Mult-omics analysis reveals the lipid-lowering effects of sea buckthorn and milk thistle solid beverage in hyperlipidemic rats

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-05-29 DOI:10.1016/j.phymed.2025.156920

Yuwei Bai , Jianglong Li , Xueqian Wu , Mei Zhang , Yaping Zhang , Ping Chen , Jiajing Ma , Suzhen Zhang , Haicheng Zhang , Xiangjun Li , Zhigang Yang

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引用次数: 0

Abstract

Background

Hyperlipidemia is a common metabolic disorder and a risk factor for cardiovascular disease. The traditional medicine herb, Hippophae rhamnoides L., known as sea buckthorn, has anti-obesity and lipid-lowering effects, while Silybum marianum (L.) Gaertn, known as milk thistle, has hepatoprotective properties and exhibits antioxidant effects.

Purpose

To evaluate the effect of sea buckthorn and milk thistle solid beverage (H-S solid beverage) in alleviating hyperlipidemia in rats and explore the underlying mechanisms by analyzing plasma and liver metabolomics, lipidomics, and liver transcriptomics.

Methods

A hyperlipidemic rat model was established after 2 weeks of high-fat diet (HFD) feeding in Sprague Dawley rats. The administered doses of H-S solid beverage were 0.30 g/kg/d, 0.15 g/kg/d and 0.075 g/kg/d. Serum biochemical parameter detection, histopathological section analysis, untargeted plasma and liver metabolomics, lipidomics, and liver transcriptomics were performed to determine the therapeutic effects of H-S solid beverage and predict the related pathways in rats with hyperlipidemia. Changes in genes and proteins related to lipid metabolism were detected using real-time quantitative polymerase chain reaction and western blotting.

Results

Eighty-nine components were identified in H-S solid beverage using ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry, with flavonoids being the major constituents. The H-S solid beverage significantly reduced body weight, liver index, body fat percentage, lipid accumulation, and liver injury in HFD-fed rats. Fatty acids (FA), bile acid, phosphatidyl ethanolamine, phosphatidylcholine, triglyceride, cholesterol ester, diglyceride and phosphatidylinositol levels were significantly altered in the liver and plasma. Moreover, the transcriptomic analysis suggested that H-S solid beverage significantly altered the hepatic gene expression of cholesterol synthesis (Pdk4, Hmgcs1, and Dhcr24), lipogenesis (Scd, Angptl4, and Angptl8), and FA β-oxidation (Cpt1α, Pparδ, Acsl, Pgc-1α, and Pla2g2d).

Conclusion

The solid beverage of sea buckthorn and milk thistle was firstly demonstrated to ameliorate HFD-induced hyperlipidemia. The lipid-lowering and hepatoprotective effects of H-S solid beverage significantly regulated cholesterol synthesis and de novo lipogenesis, as well as FA β-oxidation. In summary, this study highlights the potential of H-S solid beverages for the treatment of hyperlipidemia.

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多组学分析揭示了沙棘和水飞蓟固体饮料对高脂血症大鼠的降脂作用

背景：高脂血症是一种常见的代谢性疾病，也是心血管疾病的危险因素。传统草药沙棘（Hippophae rhamnoides L.，又称沙棘）具有抗肥胖和降脂作用，而水飞蓟（ilybum marianum， L.）牛乳蓟，俗称水飞蓟，具有保护肝脏和抗氧化作用。目的通过血浆和肝脏代谢组学、脂质组学和肝脏转录组学分析，评价沙棘水飞蓟固体饮料（H-S固体饮料）对大鼠高脂血症的缓解作用，并探讨其作用机制。方法采用高脂饲料喂养2周后建立高脂血症大鼠模型。H-S固体饮料给药剂量分别为0.30 g/kg/d、0.15 g/kg/d和0.075 g/kg/d。通过血清生化参数检测、组织病理切片分析、非靶向血浆和肝脏代谢组学、脂质组学、肝脏转录组学等方法，确定H-S固体饮料对高脂血症大鼠的治疗作用，并预测相关通路。采用实时定量聚合酶链反应和western blotting检测脂质代谢相关基因和蛋白的变化。结果采用超高效液相色谱-四极杆飞行时间质谱联用技术，鉴定出H-S固体饮料中89种成分，主要成分为黄酮类化合物。H-S固体饮料显著降低饲喂hfd大鼠的体重、肝脏指数、体脂率、脂质积累和肝损伤。肝脏和血浆中脂肪酸（FA）、胆汁酸、磷脂酰乙醇胺、磷脂酰胆碱、甘油三酯、胆固醇酯、二甘油三酯和磷脂酰肌醇水平显著改变。此外，转录组学分析表明，H-S固体饮料显著改变了肝脏胆固醇合成基因（Pdk4、Hmgcs1和Dhcr24）、脂肪生成基因（Scd、Angptl4和Angptl8）和FA β氧化基因（Cpt1α、Pparδ、Acsl、Pgc-1α和Pla2g2d）的表达。结论首次证实沙棘水飞蓟固体饮料对hfd诱导的高脂血症有改善作用。H-S固体饮料的降脂和保肝作用显著调节胆固醇合成和新生脂肪生成，以及FA β-氧化。总之，这项研究强调了H-S固体饮料治疗高脂血症的潜力。

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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.