2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolism
BackgroundThe 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.MethodsIn this study, a liver fibrosis model was established in K...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1581138/full |
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| author | Yongfei He Thi Thai Hoa Pham Junming Xu Shengjie Hong Jicai Wang Hang Zhai Qiang Tao Ruixi Li Guangquan Zhang Xianjie Shi |
| author_facet | Yongfei He Thi Thai Hoa Pham Junming Xu Shengjie Hong Jicai Wang Hang Zhai Qiang Tao Ruixi Li Guangquan Zhang Xianjie Shi |
| author_sort | Yongfei He |
| collection | DOAJ |
| description | BackgroundThe 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.MethodsIn 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.ResultsThe 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.ConclusionOur study suggests that DMDD alleviates liver fibrosis by inhibiting the TGF-β/Smad signaling pathway, restoring gut microbiota homeostasis, and balancing bile acid metabolism. |
| format | Article |
| id | doaj-art-a443315a256e4640b3a17ccfed707fe5 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-a443315a256e4640b3a17ccfed707fe52025-08-20T03:49:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.158113815811382-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolismYongfei He0Thi Thai Hoa Pham1Junming Xu2Shengjie Hong3Jicai Wang4Hang Zhai5Qiang Tao6Ruixi Li7Guangquan Zhang8Xianjie Shi9Department of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, ChinaZhuang & Yao Medicine Research and Development Center, Guangxi International Zhuang Medicine Hospital is Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, ChinaBackgroundThe 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.MethodsIn 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.ResultsThe 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.ConclusionOur study suggests that DMDD alleviates liver fibrosis by inhibiting the TGF-β/Smad signaling pathway, restoring gut microbiota homeostasis, and balancing bile acid metabolism.https://www.frontiersin.org/articles/10.3389/fphar.2025.1581138/full2-dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dioneliver fibrosisbile acid metabolismintestinal floratranscriptomics |
| spellingShingle | Yongfei He Thi Thai Hoa Pham Junming Xu Shengjie Hong Jicai Wang Hang Zhai Qiang Tao Ruixi Li Guangquan Zhang Xianjie Shi 2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolism Frontiers in Pharmacology 2-dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione liver fibrosis bile acid metabolism intestinal flora transcriptomics |
| title | 2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolism |
| title_full | 2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolism |
| title_fullStr | 2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolism |
| title_full_unstemmed | 2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolism |
| title_short | 2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolism |
| title_sort | 2 dodecyl 6 methoxycyclohexa 2 5 dien 1 4 dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolism |
| topic | 2-dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione liver fibrosis bile acid metabolism intestinal flora transcriptomics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1581138/full |
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