The improvement effect of gastrodin on LPS/GalN-induced fulminant hepatitis via inhibiting inflammation and apoptosis and restoring autophagy |
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Institution: | 1. College of Pharmacy, South-Central University for Nationalities, Wuhan, PR China;2. Department of Endocrinology, Wuhan General Hospital of Guangzhou Military Command, Wuhan, PR China;1. Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi''an, Shaanxi Province 710032, P.R.China;2. Department of Natural Medicine, Institute of Materia Medica, School of Pharmacy, The Fourth Military Medical University, Xi''an, Shaanxi Province 710032, P.R.China;3. Student Brigade, The Fourth Military Medical University, Xi''an, Shaanxi Province 710032, P.R.China;4. Department of Diagnostic Radiology, Tangdu Hospital, The Fourth Military Medical University, Xi''an, Shaanxi Province 710032, P.R.China |
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Abstract: | Fulminant hepatitis (FH), characterized by overwhelmed inflammation and massive hepatocyte apoptosis, is a life-threatening and high mortality rate. Gastrodin (GTD), a phenolic glucoside extracted from Gastrodiaelata Blume, exerts anti-apoptosis, and anti-inflammatory activities. In the present study, we aimed to evaluate whether GTD treatment could alleviate lipopolysaccharide and d-galactosamine (LPS/GalN)-induced FH in mice and its potential mechanisms. These data suggested that GTD treatment remarkably protected against LPS/GalN-induced FH by enhancing the survival rate of mice, reducing ALT and AST levels, attenuating histopathological changes, and suppressing interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α secretion. In addition, GTD treatment relieved hepatic apoptosis by the regulation of peroxisome proliferator-activated receptors (PPARs), P53 and caspase-3/9. Furthermore, GTD treatment could significantly inhibit inflammation-related signaling pathways activated by LPS/GalN, including the suppression of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) and nuclear factor-kappa B (NF-κB) activation. Importantly, GTD treatment effectively restored but not induced LPS/GalN-reduced the expression of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, as well as the level of pro-autophagy proteins. Taken together, our investigation indicated that GTD played an essential role in liver protection by relieving hepatocyte apoptosis and inflammation reaction, which may be closely involved in the inhibition of NLRP3 inflammasome and NF-κB activation, regulation of apoptosis-related proteins expression, and the recovery of AMPK/ACC/autophagy. |
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Keywords: | Fulminant hepatitis Gastrodin Inflammation Hepatocyte apoptosis Signaling pathway ACC"} {"#name":"keyword" "$":{"id":"k0035"} "$$":[{"#name":"text" "_":"acetyl-CoA carboxylase ALT"} {"#name":"keyword" "$":{"id":"k0045"} "$$":[{"#name":"text" "_":"Alanine transaminase AMPK"} {"#name":"keyword" "$":{"id":"k0055"} "$$":[{"#name":"text" "_":"AMP-activated protein kinase AST"} {"#name":"keyword" "$":{"id":"k0065"} "$$":[{"#name":"text" "_":"aspartate aminotransferase FH"} {"#name":"keyword" "$":{"id":"k0075"} "$$":[{"#name":"text" "_":"Fulminant hepatitis GTD"} {"#name":"keyword" "$":{"id":"k0085"} "$$":[{"#name":"text" "_":"gastrodin GalN"} {"#name":"keyword" "$":{"id":"k0095"} "$$":[{"#name":"text" "_":"d-galactosamine LPS"} {"#name":"keyword" "$":{"id":"k0105"} "$$":[{"#name":"text" "_":"lipopolysaccharide NLRP3"} {"#name":"keyword" "$":{"id":"k0115"} "$$":[{"#name":"text" "_":"nucleotide-binding domain (NOD)-like receptor protein 3 NF-κB"} {"#name":"keyword" "$":{"id":"k0125"} "$$":[{"#name":"text" "_":"nuclear factor-kappa B PPARs"} {"#name":"keyword" "$":{"id":"k0135"} "$$":[{"#name":"text" "_":"peroxisome proliferator-activated receptors TNF-α"} {"#name":"keyword" "$":{"id":"k0145"} "$$":[{"#name":"text" "_":"tumor necrosis factor |
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