天麻素通过抑制HNF-1α和激活FoxO3a来调节PCSK9/LDLR信号通路，从而减轻高胆固醇血症

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-04-18 DOI:10.1016/j.phymed.2025.156778

Yaowen Zhang , Lan Han , Qiyuan Ning , Xixi Zhang , Menglian Zhang , Jinyong Peng , Hao Chen , Zhiwei Zhao , Dandan Wang

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引用次数: 0

摘要

背景高胆固醇血症是心血管疾病（CVDs）的主要病因。天麻素（Gastrodin，Gas）是天麻的主要活性成分，具有降血脂和抗炎特性，可用于治疗心血管疾病。然而，其降脂功效的内在机制仍有待阐明。PCSK9/LDLR信号通路是调节胆固醇代谢的关键信号通路。目的本研究阐明了Gas是否对高胆固醇血症有抑制作用，以及这种作用是否与PCSK9/LDLR信号通路的调节有关。结果 Gas对高脂饮食小鼠的高胆固醇血症有很强的治疗作用。此外，Gas 还可减轻高密度脂蛋白胆固醇血症诱导的肝脏脂质积累和肝损伤。从机理上讲，Gas 通过抑制 JAK2/STAT3 信号通路来抑制 HNF-1α 并促进 FoxO3a，从而降低 PCSK9 的表达。总之，我们的数据为 Gas 预防和治疗高脂血症提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Gastrodin attenuates hypercholesterolaemia through regulating the PCSK9/LDLR signalling pathway by suppressing HNF-1α and activating FoxO3a

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Gastrodin attenuates hypercholesterolaemia through regulating the PCSK9/LDLR signalling pathway by suppressing HNF-1α and activating FoxO3a

Background

Hypercholesterolaemia is a prevalent etiological factor of cardiovascular diseases (CVDs). Gastrodin (Gas), the paramount active constituent in Gastrodia elata Bl., has lipid-lowering and anti-inflammatory properties for the treatment of CVDs. Nevertheless, the underlying mechanism responsible for hypolipidemic efficacy remains to be elucidated. The signalling pathwayof PCSK9/LDLR is a key signalling pathway that regulates cholesterol metabolism.

Purpose

This investigation elucidated whether Gas has an inhibitory effect on hypercholesterolaemia and whether this effect is associated with the regulation of the PCSK9/LDLR signalling pathway.

Methods

We induced hypercholesterolaemia of mice by feeding them a high-fat diet (HFD) for 12 weeks to analyse the therapeutic effects and related pathways of Gas in vivo. In vitro, western blotting, qRT-PCR, molecular docking, and transfection were employed to verify the molecular mechanism of action of Gas in the treatment of hypercholesterolaemia.

Results

Gas exhibited potent therapeutic effects against hypercholesterolaemia in HFD mice. Moreover, the HFD-induced hepatic lipid accumulation and liver damage were attenuated by Gas. Mechanistically, Gas decreased the expression of PCSK9 via inhibiting the JAK2/STAT3 signalling pathway to suppress HNF-1α and promote FoxO3a. In addition, Gas increased LDLR transcription via SREBP2 activation.

Conclusion

Collectively, our data provide new insights into the prevention and treatment of hyperlipidaemia by Gas.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.