The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells.
The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells.
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DOI：
10.3390/foods10020408
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发表时间：
2021-02-12
期刊：
影响因子：
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通讯作者：
Chung MY
中科院分区：
文献类型：
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作者：
Hwang JT;Choi E;Choi HK;Park JH;Chung MY
本研究的目的是探讨荠菜乙醇提取物（CBE），每公斤提取物中含有17.5毫克淫羊藿苷，淫羊藿苷，介导的机制，通过低密度脂蛋白受体（LDLR）和前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK 9）在肥胖小鼠和HepG2细胞的降胆固醇活性。CBE显著降低了肥胖小鼠的血清总胆固醇和LDL胆固醇水平，这与PCSK9基因表达的显著降低有关。HepG2细胞使用脱脂血清（DLPS）培养，CBE显著降低PCSK 9并维持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PCSK 9表达，并进一步增加了LDLR。CBE中含有的淫羊藿苷通过抑制转录因子SREBP 2和HNF-1 α降低细胞内PCSK 9和LDLR水平。淫羊藿苷还显著抑制细胞外PCSK 9水平，这可能有助于HepG2细胞中LDLR的翻译后稳定。CBE对PCSK 9的抑制作用主要归因于淫羊藿苷，CBE和淫羊藿苷的使用可能是治疗高胆固醇血症的替代治疗方法。
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.