Ethyl acetate extract of sappanwood alleviates experimental atherosclerosis in rats through changes in FGF21 and...

Sappanwood extract shows promising effects against atherosclerosis. The fibroblast growth factor 21 (FGF21) and sterol regulatory element-binding protein 2 (SREBP2) are involved in atherosclerosis development. This study aimed to examine whether sappanwood ethyl acetate extract (SEAE) alleviates experimental atherosclerosis in rats through FGF21/SREBP-2 signaling. Rats were randomized to six groups (n=10/group): blank control, model, simvastatin (positive control, 4.2 mg/kg/d), and SEAE high-, medium-, and low-dose (2.30, 1.15, and 0.575 g/kg/d, respectively). The high-fat- and vitamin D3-induced rodent model of atherosclerosis was created (except in the blank control group). Aorta and liver underwent histopathologic examination. SREPB-2 and FGF21 expression levels were examined by real-time RT-PCR and western blot. Compared with the blank control group, the model group showed aortic and hepatic histopathology compatible with the development of atherosclerosis due to a high-fat diet. In addition, total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) were elevated (all P<0.05). SREBP2 expression was high, and FGF21 expression was low (both P<0.05). Compared with the model group, SEAE alleviated the changes in liver and aorta by histopathology and decreased total cholesterol, triglycerides, and LDL-C (all P<0.05), especially in the medium-, and high-dose groups. In addition, medium-dose SEAE increased FGF21 levels (mRNA: +296%; protein: +69%; P<0.05) and decreased SREBP2 levels (mRNA: -44%; protein: -77%; P<0.05). Simvastatin, as the positive control, had similar effects to those of SEAE. In conclusion, SEAE improves lipid metabolism and alleviates atherosclerosis through changes in FGF21 and SREBP-2 expression levels.