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Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome

Non-alcoholic steatohepatitis (NASH), a type of non-alcoholic fatty liver disease, is characterized as steatosis and inflammation in the liver. NLRP3 inflammasome activation is associated with NASH pathology. We hypothesized that suppressing the NLRP3 inflammasome could be effective in preventing NA...

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Autores principales: Yang, Gabsik, Jang, Joo Hyeon, Kim, Sung Wook, Han, Sin-Hee, Ma, Kyung-Ho, Jang, Jae-Ki, Kang, Han Chang, Cho, Yong-Yeon, Lee, Hye Suk, Lee, Joo Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216241/
https://www.ncbi.nlm.nih.gov/pubmed/32316419
http://dx.doi.org/10.3390/ijms21082790
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author Yang, Gabsik
Jang, Joo Hyeon
Kim, Sung Wook
Han, Sin-Hee
Ma, Kyung-Ho
Jang, Jae-Ki
Kang, Han Chang
Cho, Yong-Yeon
Lee, Hye Suk
Lee, Joo Young
author_facet Yang, Gabsik
Jang, Joo Hyeon
Kim, Sung Wook
Han, Sin-Hee
Ma, Kyung-Ho
Jang, Jae-Ki
Kang, Han Chang
Cho, Yong-Yeon
Lee, Hye Suk
Lee, Joo Young
author_sort Yang, Gabsik
collection PubMed
description Non-alcoholic steatohepatitis (NASH), a type of non-alcoholic fatty liver disease, is characterized as steatosis and inflammation in the liver. NLRP3 inflammasome activation is associated with NASH pathology. We hypothesized that suppressing the NLRP3 inflammasome could be effective in preventing NASH. We searched substances that could inhibit the activation of the NLRP3 inflammasome and identified sweroside as an NLRP3 inhibitor. We investigated whether sweroside can be applied to prevent the pathological symptoms associated with NASH in a methionine–choline-deficient (MCD) diet-induced NASH mouse model. The activation of the NLRP3 inflammasome was determined by detecting the production of caspase-1 and IL-1β from pro-caspase-1 and pro-IL-1β in primary mouse macrophages and mouse liver. In a NASH model, mice were fed an MCD diet for two weeks with daily intraperitoneal injections of sweroside. Sweroside effectively inhibited NLRP3 inflammasome activation in primary macrophages as shown by a decrease in IL-1β and caspase-1 production. In a MCD diet-induced NASH mouse model, intraperitoneal injection of sweroside significantly reduced serum aspartate transaminase and alanine transaminase levels, hepatic immune cell infiltration, hepatic triglyceride accumulation, and liver fibrosis. The improvement of NASH symptoms by sweroside was accompanied with its inhibitory effects on the hepatic NLRP3 inflammasome as hepatic IL-1β and caspase-1 were decreased. Furthermore, sweroside blocked de novo synthesis of mitochondrial DNA in the liver, contributing to suppression of the NLRP3 inflammasome. These results suggest that targeting the NLRP3 inflammasome with sweroside could be beneficially employed to improve NASH symptoms.
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spelling pubmed-72162412020-05-22 Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome Yang, Gabsik Jang, Joo Hyeon Kim, Sung Wook Han, Sin-Hee Ma, Kyung-Ho Jang, Jae-Ki Kang, Han Chang Cho, Yong-Yeon Lee, Hye Suk Lee, Joo Young Int J Mol Sci Article Non-alcoholic steatohepatitis (NASH), a type of non-alcoholic fatty liver disease, is characterized as steatosis and inflammation in the liver. NLRP3 inflammasome activation is associated with NASH pathology. We hypothesized that suppressing the NLRP3 inflammasome could be effective in preventing NASH. We searched substances that could inhibit the activation of the NLRP3 inflammasome and identified sweroside as an NLRP3 inhibitor. We investigated whether sweroside can be applied to prevent the pathological symptoms associated with NASH in a methionine–choline-deficient (MCD) diet-induced NASH mouse model. The activation of the NLRP3 inflammasome was determined by detecting the production of caspase-1 and IL-1β from pro-caspase-1 and pro-IL-1β in primary mouse macrophages and mouse liver. In a NASH model, mice were fed an MCD diet for two weeks with daily intraperitoneal injections of sweroside. Sweroside effectively inhibited NLRP3 inflammasome activation in primary macrophages as shown by a decrease in IL-1β and caspase-1 production. In a MCD diet-induced NASH mouse model, intraperitoneal injection of sweroside significantly reduced serum aspartate transaminase and alanine transaminase levels, hepatic immune cell infiltration, hepatic triglyceride accumulation, and liver fibrosis. The improvement of NASH symptoms by sweroside was accompanied with its inhibitory effects on the hepatic NLRP3 inflammasome as hepatic IL-1β and caspase-1 were decreased. Furthermore, sweroside blocked de novo synthesis of mitochondrial DNA in the liver, contributing to suppression of the NLRP3 inflammasome. These results suggest that targeting the NLRP3 inflammasome with sweroside could be beneficially employed to improve NASH symptoms. MDPI 2020-04-17 /pmc/articles/PMC7216241/ /pubmed/32316419 http://dx.doi.org/10.3390/ijms21082790 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Gabsik
Jang, Joo Hyeon
Kim, Sung Wook
Han, Sin-Hee
Ma, Kyung-Ho
Jang, Jae-Ki
Kang, Han Chang
Cho, Yong-Yeon
Lee, Hye Suk
Lee, Joo Young
Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome
title Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome
title_full Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome
title_fullStr Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome
title_full_unstemmed Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome
title_short Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome
title_sort sweroside prevents non-alcoholic steatohepatitis by suppressing activation of the nlrp3 inflammasome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216241/
https://www.ncbi.nlm.nih.gov/pubmed/32316419
http://dx.doi.org/10.3390/ijms21082790
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