metabolism, inflammation, Treg-mediated immune balance, and histone acetylation.