Hu-lu-su-pian ameliorates hepatic steatosis by regulating CIDEA expression in AKT-driven MASLD mice
IntroductionHu-lu-su-pian (HLSP) is an oral tablet derived from the active compounds of Cucumis melo L., a traditional Chinese medicine. This contemporary formulation is frequently employed in clinical settings for the management of liver ailments. However, the molecular mechanism by which HLSP affe...
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Frontiers Media S.A.
2025-01-01
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| author | Rumeng Ren Rumeng Ren Qi Wang Qi Wang Dongjie Deng Dongjie Deng Aoao Guo Aoao Guo Xin Chen Xin Chen Yan Meng Yan Meng Ying Fang Ying Fang Guohua Zheng Guohua Zheng Zhong Xu Zhong Xu Man Li Junjie Hu Junjie Hu |
| author_facet | Rumeng Ren Rumeng Ren Qi Wang Qi Wang Dongjie Deng Dongjie Deng Aoao Guo Aoao Guo Xin Chen Xin Chen Yan Meng Yan Meng Ying Fang Ying Fang Guohua Zheng Guohua Zheng Zhong Xu Zhong Xu Man Li Junjie Hu Junjie Hu |
| author_sort | Rumeng Ren |
| collection | DOAJ |
| description | IntroductionHu-lu-su-pian (HLSP) is an oral tablet derived from the active compounds of Cucumis melo L., a traditional Chinese medicine. This contemporary formulation is frequently employed in clinical settings for the management of liver ailments. However, the molecular mechanism by which HLSP affects metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. This study aimed to explore the therapeutic potential of HLSP on MASLD and the underlying mechanism.MethodsThe researchers used ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) to identify the primary chemical components of HLSP. A mouse model of MASLD induced by AKT was established through hydrodynamic transfection with activated forms of AKT. Serum biochemical indices and liver pathological assessments were employed to evaluate the pharmacodynamic effects of HLSP on MASLD. Transcriptomic analysis of the liver was conducted to detect differentially expressed genes (DEGs). Further examination of significant DEGs and proteins was performed using quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry (IHC) techniques, respectively. The efficacy and molecular mechanisms of HLSP in MASLD were further explored in HepG2 and Huh-7 cells in the presence of gene overexpression.ResultsFrom the UPLC-Q-TOF-MS/MS results, we detected fifteen components from HLSP. From the results of serum biochemical indices and hepatic pathology analyses, it is clear that HLSP is effective in treating MASLD. The findings from hepatic transcription studies revealed CIDEA as an essential DEG that facilitates lipid droplet (LD) fusion and enhances de novo fatty acid synthesis from scratch in cases of hepatic steatosis, which HLSP has the potential to counteract. In addition, HLSP significantly reduced lipid accumulation and expression of critical genes for de novo fatty acid synthesis in HepG2 and Huh-7 cells overexpressing CIDEA.DiscussionThe present study preliminarily suggests that HLSP can ameliorate hepatic steatosis by inhibiting CIDEA-mediated de novo fatty acid synthesis and LD formation, which may offer a potential strategy for treating MASLD. |
| format | Article |
| id | doaj-art-8a5316efcb964a398c0e719a432f253d |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-8a5316efcb964a398c0e719a432f253d2025-01-31T06:40:05ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15032471503247Hu-lu-su-pian ameliorates hepatic steatosis by regulating CIDEA expression in AKT-driven MASLD miceRumeng Ren0Rumeng Ren1Qi Wang2Qi Wang3Dongjie Deng4Dongjie Deng5Aoao Guo6Aoao Guo7Xin Chen8Xin Chen9Yan Meng10Yan Meng11Ying Fang12Ying Fang13Guohua Zheng14Guohua Zheng15Zhong Xu16Zhong Xu17Man Li18Junjie Hu19Junjie Hu20School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaSchool of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaSchool of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaSchool of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaSchool of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaSchool of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaSchool of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaSchool