Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation

Qi Feng, Chen Liu, Wei Gao, Xiao-ling Geng, Ning Dai Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, People’s Republic of ChinaCorrespondence: Ning DaiDepartment of Gastroenterology, The First Affiliated Hospital...

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Autores principales:	Feng Q, Liu C, Gao W, Geng X, Dai N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	non-alcoholic fatty liver disease salidroside trpm2 ion channel autophagy cytokines Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/366d5699ba5e4a4abd29682ba21d56de
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spelling	oai:doaj.org-article:366d5699ba5e4a4abd29682ba21d56de2021-12-02T09:22:29ZSalidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation1178-7007https://doaj.org/article/366d5699ba5e4a4abd29682ba21d56de2019-12-01T00:00:00Zhttps://www.dovepress.com/salidroside-mitigated-inflammatory-injury-of-hepatocytes-with-non-alco-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Qi Feng, Chen Liu, Wei Gao, Xiao-ling Geng, Ning Dai Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, People’s Republic of ChinaCorrespondence: Ning DaiDepartment of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Zhongshan Road, Dalian, 116011, Liaoning Province, People’s Republic of ChinaTel +86 411 83635963Fax +86 411 83635965Email ning_dldn@outlook.comPurpose: Oxidative stress plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). TRPM2 ion channel functions as a molecular sensor for oxidative stress. The aim of this study was to examine the protective effects of Salidroside, a powerful antioxidative plant, on TRPM2 in an established in vitro model of NAFLD.Methods: NAFLD model was established by palmitic acid (PA) in hepatic L02 cell lines and was added to the media at a final concentration of 400 μM. Cells were used as normal group, PA group and PA receiving varied concentrations of Salidroside (75μg/mL, 150μg/mL, 300μg/mL). After treating 24 hrs, MTT assay was used to detect cell viability, and ALT level was measured using an appropriate kit assay. Intracellular lipid accumulation was observed by Oil red O staining. Cytosolic Ca2+ concentrations were evaluated by flow cytometer with Fluo-3/AM. Quantitative RT-PCR was used to measure the mRNA expression of TRPM2, IL-1β and IL-6, and the protein expressions of TRPM2, p-CaMKII and autophagy (LC3B, p62) were determined using Western blot.Results: Treatment with Salidroside effectively restored liver injury and alleviated lipid droplet deposition in a dose-dependent manner, which was associated with inhibition of TRPM2/Ca2+/CaMKII pathway. Additionally, autophagic clearance was enhanced by intervention with Salidroside in a dose-dependent manner. Further investigation indicated that Salidroside down-regulated the mRNA expression of IL-1β and IL-6-pro-inflammatory cytokines.Conclusion: These results suggest that Salidroside could alleviate inflammatory injury and steatosis via autophagy activation mediated by downregulation of the TRPM2/Ca2+/CaMKII pathway. Targeting the TRPM2 ion channel is a novel treatment strategy for oxidative stress-induced liver in NAFLD.Keywords: non-alcoholic fatty liver disease, salidroside, TRPM2 ion channel, autophagy, cytokinesFeng QLiu CGao WGeng XDai NDove Medical Pressarticlenon-alcoholic fatty liver diseasesalidrosidetrpm2 ion channelautophagycytokinesSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 2755-2763 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	non-alcoholic fatty liver disease salidroside trpm2 ion channel autophagy cytokines Specialties of internal medicine RC581-951
spellingShingle	non-alcoholic fatty liver disease salidroside trpm2 ion channel autophagy cytokines Specialties of internal medicine RC581-951 Feng Q Liu C Gao W Geng X Dai N Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation
description	Qi Feng, Chen Liu, Wei Gao, Xiao-ling Geng, Ning Dai Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, People’s Republic of ChinaCorrespondence: Ning DaiDepartment of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Zhongshan Road, Dalian, 116011, Liaoning Province, People’s Republic of ChinaTel +86 411 83635963Fax +86 411 83635965Email ning_dldn@outlook.comPurpose: Oxidative stress plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). TRPM2 ion channel functions as a molecular sensor for oxidative stress. The aim of this study was to examine the protective effects of Salidroside, a powerful antioxidative plant, on TRPM2 in an established in vitro model of NAFLD.Methods: NAFLD model was established by palmitic acid (PA) in hepatic L02 cell lines and was added to the media at a final concentration of 400 μM. Cells were used as normal group, PA group and PA receiving varied concentrations of Salidroside (75μg/mL, 150μg/mL, 300μg/mL). After treating 24 hrs, MTT assay was used to detect cell viability, and ALT level was measured using an appropriate kit assay. Intracellular lipid accumulation was observed by Oil red O staining. Cytosolic Ca2+ concentrations were evaluated by flow cytometer with Fluo-3/AM. Quantitative RT-PCR was used to measure the mRNA expression of TRPM2, IL-1β and IL-6, and the protein expressions of TRPM2, p-CaMKII and autophagy (LC3B, p62) were determined using Western blot.Results: Treatment with Salidroside effectively restored liver injury and alleviated lipid droplet deposition in a dose-dependent manner, which was associated with inhibition of TRPM2/Ca2+/CaMKII pathway. Additionally, autophagic clearance was enhanced by intervention with Salidroside in a dose-dependent manner. Further investigation indicated that Salidroside down-regulated the mRNA expression of IL-1β and IL-6-pro-inflammatory cytokines.Conclusion: These results suggest that Salidroside could alleviate inflammatory injury and steatosis via autophagy activation mediated by downregulation of the TRPM2/Ca2+/CaMKII pathway. Targeting the TRPM2 ion channel is a novel treatment strategy for oxidative stress-induced liver in NAFLD.Keywords: non-alcoholic fatty liver disease, salidroside, TRPM2 ion channel, autophagy, cytokines
format	article
author	Feng Q Liu C Gao W Geng X Dai N
author_facet	Feng Q Liu C Gao W Geng X Dai N
author_sort	Feng Q
title	Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation
title_short	Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation
title_full	Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation
title_fullStr	Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation
title_full_unstemmed	Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation
title_sort	salidroside-mitigated inflammatory injury of hepatocytes with non-alcoholic fatty liver disease via inhibition trpm2 ion channel activation
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/366d5699ba5e4a4abd29682ba21d56de
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Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation

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