Loganin Prevents Hepatic Steatosis by Blocking NLRP3 Inflammasome Activation

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.

Loganin alleviates myocardial ischemia–reperfusion injury through GLP‐1R/NLRP3‐mediated pyroptosis pathway

“…Jang et al reported that loganin could block NLRP3 activation in hepatic steatosis. 22 Choi et al suggested that loganin relieved gout inflammation through inhibiting activation of NLRP3 inflammasome. 14 Moreover, Zhang et al showed loganin could attenuate lung injury induced by sepsis through repressing NLRP3 inflammasome-mediated inflammation.…”

“…Jang et al reported that loganin could block NLRP3 activation in hepatic steatosis 22 . Choi et al suggested that loganin relieved gout inflammation through inhibiting activation of NLRP3 inflammasome 14 .…”

A potential therapeutic approach for ulcerative colitis: targeted regulation of macrophage polarization through phytochemicals

“…Loganin, a type of bioactive iridoid glycoside extracted from traditional Chinese medicine, commonly called Cornus officinalis, was established to have potent anti-depression, neuropathic protection, and anti-inflammation effects (82)(83)(84). Yuan et al reported that loganin could prominently alleviate the pathologic alterations of DSS-induced colitis, increase the tight junction proteins to protect the intestinal epithelial barrier, and inhibit the expression of colonic pro-inflammatory cytokines such as IL-1b, IL-6, and TNF-a (85).…”