Stevia rebaudiana root polysaccharide modulates liver metabolism, bile acid, and gut microbiota improving HFD-induced NAFLD: Potential roles of ACSL1 and FADS2

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-03-24 DOI:10.1016/j.phymed.2025.156680

Yulong Bao , Xiaolong Shang , Guangdong Hu , Jiapeng Wang , Chunyan Liu , Qiuyue Lv , Hui Che , Jun Han , Taili Shao , Guodong Wang

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引用次数: 0

Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder characterized by liver lipid accumulation and insulin resistance. However, effective therapeutic drugs for NAFLD are currently unavailable. Stevia rebaudiana root polysaccharides (SRRP) are inulin-type polysaccharides known for their hypoglycemic properties. Despite this, the effects of SRRP on improving NAFLD and the underlying mechanisms remain poorly understood.

Purpose

This study aims to evaluate the potential of SRRP in alleviating NAFLD and to explore its mechanisms of action.

Methods

NAFLD was induced in male C57BL/6 J mice through high-fat diet (HFD) feeding, with subsequent SRRP administration over 8 weeks. Comprehensive assessments included serum biochemical profiling, hepatic histopathological examination, and proinflammatory enzyme activity quantification. Mechanistic investigations employed tripartite analytical approaches: gut microbiota analysis via 16S rRNA sequencing, hepatic metabolomic profiling and bile acid profiling, and validation of transport protein expression through Western blot (WB) techniques.

Results

SRRP administration significantly alleviated NAFLD through reduced serum lipid concentrations, ameliorated inflammatory responses and oxidative stress, and decreased hepatic lipid deposition mechanistically, SRRP improved the structure of the gut microbiota by enhancing the proliferation of beneficial bacterial, including Lactobacillales and Bifidobacteriales, which subsequently elevated circulating Cholic acid (CA) and Chenodeoxycholic acid (CDCA), and improved hepatic lipid metabolites. Notably, KEGG from metabolomics indicated that the linoleic acid pathway might be associated with the improvement in hepatic lipid metabolite levels by SRRP. In Western blot analysis, SRRP significantly upregulated hepatic ACSL1 and FADS2 in NAFLD mice, demonstrating that the alleviation of NAFLD by SRRP may be achieved through the reduction of hepatic lipid accumulation.

Conclusions

SRRP exerts effects on improving NAFLD by modulating the gut microbiota, hepatic metabolites, bile acid levels, and the expression of ACSL1 and FADS2 proteins, providing more scientific evidence and support for the improvement of NAFLD by SRRP.

Abstract Image

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甜叶菊根多糖可调节肝脏代谢、胆汁酸和肠道微生物群，改善高氟脂饮食诱发的非酒精性脂肪肝：ACSL1 和 FADS2 的潜在作用

背景：非酒精性脂肪性肝病（NAFLD）是一种以肝脏脂质积累和胰岛素抵抗为特征的普遍代谢紊乱。然而，目前还没有有效的治疗NAFLD的药物。甜菊糖根多糖（SRRP）是一种以降血糖著称的菊糖型多糖。尽管如此，SRRP对改善NAFLD的作用及其潜在机制仍然知之甚少。目的评价SRRP缓解NAFLD的潜力，并探讨其作用机制。方法采用高脂饲料（HFD）诱导雄性C57BL/ 6j小鼠snafld，并给予SRRP 8周。综合评估包括血清生化分析、肝脏组织病理学检查和促炎酶活性定量。机制研究采用三方分析方法：通过16S rRNA测序分析肠道微生物群，肝脏代谢组学分析和胆汁酸分析，以及通过Western blot （WB）技术验证转运蛋白表达。结果SRRP通过降低血清脂质浓度、改善炎症反应和氧化应激、减少肝脏脂质沉积等机制显著缓解NAFLD， SRRP通过促进乳酸菌和双歧杆菌等有益菌的增殖改善肠道菌群结构，从而提高循环胆酸（CA）和鹅去氧胆酸（CDCA）水平。改善肝脏脂质代谢。值得注意的是，代谢组学的KEGG表明，亚油酸途径可能与SRRP改善肝脏脂质代谢物水平有关。Western blot分析显示，SRRP显著上调NAFLD小鼠肝脏ACSL1和FADS2，表明SRRP可能通过减少肝脏脂质积累来缓解NAFLD。结论ssrrp通过调节肠道菌群、肝脏代谢物、胆汁酸水平以及ACSL1和FADS2蛋白的表达，对NAFLD有改善作用，为SRRP治疗NAFLD提供了更多的科学依据和支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.