of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaDepartment of Gastroenterology, Zhongnan Hospital of Wuhan University, Health Management Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, ChinaGuizhou Provincial People’s Hospital, Guiyang, Guizhou, ChinaDepartment of Integrated Traditional and Western Medicine, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaSchool of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaIntroductionHu-lu-su-pian (HLSP) is an oral tablet derived from the active compounds of Cucumis melo L., a traditional Chinese medicine. This contemporary formulation is frequently employed in clinical settings for the management of liver ailments. However, the molecular mechanism by which HLSP affects metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. This study aimed to explore the therapeutic potential of HLSP on MASLD and the underlying mechanism.MethodsThe researchers used ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) to identify the primary chemical components of HLSP. A mouse model of MASLD induced by AKT was established through hydrodynamic transfection with activated forms of AKT. Serum biochemical indices and liver pathological assessments were employed to evaluate the pharmacodynamic effects of HLSP on MASLD. Transcriptomic analysis of the liver was conducted to detect differentially expressed genes (DEGs). Further examination of significant DEGs and proteins was performed using quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry (IHC) techniques, respectively. The efficacy and molecular mechanisms of HLSP in MASLD were further explored in HepG2 and Huh-7 cells in the presence of gene overexpression.ResultsFrom the UPLC-Q-TOF-MS/MS results, we detected fifteen components from HLSP. From the results of serum biochemical indices and hepatic pathology analyses, it is clear that HLSP is effective in treating MASLD. The findings from hepatic transcription studies revealed CIDEA as an essential DEG that facilitates lipid droplet (LD) fusion and enhances de novo fatty acid synthesis from scratch in cases of hepatic steatosis, which HLSP has the potential to counteract. In addition, HLSP significantly reduced lipid accumulation and expression of critical genes for de novo fatty acid synthesis in HepG2 and Huh-7 cells overexpressing CIDEA.DiscussionThe present study preliminarily suggests that HLSP can ameliorate hepatic steatosis by inhibiting CIDEA-mediated de novo fatty acid synthesis and LD formation, which may offer a potential strategy for treating MASLD.https://www.frontiersin.org/articles/10.3389/fphar.2024.1503247/fullHu-lu-su-pianmetabolic dysfunction-associated steatotic liver diseaseCIDEAde novo fatty acid synthesislipid droplets |
| spellingShingle | Rumeng Ren Rumeng Ren Qi Wang Qi Wang Dongjie Deng Dongjie Deng Aoao Guo Aoao Guo Xin Chen Xin Chen Yan Meng Yan Meng Ying Fang Ying Fang Guohua Zheng Guohua Zheng Zhong Xu Zhong Xu Man Li Junjie Hu Junjie Hu Hu-lu-su-pian ameliorates hepatic steatosis by regulating CIDEA expression in AKT-driven MASLD mice Frontiers in Pharmacology Hu-lu-su-pian metabolic dysfunction-associated steatotic liver disease CIDEA de novo fatty acid synthesis lipid droplets |
| title | Hu-lu-su-pian ameliorates hepatic steatosis by regulating CIDEA expression in AKT-driven MASLD mice |
| title_full | Hu-lu-su-pian ameliorates hepatic steatosis by regulating CIDEA expression in AKT-driven MASLD mice |
| title_fullStr | Hu-lu-su-pian ameliorates hepatic steatosis by regulating CIDEA expression in AKT-driven MASLD mice |
| title_full_unstemmed | Hu-lu-su-pian ameliorates hepatic steatosis by regulating CIDEA expression in AKT-driven MASLD mice |
| title_short | Hu-lu-su-pian ameliorates hepatic steatosis by regulating CIDEA expression in AKT-driven MASLD mice |
| title_sort | hu lu su pian ameliorates hepatic steatosis by regulating cidea expression in akt driven masld mice |
| topic | Hu-lu-su-pian metabolic dysfunction-associated steatotic liver disease CIDEA de novo fatty acid synthesis lipid droplets |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1503247/full |
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