Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2022.077
Loganin Prevents Hepatic Steatosis by Blocking NLRP3 Inflammasome Activation
Joo Hyeon Jang1,†, Gabsik Yang2,†, Jin Kyung Seok1, Han Chang Kang1, Yong-Yeon Cho1, Hye Suk Lee1 and Joo Young Lee1,*
1College of Pharmacy, The Catholic University of Korea, Bucheon 14662,
2Department of Pharmacology, College of Korean Medicine, Woosuk University, Jeonju 54986, Republic of Korea
*E-mail: joolee@catholic.ac.kr
Tel: +82-2-2164-4095, Fax: +82-2-2164-4059
The first two authors contributed equally to this work.
Received: June 4, 2022; Revised: August 24, 2022; Accepted: August 25, 2022; Published online: September 16, 2022.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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: Phytochemical, Inflammasome, Liver, Steatosis, Fibrosis, Inflammation


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