Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling

Liver fibrosis, which means a sort of the excessive accumulation of extracellular matrices (ECMs) components through the liver tissue, is considered as tissue repair or wound-healing status. This pathological stage potentially leads to cirrhosis, if not controlled, it progressively results in hepato...

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Autores principales:	Mi-Rae Shin, Jin A Lee, Minju Kim, Sehui Lee, Minhyuck Oh, Jimin Moon, Joo-Won Nam, Hyukjae Choi, Yeun-Ja Mun, Seong-Soo Roh
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	liver fibrosis Gardeniae Fructus thioacetamide AMPK/SIRT1 pathway Nrf2 signaling Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/7d551e4cc8894d7ab050780333f87f18
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spelling	oai:doaj.org-article:7d551e4cc8894d7ab050780333f87f182021-11-25T16:29:38ZGardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling10.3390/antiox101118372076-3921https://doaj.org/article/7d551e4cc8894d7ab050780333f87f182021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1837https://doaj.org/toc/2076-3921Liver fibrosis, which means a sort of the excessive accumulation of extracellular matrices (ECMs) components through the liver tissue, is considered as tissue repair or wound-healing status. This pathological stage potentially leads to cirrhosis, if not controlled, it progressively results in hepatocellular carcinoma. Herein, we investigated the pharmacological properties and underlying mechanisms of Gardeniae Fructus (GF) against thioacetamide (TAA)-induced liver fibrosis of mice model. GF not only attenuated hepatic tissue oxidation but also improved hepatic inflammation. We further confirmed that GF led to ameliorating liver fibrosis by ECMs degradations. Regarding the possible underlying mechanism of GF, we observed GF regulated epigenetic regulator, Sirtuin 1 (SIRT1), in TAA-injected liver tissue. These alterations were well supported by SIRT1 related signaling pathways through regulations of its downstream proteins including, AMP-activated protein kinase (AMPK), p47<sup>phox</sup>, NADPH oxidase 2, nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase-1, respectively. To validate the possible mechanism of GF, we used HepG2 cells with hydrogen peroxide treated oxidative stress and chronic exposure conditions via deteriorations of cellular SIRT1. Moreover, GF remarkably attenuated ECMs accumulations in transforming growth factor–β1-induced LX-2 cells relying on the SIRT1 existence. Taken together, GF attenuated liver fibrosis through AMPK/SIRT1 pathway as well as Nrf2 signaling cascades. Therefore, GF could be a clinical remedy for liver fibrosis patients in the future.Mi-Rae ShinJin A LeeMinju KimSehui LeeMinhyuck OhJimin MoonJoo-Won NamHyukjae ChoiYeun-Ja MunSeong-Soo RohMDPI AGarticleliver fibrosisGardeniae FructusthioacetamideAMPK/SIRT1 pathwayNrf2 signalingTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1837, p 1837 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	liver fibrosis Gardeniae Fructus thioacetamide AMPK/SIRT1 pathway Nrf2 signaling Therapeutics. Pharmacology RM1-950
spellingShingle	liver fibrosis Gardeniae Fructus thioacetamide AMPK/SIRT1 pathway Nrf2 signaling Therapeutics. Pharmacology RM1-950 Mi-Rae Shin Jin A Lee Minju Kim Sehui Lee Minhyuck Oh Jimin Moon Joo-Won Nam Hyukjae Choi Yeun-Ja Mun Seong-Soo Roh Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling
description	Liver fibrosis, which means a sort of the excessive accumulation of extracellular matrices (ECMs) components through the liver tissue, is considered as tissue repair or wound-healing status. This pathological stage potentially leads to cirrhosis, if not controlled, it progressively results in hepatocellular carcinoma. Herein, we investigated the pharmacological properties and underlying mechanisms of Gardeniae Fructus (GF) against thioacetamide (TAA)-induced liver fibrosis of mice model. GF not only attenuated hepatic tissue oxidation but also improved hepatic inflammation. We further confirmed that GF led to ameliorating liver fibrosis by ECMs degradations. Regarding the possible underlying mechanism of GF, we observed GF regulated epigenetic regulator, Sirtuin 1 (SIRT1), in TAA-injected liver tissue. These alterations were well supported by SIRT1 related signaling pathways through regulations of its downstream proteins including, AMP-activated protein kinase (AMPK), p47<sup>phox</sup>, NADPH oxidase 2, nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase-1, respectively. To validate the possible mechanism of GF, we used HepG2 cells with hydrogen peroxide treated oxidative stress and chronic exposure conditions via deteriorations of cellular SIRT1. Moreover, GF remarkably attenuated ECMs accumulations in transforming growth factor–β1-induced LX-2 cells relying on the SIRT1 existence. Taken together, GF attenuated liver fibrosis through AMPK/SIRT1 pathway as well as Nrf2 signaling cascades. Therefore, GF could be a clinical remedy for liver fibrosis patients in the future.
format	article
author	Mi-Rae Shin Jin A Lee Minju Kim Sehui Lee Minhyuck Oh Jimin Moon Joo-Won Nam Hyukjae Choi Yeun-Ja Mun Seong-Soo Roh
author_facet	Mi-Rae Shin Jin A Lee Minju Kim Sehui Lee Minhyuck Oh Jimin Moon Joo-Won Nam Hyukjae Choi Yeun-Ja Mun Seong-Soo Roh
author_sort	Mi-Rae Shin
title	Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling
title_short	Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling
title_full	Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling
title_fullStr	Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling
title_full_unstemmed	Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling
title_sort	gardeniae fructus attenuates thioacetamide-induced liver fibrosis in mice via both ampk/sirt1/nf-κb pathway and nrf2 signaling
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7d551e4cc8894d7ab050780333f87f18
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Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling

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