Effects of scoparone on non-alcoholic fatty liver disease revealed by RNA sequencing

Scoparone (SCO) is known to have curative effect of alleviating liver injury. The purpose of this study was to observe the therapeutic effect and possible mechanism of SCO against high-fat diet (HFD) induced non-alcoholic liver disease (NAFLD) through in vivo experiments and RNA sequencing. Male Kunming mice were fed with HFD for 8 weeks to establish a mouse model of NAFLD, and SCO was used to treat NAFLD. Histopathology and biochemical indicators were used to evaluate the liver injury and the efficacy of SCO. RNA sequencing analysis was performed to elucidate the hepatoprotective mechanism of SCO. Finally, the differentially expressed genes of cholesterol synthesis and fatty acid (triglyceride) synthesis pathways were verified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The histopathological results showed that HFD could lead to significant steatosis in mice, while SCO could alleviate liver steatosis remarkably in NAFLD mice. The determination of biochemical indicators showed that SCO could inhibit the increased serum transaminase activity and liver lipid level induced by HFD. RNA sequencing analysis of liver tissues found that 2742 and 3663 genes were significantly changed by HFD and SCO, respectively. SCO reversed the most of genes involved in cholesterol synthesis and fatty acid (triglyceride) metabolism induced by HFD. the results of the validation experiment were mostly consistent with the RNA sequencing. SCO alleviated liver injury and steatosis in NAFLD mice, which may be closely related to the regulation of cholesterol and fatty acid (triglyceride) metabolism.

[1]  H. Hagström,et al.  Statins are under-used in women with NAFLD after cardiovascular events compared to matched controls. , 2022, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[2]  K. Abdelkawy,et al.  A randomized controlled trial comparing the effects of Vitamin E, Ursodeoxycholic acid and Pentoxifylline on Egyptian non-alcoholic steatohepatitis patients. , 2021, European review for medical and pharmacological sciences.

[3]  Y. Yılmaz,et al.  Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver. , 2021, Journal of clinical and translational hepatology.

[4]  H. Jun,et al.  Ethanol Extract of Liriope platyphylla Root Attenuates Non-Alcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice via Regulation of Lipogenesis and Lipid Uptake , 2021, Nutrients.

[5]  T. Kawai,et al.  LH induces de novo cholesterol biosynthesis via SREBP activation in granulosa cells during ovulation in female mice. , 2021, Endocrinology.

[6]  B. Neuschwander‐Tetri,et al.  TVB-2640 (FASN inhibitor) for the treatment of nonalcoholic steatohepatitis: FASCINATE-1, a randomized, placebo-controlled Ph2a trial. , 2021, Gastroenterology.

[7]  Yulan Liu,et al.  Gut–Liver Axis: Liver Sinusoidal Endothelial Cells Function as the Hepatic Barrier in Colitis-Induced Liver Injury , 2021, Frontiers in Cell and Developmental Biology.

[8]  Yang Zou,et al.  LDL/HDL cholesterol ratio is associated with new-onset NAFLD in Chinese non-obese people with normal lipids: a 5-year longitudinal cohort study , 2021, Lipids in health and disease.

[9]  Cheng Huang,et al.  AMPK protects against alcohol-induced liver injury through UQCRC2 to up-regulate mitophagy , 2021, Autophagy.

[10]  D. Mashek Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD , 2020, Molecular metabolism.

[11]  Jianghui Dong,et al.  Scoparone alleviates hepatic fibrosis by inhibiting the TLR‐4/NF‐κB pathway , 2020, Journal of cellular physiology.

[12]  T. Zhao,et al.  Effects of taraxasterol against ethanol and high-fat diet-induced liver injury by regulating TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways. , 2020, Life sciences.

[13]  R. Masuzaki,et al.  Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease , 2020, International journal of molecular sciences.

[14]  Bangmao Wang,et al.  Scoparone as a therapeutic drug in liver diseases: Pharmacology, pharmacokinetics and molecular mechanisms of action. , 2020, Pharmacological research.

[15]  Yafei Chu,et al.  IGFBP5 modulates lipid metabolism and insulin sensitivity through activating AMPK pathway in non-alcoholic fatty liver disease. , 2020, Life sciences.

[16]  W. S. Kang,et al.  Unripe Rubus coreanus Miquel Extract Containing Ellagic Acid Regulates AMPK, SREBP-2, HMGCR, and INSIG-1 Signaling and Cholesterol Metabolism In Vitro and In Vivo , 2020, Nutrients.

[17]  Beibei Liu,et al.  Scoparone improves hepatic inflammation and autophagy in mice with nonalcoholic steatohepatitis by regulating the ROS/P38/Nrf2 axis and PI3K/AKT/mTOR pathway in macrophages. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[18]  Isabel R Schlaepfer,et al.  CPT1A-mediated fat oxidation, mechanisms and therapeutic potential. , 2020, Endocrinology.

[19]  T. Kellogg,et al.  Evolution of NAFLD and Its Management. , 2019, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[20]  M. La Rocca,et al.  A 5-year longitudinal cohort study on crown to implant ratio effect on marginal bone level in single implants. , 2019, Clinical implant dentistry and related research.

[21]  Tom R. Gaunt,et al.  Liver Function and Risk of Type 2 Diabetes: Bidirectional Mendelian Randomization Study , 2019, Diabetes.

[22]  A. Huttenlocher,et al.  Metformin modulates innate immune-mediated inflammation and early progression of NAFLD-associated hepatocellular carcinoma in zebrafish. , 2019, Journal of hepatology.

[23]  B. Song,et al.  Post-translational regulation of lipogenesis via AMPK-dependent phosphorylation of insulin-induced gene , 2019, Nature Communications.

[24]  I. Ahmad,et al.  Lipid pathway deregulation in advanced prostate cancer , 2018, Pharmacological research.

[25]  Yiming Lin,et al.  Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway , 2017, Gut.

[26]  W. Placek,et al.  Compounds of psoriasis with obesity and overweight. , 2017, Postepy higieny i medycyny doswiadczalnej.

[27]  S. Teichmann,et al.  A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications , 2017, Genome Medicine.

[28]  Boxi Kang,et al.  Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing , 2017, Cell.

[29]  R. Shaw,et al.  AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance. , 2017, Molecular cell.

[30]  B. Demirtas,et al.  Influence of coumarin and some coumarin derivatives on serum lipid profiles in carbontetrachloride-exposed rats , 2017, Human & experimental toxicology.

[31]  L. Henry,et al.  Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes , 2016, Hepatology.

[32]  D. Mashek,et al.  Suppression of Long Chain Acyl-CoA Synthetase 3 Decreases Hepatic de Novo Fatty Acid Synthesis through Decreased Transcriptional Activity* , 2009, The Journal of Biological Chemistry.

[33]  Robert V Farese,et al.  Triglyceride accumulation protects against fatty acid-induced lipotoxicity , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[34]  G. Farrell,et al.  Pathogenesis of NASH: How Metabolic Complications of Overnutrition Favour Lipotoxicity and Pro-Inflammatory Fatty Liver Disease. , 2018, Advances in experimental medicine and biology.