Hwang Jin-Taek, Choi Eunji, Choi Hyo-Kyoung, Park Jae-Ho, Chung Min-Yu
Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Korea.
Department of Food Biotechnology, Korea University of Science & Technology, Daejeon 34113, Korea.
Foods. 2021 Feb 12;10(2):408. doi: 10.3390/foods10020408.
The objective of the present study was to investigate the mechanism by which capsella bursa-pastoris ethanol extract (CBE), containing 17.5 milligrams of icaritin per kilogram of the extract, and icaritin, mediate hypocholesterolemic activity via the low-density lipoprotein receptor (LDLR) and pro-protein convertase subtilisin/kexin type 9 (PCSK9) in obese mice and HepG2 cells. CBE significantly attenuated serum total and LDL cholesterol levels in obese mice, which was associated with significantly decreased PCSK9 gene expression. HepG2 cells were cultured using delipidated serum (DLPS), and CBE significantly reduced PCSK9 and maintained the LDLR level. CBE co-treatment with rosuvastatin attenuated statin-mediated PCSK9 expression, and further increased LDLR. The icaritin contained in CBE decreased intracellular PCSK9 and LDLR levels by suppressing transcription factors SREBP2 and HNF-1α. Icaritin also significantly suppressed the extracellular PCSK9 level, which likely contributed to post-translational stabilization of LDLR in the HepG2 cells. PCSK9 inhibition by CBE is actively attributed to icaritin, and the use of CBE and icaritin could be an alternative therapeutic approach in the treatment of hypercholesterolemia.
本研究的目的是探究荠菜乙醇提取物（CBE，每千克提取物含17.5毫克淫羊藿素）和淫羊藿素通过低密度脂蛋白受体（LDLR）和前蛋白转化酶枯草溶菌素/克新9型（PCSK9）介导肥胖小鼠和HepG2细胞降胆固醇活性的机制。CBE显著降低了肥胖小鼠的血清总胆固醇和低密度脂蛋白胆固醇水平，这与PCSK9基因表达显著降低有关。使用脱脂血清（DLPS）培养HepG2细胞，CBE显著降低了PCSK9并维持了LDLR水平。CBE与瑞舒伐他汀联合治疗减弱了他汀类药物介导的PCSK9表达，并进一步增加了LDLR。CBE中含有的淫羊藿素通过抑制转录因子SREBP2和HNF-1α降低细胞内PCSK9和LDLR水平。淫羊藿素还显著抑制细胞外PCSK9水平，这可能有助于HepG2细胞中LDLR的翻译后稳定。CBE对PCSK9的抑制作用主要归因于淫羊藿素，使用CBE和淫羊藿素可能是治疗高胆固醇血症的一种替代治疗方法。
