Inhibitory effect of trans-tiliroside on very low-density lipoprotein secretion in HepG2 cells and mouse liver

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines Pub Date : 2023-11-16 DOI:10.1007/s11418-023-01756-0

Akifumi Nagatomo, Mamiko Kohno, Hirosato Kawakami, Yoshiaki Manse, Toshio Morikawa

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引用次数: 0

Abstract

An acylated flavonol glycoside, trans-tiliroside (1), is found in certain parts of different herbs, including the seeds of Rosa canina (Rosaceae). Previous studies on compound 1 have focused on triglyceride (TG) metabolism, including its anti-obesity and intracellular TG reduction effects. In the present study, the effects of compound 1 on cholesterol (CHO) metabolism were investigated using human hepatocellular carcinoma-derived HepG2 cells and mice. Compound 1 decreased CHO secretion in HepG2 cells, which was enhanced by mevalonate in a concentration-dependent manner and decreased the secretion of apoprotein B (apoB)-100, a marker of very low-density lipoprotein (VLDL). Compound 1 also inhibited the activity of microsomal triglyceride transfer proteins, which mediate VLDL formation from cholesterol and triglycerides in the liver. In vivo, compound 1 inhibited the accumulation of Triton WR-1339-induced TG in the blood of fasted mice and maintained low levels of apoB-100. These results suggest that compound 1 inhibits the secretion of CHO as VLDL from the liver and has the potential for use for the prevention of dyslipidemia.

Graphical abstract

Abstract Image

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反式铁力内酯对HepG2细胞和小鼠肝脏极低密度脂蛋白分泌的抑制作用。

一种酰基化的黄酮醇苷，反式tiliroside(1)，存在于不同草药的某些部分，包括Rosa canina(蔷薇科)的种子。以往对化合物1的研究主要集中在甘油三酯(TG)代谢方面，包括其抗肥胖和降低细胞内TG的作用。本研究利用人肝细胞癌源性HepG2细胞和小鼠研究了化合物1对胆固醇(CHO)代谢的影响。化合物1降低HepG2细胞的CHO分泌，甲羟戊酸呈浓度依赖性增强CHO分泌，并降低载脂蛋白B (apoB)-100的分泌，载脂蛋白B是极低密度脂蛋白(VLDL)的标志。化合物1还抑制微粒体甘油三酯转移蛋白的活性，该蛋白介导肝脏中胆固醇和甘油三酯形成VLDL。在体内，化合物1抑制Triton wr -1339诱导的TG在禁食小鼠血液中的积累，并维持低水平的apoB-100。这些结果表明，化合物1可以抑制肝脏以VLDL形式分泌CHO，并有可能用于预防血脂异常。

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.