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Volume 4 Issue 3
Jul.  2024
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Article Navigation >  Frigid Zone Medicine  > 2024  >  4(3): 160-176
Wen Li, Jia Wang, Yilian Yang, Chunlei Duan, Bing Shao, Mingxiu Zhang, Jiapan Wang, Peifeng Li, Ye Yuan, Yan Zhang, Hongyu Ji, Xingda Li, Zhimin Du. Ethanol extract of cassia seed alleviates metabolic dysfunction-associated steatotic liver disease by acting on multiple lipid metabolism-related pathways[J]. Frigid Zone Medicine, 2024, 4(3): 160-176. doi: 10.1515/fzm-2024-0017
Citation: Wen Li, Jia Wang, Yilian Yang, Chunlei Duan, Bing Shao, Mingxiu Zhang, Jiapan Wang, Peifeng Li, Ye Yuan, Yan Zhang, Hongyu Ji, Xingda Li, Zhimin Du. Ethanol extract of cassia seed alleviates metabolic dysfunction-associated steatotic liver disease by acting on multiple lipid metabolism-related pathways[J]. Frigid Zone Medicine, 2024, 4(3): 160-176. doi: 10.1515/fzm-2024-0017
shu

Ethanol extract of cassia seed alleviates metabolic dysfunction-associated steatotic liver disease by acting on multiple lipid metabolism-related pathways

doi: 10.1515/fzm-2024-0017
  • 1.

    Institute of Clinical Pharmacy, the Second Affiliated Hospital of Harbin Medical University (State Key Laboratory of Frigid Zone Cardiovascular Diseases), Harbin 150086, China

  • 2.

    State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China

Funds:

National Natural Science Foundation of China 82073838

National Natural Science Foundation of China 82273917

More Information
  • Corresponding author: Zhimin Du, E-mail: dzm1956@126.com

  • #These authors made equal contributions to this work.

  • Received Date: 2024-06-28
  • Accepted Date: 2024-08-27
    • Available Online: 2024-07-01
    Abstract
  •   Background and objective  In northern China's cold regions, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) exceeds 50%, significantly higher than the national and global rates. MASLD is an important risk factor for cardiovascular and cerebrovascular diseases, including coronary heart disease, stroke, and tumors, with no specific therapeutic drugs currently available. The ethanol extract of cassia seed (CSEE) has shown promise in lowering blood lipids and improving hepatic steatosis, but its mechanism in treating MASLD remains underexplored. This study aims to investigate the therapeutic effects and mechanisms of CSEE.  Methods  MASLD models were established in male Wistar rats and golden hamsters using a high fat diet (HFD). CSEE (10, 50, 250 mg/kg) was administered via gavage for six weeks. Serum levels of total cholesterol (TC), triglyceride (TG), lowdensity lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as liver TC and TG, were measured using biochemical kits. Histopathological changes in the liver were evaluated using Oil Red O staining, Hematoxylin-eosin (H&E) staining, and transmission electron microscopy (TEM). HepG2 cell viability was assessed using the cell counting kit-8 (CCK8) and Calcein-AM/PI staining. Network pharmacology was used to analyze drug-disease targets, and western blotting was used to confirm these predictions.  Results  CSEE treatment significantly reduced serum levels of TC, TG, LDL-C, ALT, and AST, and improved liver weight, liver index, and hepatic lipid deposition in rats and golden hamsters. In addition, CSEE alleviated free fatty acid (FFA)-induced lipid deposition in HepG2 cells. Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK, p-ACC, PPARα, CPT1A, PI3K P110 and p-AKT, while decreasing the protein levels of SREBP1, FASN, C/EBPα, and PPARγ, thus improving hepatic lipid metabolism and reducing lipid deposition. The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro.  Conclusion  CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK, PPARα, and PI3K/AKT signaling pathways.

     

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