Ethyl acetate extract of sappanwood alleviates experimental atherosclerosis in rats through changes in FGF21 and SREBP-2 expression.

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.