Anti-adipogenic and Lipid-modulating Effect of Tanshinone IIA-Enriched Salvia miltiorrhiza Extract in 3T3-L1 Cells and a P-407-induced Dyslipidemic Mouse Model

Background: This study aimed to evaluate the anti-adipogenic and lipid-modulating effects of tanshinone IIA (Tan IIA)-enriched Salvia miltiorrhiza extract (SM-CPE) prepared using cloud-point extraction (CPE), an eco-friendly method designed to enhance the yield of hydrophobic bioactive compounds. Methods and Results: High-performance liquid chromatography confirmed that SM-CPE contained approximately 35 times more Tan IIA than the conventional water extract (SMW). In 3T3-L1 preadipocytes, Tan IIA showed cytotoxicity at concentrations ≥ 5 μM, while SMW was non-cytotoxic up to 200 ㎍/㎖. In contrast, SM-CPE began to show cytotoxicity from 200 ㎍/㎖, likely due to the high concentration of Tan IIA. An adipogenesis assay revealed that SM-CPE inhibited lipid accumulation by 17.6% at 100 ㎍/㎖ and by 81.0% inhibition at 200 ㎍/㎖. In comparison, SMW showed relatively weak inhibition (19.9% at 200 ㎍/㎖), while Tan IIA exhibited a dose-dependent inhibition, reaching 64.4% at 20 μM. In a P-407-induced dyslipidemic mouse model, 14 days of oral administration of SM-CPE significantly reduced serum triglycerides by 54.2%, which was more than double that of SMW (23.9%) and similar to that of Tan IIA (65.6%). SM-CPE also lowered total cholesterol and low-density lipoprotein levels, whereas HDL levels increased slightly, although not statistically significant. Conclusions: SM-CPE demonstrated superior anti-adipogenic and lipid-lowering effects compared with SMW and Tan IIA, supporting its potential as a natural agent for treating obesity-related metabolic disorders, such as dyslipidemia. CPE offers a practical strategy for enhancing the functional efficacy of herbal extracts by concentrating lipophilic bioactive compounds such as Tan IIA.