Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Jolkinolide B Ameliorates Liver Inflammation and Lipogenesis by Regulating JAK/STAT3 Pathway

  • Hye-Rin Noh (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Guoyan Sui (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Jin Woo Lee (College of Pharmacy, Duksung Women's University) ;
  • Feng Wang (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Jeong-Su Park (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Yuanqiang Ma (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Hwan Ma (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Ji-Won Jeong (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Dong-Su Shin (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Xuefeng Wu (Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Department of Immunology and Microbiology, Hongqiao International Institute of Medicine, Shanghai Ton-gren Hospital, Shanghai Jiao Tong University School of Medicine) ;
  • Bang-Yeon Hwang (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Yoon Seok Roh (College of Pharmacy and Medical Research Center, Chungbuk National University)
  • Received : 2024.02.27
  • Accepted : 2024.07.02
  • Published : 2024.11.01
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Abstract

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

Keywords

Acknowledgement

This research was supported by National Research Foundation of Korea (2017R1A5A2015541), Korean Food and Drug Administration (20182MFDS425), Regional Innovation Strategy (RIS) of National Research Foundation of Korea (2021RIS-001), Chungbuk National University BK21 program (2023).

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