Anti-apoptotic and Hepatoprotective Effects of Gomisin A on Fulminant Hepatic Failure Induced by D-Galactosamine and Lipopolysaccharide in Mice

Kim, Sung Hwa; Kim, Yeong Shik; Kang, Sam Sik; Bae, KiHwan; Hung, Tran Manh; Lee, Sun-Mee

doi:10.1254/jphs.fp0071738

Cited by 59 publications

(32 citation statements)

References 31 publications

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“…The condensation of Kupffer cells can be seen in C. myrrha pretreated (250 and 500 mg/kg; p.o.) rats may be due to apoptosis (Kim et al, 2008). There was a marked attenuation of these inflammatory alterations in a dosedependent manner in C. myrrha pretreated rat.…”

Section: Discussionmentioning

confidence: 80%

Hepatoprotective effect ofCommiphora myrrhaagainstd-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes

Ahmad

Raish

Ganaie

et al. 2015

Pharmaceutical Biology

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(2015) Hepatoprotective effect of Commiphoramyrrha against d-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes, Pharmaceutical Biology, 53:12, 1759-1767, DOI: 10.3109/13880209.2015 Results: The administration of D-GalN/LPS increased plasma aminotransferases (174.47 ± 4.5761 and 260.96 ± 1.9839 mkat/l) and total bilirubin levels (1.012 ± 0.0288 mg/dl), which were attenuated by C. myrrha treatment. Hepatic lipid peroxidation activity and nitric oxide content also increased, while the antioxidant activity measured by GSH (0.76 nmol/g protein), SOD (81.91 U/mg protein), and CAT (15.78 U/mg protein) was reduced. Commiphora myrrha provided significant restoration of GSH (0.815 nmol/gm protein), SOD (140.57 U/mg protein), and CAT (27.02 U/mg protein) levels. Furthermore, the acute phase response elicited by D-GalN/ LPS administration enhanced mRNA expressions of TNF-a, IL-6, IL-10, iNOS-2, and HO-1, which were ameliorated by C. myrrha treatment. Discussion and conclusion: These findings indicate that C. myrrha considerably reduces the oxidative stress of D-GalN/LPS-induced hepatic injury via multiple pathways including adown regulation of inflammatory mediators and cytokines. Such a property might be sufficient to combat cellular damage caused by various conditions that resemble fulminant hepatitis and could be of a potential clinical application.

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Section: Discussionmentioning

confidence: 80%

Hepatoprotective effect ofCommiphora myrrhaagainstd-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes

Ahmad

Raish

Ganaie

et al. 2015

Pharmaceutical Biology

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“…[11][12][13][14][15] In addition, hepatoprotective activities of S. chinensis have also been reported. [16][17][18][19] A recent study of ours showed that S. chinensis has a protective effect against ER stress-induced hepatic steatosis (unpublished data). S. chinensis contains various bioactive constituents, including lignans, triterpenoids, polysaccharides, and sterols.…”

mentioning

confidence: 66%

Protective Effect of Gomisin N against Endoplasmic Reticulum Stress-Induced Hepatic Steatosis

