# 2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolism

**Authors:** Yongfei He, Thi Thai Hoa Pham, Junming Xu, Shengjie Hong, Jicai Wang, Hang Zhai, Qiang Tao, Ruixi Li, Guangquan Zhang, Xianjie Shi

PMC · DOI: 10.3389/fphar.2025.1581138 · Frontiers in Pharmacology · 2025-05-16

## TL;DR

A compound from star fruit reduces liver fibrosis in mice by improving gut bacteria and bile acid balance.

## Contribution

DMDD is shown to alleviate liver fibrosis by modulating the TGF-β/Smad pathway and gut microbiota.

## Key findings

- DMDD mitigates liver fibrosis in mice by suppressing the TGF-β/Smad signaling pathway.
- DMDD increases beneficial gut bacteria like Lactobacillus and Bacteroides.
- DMDD regulates bile acid metabolism, contributing to liver fibrosis alleviation.

## Abstract

The bioactive compound 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD), derived from the horn root of star fruit, exhibits therapeutic promise through its modulation of the TGF-β1 pathway and regulation of bile acids.

In this study, a liver fibrosis model was established in Kunming mice (KM) induced by carbon tetrachloride (CCL4), and DMDD (50 mg/kg) was administered intragastrically. HE staining, Masson staining, and Sirius staining were used to evaluate the effect of DMDD on liver fibrosis. The Illumina sequencing platform was used to detect intestinal flora and liver transcriptome information in mouse feces, and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technology was used to detect bile acid content changes in mouse feces.

The results show that DMDD can mitigate liver fibrosis-induced damage in mice, potentially through the suppression of the TGF-β/Smad signaling pathway. Furthermore, DMDD increased the abundance of Lactobacillus, Bacteroides, Ruminococcaceae, Ruminococcus, and Oscillospira, thereby addressing intestinal flora disturbances and regulating bile acid metabolism.

Our study suggests that DMDD alleviates liver fibrosis by inhibiting the TGF-β/Smad signaling pathway, restoring gut microbiota homeostasis, and balancing bile acid metabolism.

## Linked entities

- **Proteins:** TGFB1 (transforming growth factor beta 1), Smox (Smad on X)
- **Chemicals:** carbon tetrachloride (PubChem CID 5943)

## Full-text entities

- **Diseases:** liver fibrosis (MESH:D008103)
- **Chemicals:** 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (MESH:C581182), bile acid (MESH:D001647), CCL4 (MESH:D002251), 2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Ruminococcus (genus) [taxon 1263], Lactobacillus (genus) [taxon 1578], Ruminococcaceae [taxon 541000], Bacteroides (genus) [taxon 816], Oscillospira (genus) [taxon 119852]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12122303/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12122303/full.md

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Source: https://tomesphere.com/paper/PMC12122303