Cancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine of Qingdao University, Qingdao, China; Qingdao Cancer Institute, Qingdao, China.
Cancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine of Qingdao University, Qingdao, China; Qingdao Cancer Institute, Qingdao, China.
Bioorg Med Chem Lett. 2022 Nov 1;75:128974. doi: 10.1016/j.bmcl.2022.128974. Epub 2022 Sep 5.
Emodin (EM) is one of the active components of the traditional Chinese medicine rhubarb, and there is evidence of its hypolipidemic activity, though the exact mechanism is unknown. NPC1L1 is a key protein in human cholesterol uptake that is primarily expressed in hepatocytes and gastrointestinal epithelial cells. Our findings suggest that rhodopsin inhibits cellular cholesterol uptake by influencing NPC1L1 cholesterol transport. The results showed that NBD-cholesterol uptake in human HepG2 cells was 27 %, 31.3 %, 33.6 %, 41.6 %, and 52.6 % of control after treatment with 100, 75, 50, 25, and 12.5 % M EM, respectively, compared to 50 % for 100 M Ezetimibe. Kinetic studies revealed that EM inhibited cellular uptake of cholesterol through anti-competitive inhibition. Furthermore, using confocal fluorescence quantification, we discovered that after cholesterol deprivation treatment reintroduced cholesterol supply, cholesterol uptake was significantly higher in HepG2 cells highly expressing NPC1L1 than in U2OS cells with low NPC1L1 expression. As a result, we hypothesize that EM may inhibit cholesterol uptake via NPC1L1 in human hepatocytes in an anti-competitive manner. Overall, as a dietary supplement or lipid-modifying drug, EM has the potential to lower cholesterol.
大黄素（EM）是传统中药大黄的活性成分之一，有降血脂活性的证据，但确切机制尚不清楚。NPC1L1 是人体胆固醇摄取的关键蛋白，主要在肝细胞和胃肠道上皮细胞中表达。我们的研究结果表明，视黄醇通过影响 NPC1L1 胆固醇转运来抑制细胞内胆固醇摄取。结果表明，用 100、75、50、25 和 12.5% M EM 处理人 HepG2 细胞后，NBD-胆固醇摄取分别为对照的 27%、31.3%、33.6%、41.6%和 52.6%，而 100 M 依泽替米贝则为 50%。动力学研究表明，EM 通过反竞争性抑制抑制细胞内胆固醇摄取。此外，通过共聚焦荧光定量，我们发现在用胆固醇剥夺处理再引入胆固醇供应后，高表达 NPC1L1 的 HepG2 细胞中的胆固醇摄取明显高于 NPC1L1 低表达的 U2OS 细胞。因此，我们假设 EM 可能通过 NPC1L1 在人肝细胞中以反竞争性方式抑制胆固醇摄取。总的来说，作为膳食补充剂或调脂药物，EM 有可能降低胆固醇。
