Loganin Prevents Hepatic Steatosis by Blocking NLRP3 Inflammasome Activation
10.4062/biomolther.2022.077
- Author:
Joo Hyeon JANG
1
;
Gabsik YANG
;
Jin Kyung SEOK
;
Han Chang KANG
;
Yong-Yeon CHO
;
Hye Suk LEE
;
Joo Young LEE
Author Information
1. College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2023;31(1):40-47
- CountryRepublic of Korea
- Language:English
-
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.
