Abstract

Cynandione A (CA), isolated from ethyl acetate extract of Cynanchum wilfordii (CW), is a bioactive phytochemical that has been found to be beneficial for the treatment of several diseases. Hepatic de novo lipogenesis is one of the main causes of non-alcoholic fatty liver disease (NAFLD), which is thought to be a hepatic manifestation of certain metabolic syndromes. However, it has not yet been reported if CA has any therapeutic value in these diseases. Here, we investigated whether CA can inhibit hepatic lipogenesis induced by liver X receptor α (LXRα) using an in vitro model. We found that the extract and ethyl acetated layer of CW decreased the mRNA levels of sterol regulatory element-binding protein-1c (SREBP-1c), which plays a crucial role in hepatic lipogenesis. Additionally, we observed that CA could suppress the level of SREBP-1c, which was increased using two commercial LXRα agonists, GW3954 and T0901317. Moreover, the enzymes that act downstream of SREBP-1c were also inhibited by CA treatment. To understand the mechanism underlying this effect, the levels of phosphorylated AMP kinase (pAMPK) were measured after CA treatment. Therefore, CA might increase the pAMPK level by inducing phosphorylation of liver kinase B1 (LKB1), which can then convert AMPK to pAMPK. Taken together, we conclude that CA has an alleviative effect on hepatic lipogenesis through the stimulation of the LKB1/AMPK pathway.

Graphical abstract

中文翻译：

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Cynanchum wilfordii 中的 Cynandione A 通过激活 HepG2 细胞中的 LKB1/AMPK 通路来抑制肝脏从头脂肪生成。

摘要

Cynandione A (CA)，从Cynanchum wilfordii的乙酸乙酯提取物中分离出来(CW)，是一种生物活性植物化学物质，已被发现对治疗多种疾病有益。肝脏从头脂肪生成是非酒精性脂肪性肝病 (NAFLD) 的主要原因之一，它被认为是某些代谢综合征的肝脏表现。然而，尚未报道 CA 是否对这些疾病有任何治疗价值。在这里，我们使用体外模型研究了 CA 是否可以抑制由肝脏 X 受体α (LXRα) 诱导的肝脏脂肪生成。我们发现 CW 的提取物和乙酸乙酯层降低了甾醇调节元件结合蛋白-1c (SREBP-1c) 的 mRNA 水平，这在肝脏脂肪生成中起关键作用。此外，我们观察到 CA 可以抑制 SREBP-1c 的水平，使用两种商业 LXRα 激动剂 GW3954 和 T0901317 可以提高 SREBP-1c 的水平。而且，作用于 SREBP-1c 下游的酶也受到 CA 处理的抑制。为了了解这种作用背后的机制，在 CA 处理后测量了磷酸化 AMP 激酶 (pAMPK) 的水平。因此，CA 可能通过诱导肝激酶 B1 (LKB1) 的磷酸化来增加 pAMPK 水平，从而将 AMPK 转化为 pAMPK。总之，我们得出结论，CA 通过刺激 LKB1/AMPK 通路对肝脏脂肪生成具有缓解作用。

图形概要