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Oridonin ameliorates carbon tetrachloride‐induced liver fibrosis in mice through inhibition of the NLRP3 inflammasome
Author(s) -
Liu Dong,
Qin Hailong,
Yang Bixian,
Du Bin,
Yun Xuelin
Publication year - 2020
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21649
Subject(s) - sirius red , inflammasome , hepatic stellate cell , fibrosis , carbon tetrachloride , liver injury , pharmacology , ccl4 , inflammation , apoptosis , medicine , hepatic fibrosis , extracellular matrix , chemistry , cancer research , immunology , pathology , biochemistry , organic chemistry
Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) and accumulation of the extracellular matrix. There are limitations in the current therapies for liver fibrosis. Recently, oridonin was shown to induce apoptosis in HSCs. Thus, we aimed to determine the roles of oridonin in chronic liver injury and fibrosis. Liver fibrosis was induced by CCl 4 in mice injected intraperitoneally with oridonin for 6 weeks. The administration of oridonin significantly attenuated liver injury and reduced ALT levels. In addition, Sirius Red staining and the expression of α‐smooth muscle actin (α‐SMA) were significantly reduced by oridonin in murine livers with fibrosis. The expression of NLRP3, caspase‐1, and IL‐1β was downregulated with the oridonin treatment. Furthermore, the expression of F4/80 in liver tissues was also decreased by oridonin treatment. These results demonstrate that oridonin ameliorates chronic liver injury and fibrosis. Mechanically, oridonin may inhibit the activity of the NLRP3 inflammasome and inflammation in the liver. These results highlight the potential of oridonin as a therapeutic agent for liver fibrosis.