Jang

Yun

Kim

et al. 2016

Biological & Pharmaceutical Bulletin

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Gomisin N is a physiological substance derived from Schisandra chinensis. In the present study, the in vitro and in vivo effects of gomisin N on endoplasmic reticulum (ER) stress and hepatic steatosis were investigated. We quantified the expression of markers of ER stress, including glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein (C/EBP) homolog protein (CHOP), and X-box-binding protein-1 (XBP-1), and triglyceride (TG) accumulation, in HepG2 cells treated with tunicamycin or palmitate. Tunicamycin treatment in HepG2 cells induced expression of markers of ER stress and increased TG levels; Gomisin N reversed these effects, reducing the expression of markers of ER stress and TG levels. Similar effects were seen following palmitate pretreatment of HepG2 cells. The inhibitory effects of gomisin N were further confirmed in mice injected with tunicamycin. Gomisin N reduced expression of markers of ER stress and decreased TG levels in mouse liver after tunicamycin injection. Furthermore, gomisin N decreased expression of inflammatory and lipogenic genes in palmitate-incubated HepG2 cells. These results suggest that gomisin N inhibits ER stress and ameliorates hepatic steatosis induced by ER stress. Key words gomisin N; endoplasmic reticulum (ER) stress; hepatic steatosis; lipogenesis; inflammationThe endoplasmic reticulum (ER) plays critical roles in the synthesis of secreted and membrane proteins by mediating protein folding, production of lipids and sterols, and the storage of intracellular Ca 2+ . 1) However, pathological factors that disrupt ER homeostasis lead to the accumulation of unfolded protein in the ER lumen, provoking ER stress. Cells usually survive early stress by attenuating protein translation, removing unfolded proteins, and upregulating protein chaperons via the unfolded protein response (UPR).1) However, prolonged ER stress can lead to cell death and cause several diseases including ischemia/reperfusion injury, heart disease, and diabetes. [2][3][4][5] Recent studies show that hepatic ER stress is observed in metabolic diseases such as obesity and diabetes.2-5) ER stress contributes to development of insulin resistance and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). [6][7][8][9]

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“…Several studies have demonstrated the diverse pharmacological activities of S. chinensis, which include anti-oxidant, anti-tumor, anti-obesity, anti-inflammatory, and cardioprotective effects [4-6, 15, 19]. In addition, hepatoprotective activities of S. chinensis have also been reported [8,9,14,25]. S. chinensis contains various bioactive constituents, including lignans, triterpenoids, polysaccharides, and sterols [10].…”

Section: Introductionmentioning

confidence: 99%

Gomisin A Ameliorates Endoplasmic Reticulum Stress-induced Hepatic Steatosis

Yun¹,

Jung²

2017

Journal of Life Science

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Previously, we have shown that Schisandra chinensis (Turcz.) Baill. (S. chinensis) has a protective effect against endoplasmic reticulum (ER) stress-induced hepatic steatosis. Gomisin A is a bioactive phytoestrogen derived from S. chinensis. In the present study, the in vitro and in vivo effects of gomisin A on ER stress and hepatic steatosis were investigated. We quantified the expression of markers of ER stress, including glucose regulated protein 78 (GRP78), C/EBP homolog protein (CHOP), and X-boxbinding protein-1 (XBP-1), in HepG2 cells treated with tunicamycin or palmitate. Tunicamycin treatment in HepG2 cells induced the expression of markers of ER stress, including GRP78, CHOP, and XBP-1c. However, treatment with gomisin A reduced the expression of markers of ER stress. These inhibitory effects were also observed in palmitate-incubated HepG2 cells. The in vivo inhibitory effects of gomisin A were assessed in mice injected with tunicamycin or fed with a high fat diet (HFD). Gomisin A reduced the expression of markers of ER stress and decreased triglyceride levels in the livers of mice after tunicamycin injection or HFD feeding. Furthermore, gomisin A decreased the expression of inflammatory genes in palmitate-incubated HepG2 cells and the liver of HFD-fed obese mice. These results suggest that gomisin A inhibits ER stress and ameliorates hepatic steatosis induced by ER stress.

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Anti-apoptotic and Hepatoprotective Effects of Gomisin A on Fulminant Hepatic Failure Induced by D-Galactosamine and Lipopolysaccharide in Mice

Cited by 59 publications

References 31 publications

Hepatoprotective effect ofCommiphora myrrhaagainstd-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes

Hepatoprotective effect ofCommiphora myrrhaagainstd-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes

Protective Effect of Gomisin N against Endoplasmic Reticulum Stress-Induced Hepatic Steatosis

Gomisin A Ameliorates Endoplasmic Reticulum Stress-induced Hepatic Steatosis

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