ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Gastrointestinal and Hepatic Pharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1581138

This article is part of the Research TopicEmerging Talents in Frontiers in Pharmacology: Gastrointestinal and Hepatic Pharmacology 2025View all articles

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

Provisionally accepted
Yongfei HeYongfei He1Thai Hoa Pham ThiThai Hoa Pham Thi2Xu JMXu JM1Shengjie HongShengjie Hong1Jicai WangJicai Wang1Hang ZhaiHang Zhai1Qiang TaoQiang Tao1Ruixi LiRuixi Li1Guangquan ZhangGuangquan Zhang1Xianjie ShiXianjie Shi1*
  • 1The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
  • 2Guangxi International Zhuang Medical Hospital, Nanning, Guangxi Zhuang Region, China

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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.

Keywords: 2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione, liver fibrosis, Bile acid metabolism, intestinal flora, Transcriptomics

Received: 21 Feb 2025; Accepted: 24 Apr 2025.

Copyright: © 2025 He, Pham Thi, JM, Hong, Wang, Zhai, Tao, Li, Zhang and Shi. 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: Xianjie Shi, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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