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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Food Microbiology

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1689778

This article is part of the Research TopicNew Insights in Multifunctional Foods: Applications of Postbiotics, Pharmabiotics, Psychobiotics, Parabiotics, and CobioticsView all 3 articles

Catalpol: a compound from rehmannia glutinosa can improve hyperlipidemia by modulating gut microbiota and endogenous metabolic pathways

Provisionally accepted
Long  DaiLong Dai1*Xinfeng  PeiXinfeng Pei1Weichao  DongWeichao Dong2Yingying  YuYingying Yu2Shaoping  WangShaoping Wang2Yinglei  WangYinglei Wang2
  • 1Shandong University of Traditional Chinese Medicine, Jinan, China
  • 2Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China

The final, formatted version of the article will be published soon.

Catalpol, an iridoid glycoside derived from Rehmannia glutinosa, is widely recognized for its ability to reduce blood glucose levels. However, its potential therapeutic effects on hyperlipidemia (HL) have yet to be investigated. To identify novel lipid-lowering effects of catalpol potentially exerted through the modulation of the gut microbiota and endogenous metabolic pathways, Sprague–Dawley (SD) rats were provided a high-fat diet (HFD) to induce a HL state. The lipid-lowering efficacy of catalpol was assessed using biochemical test kits. Subsequently, 16S rRNA gene sequencing was employed to analyze alterations in gut microbial composition in HL rats before and after catalpol treatment. Ultra-high-performance liquid chromatography coupled with Quadrupole Exactive Orbitrap mass spectrometry (UHPLC-Q Exactive Orbitrap MS) was used to detect and identify catalpol 2 metabolites in plasma, urine, and feces. In addition, non-targeted metabolomics was conducted to characterize endogenous small-molecule metabolites. Pharmacodynamic analysis demonstrated that catalpol markedly reduced lipid levels and inhibited hepatic lipid peroxidation. The 16S rRNA sequencing results showed that the consumption of a HFD led to a significant increase in the abundance of Firmicutes and a decrease in that of Bacteroidetes. Notably, catalpol treatment improved the overall gut microbiota structure in HL model rats. Non-targeted metabolomics revealed that the HFD significantly altered the abundance of 18 endogenous metabolites, changes that were reversed following catalpol administration. Spearman correlation analysis identified the genus Lactobacillus as a positive contributor to the anti-HL effect of catalpol. Furthermore, pteridine was identified as a potential biomarker associated with catalpol's lipid-lowering activity. Collectively, these findings demonstrate that catalpol alleviates HL by influencing gut microbiota composition and restoring plasma metabolic homeostasis.

Keywords: Catalpol, Hyperlipidemia, Metabolomics, 16S rRNA gene sequencing, Correlation analysis

Received: 20 Aug 2025; Accepted: 20 Oct 2025.

Copyright: © 2025 Dai, Pei, Dong, Yu, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Long Dai, 2233493924@qq.com

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