Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Loganin Prevents Hepatic Steatosis by Blocking NLRP3 Inflammasome Activation

  • Joo Hyeon, Jang (College of Pharmacy, The Catholic University of Korea) ;
  • Gabsik, Yang (Department of Pharmacology, College of Korean Medicine, Woosuk University) ;
  • Jin Kyung, Seok (College of Pharmacy, The Catholic University of Korea) ;
  • Han Chang, Kang (College of Pharmacy, The Catholic University of Korea) ;
  • Yong-Yeon, Cho (College of Pharmacy, The Catholic University of Korea) ;
  • Hye Suk, Lee (College of Pharmacy, The Catholic University of Korea) ;
  • Joo Young, Lee (College of Pharmacy, The Catholic University of Korea)
  • Received : 2022.06.04
  • Accepted : 2022.08.25
  • Published : 2023.01.01
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Abstract

Activation of the NLRP3 inflammasome is a necessary process to induce fibrosis in nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is a kind of NAFLD that encompasses the spectrum of liver disease. It is characterized by inflammation and ballooning of hepatocytes during steatosis. We tested whether inhibiting the NLRP3 inflammasome could prevent the development and pathology of NASH. We identified loganin as an inhibitor of the NLRP3 inflammasome and investigated whether in vivo administration of loganin prevented NASH symptoms using a methionine-choline deficient (MCD) diet model in mice. We found that loganin inhibited the NLRP3 inflammasome activation triggered by ATP or nigericin, as shown by suppression of the production of interleukin (IL)-1β and caspase-1 (p10) in mouse primary macrophages. The speck formation of apoptosisassociated speck-like protein containing a caspase recruitment domain (ASC) was blocked by loganin, showing that the assembly of the NLRP3 inflammasome complex was impaired by loganin. Administration of loganin reduced the clinical signs of NASH in mice fed the MCD diet, including hepatic inflammation, fat accumulation, and fibrosis. In addition, loganin reduced the expression of NLRP3 inflammasome components in the liver. Our findings indicate that loganin alleviates the inflammatory symptoms associated with NASH, presumably by inhibiting NLRP3 inflammasome activation. In summary, these findings imply that loganin may be a novel nutritional and therapeutic treatment for NASH-related inflammation.

Keywords

Acknowledgement

This study was supported by grants from the National Research Foundation of Korea (NRF) (NRF-2019R1A2C2085739 and NRF-2020R1A4A2002894) funded by the Korean government (Ministry of Science, ICT and Future Planning).

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