# Catalpol—a compound from Rehmannia glutinosa can improve hyperlipidemia by modulating gut microbiota and endogenous metabolic pathways

## TL;DR

Catalpol, a compound from Rehmannia glutinosa, reduces high cholesterol in rats by changing gut bacteria and restoring metabolic balance.

## Contribution

This study is the first to show catalpol's lipid-lowering effects via gut microbiota modulation and metabolic pathway restoration.

## Key findings

- Catalpol significantly reduced lipid levels and inhibited liver lipid peroxidation in hyperlipidemic rats.
- Catalpol treatment reversed HFD-induced changes in gut microbiota and endogenous metabolite profiles.
- Lactobacillus and pteridine were identified as key contributors to catalpol's anti-hyperlipidemic effects.

## Abstract

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 an 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 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 an HFD led to a significant increase in the abundance of Firmicutes and a decrease in that of Bacteroidetes. Notably, catalpol treatment improved HL model rats’ overall gut microbiota structure. 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.

Flowchart illustrating the analysis of Rehmannia glutinosa's effect on hyperlipidemia. It starts with purification of Catalpol, an effective treatment. Sections describe efficacy (liver appearance, blood lipid levels, enzyme activity), gut microbiota (using rat feces for 16S rRNA sequencing and diversity analysis), and analysis strategy (Catalpol identification and UHPLC-Q Exactive MS analysis). It includes metabolomics with PCA, PLS-DA, and OPLS-DA techniques, profiling of biological samples, and Spearman correlation for differential metabolites.