The inhibition of apoptosis by glycyrrhizin in hepatic injury induced by injection of lipopolysaccharide / D-galactosamine in mice

Ikeda, Tadayuki; Abe, Kazuki; Kuroda, Noriyuki; Kida, Yujiro; Inoue, Hideo; Wake, Kanako; Morito, Mitsuhiko; Sato, Toshio

doi:10.1679/aohc.71.163

Cited by 20 publications

(24 citation statements)

References 38 publications

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“…The injection of LPS/GalN signiicantly increases serum AST and ALT activities as compared with controls. The enhancement of AST and ALT levels is signiicantly suppressed by an intraperitoneal administration of GL (Figure 1; [19,37,38]). Administration of LPS/GalN precipitate tissue injury associated with time-dependent alteration in HMGB1 serum levels.…”

Section: Resultsmentioning

confidence: 96%

Novel Mechanism Supporting Therapeutic Effects of Glycyrrhizin in Acute or Chronic Hepatitis

Kuroda¹,

Sato²

2017

Biological Activities and Action Mechanisms of Licorice Ingredients

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Glycyrrhizin (GL) isolated from the roots of licorice plant (Glycyrrhiza glabra L.) has been traditionally used for treating peptic ulcer, hepatitis, and pulmonary bronchitis. In addition to the protective efects of GL against liver injury or cancer proliferation by the membrane stabilization or via progesterone-receptor membrane component 1 (PGRMC1), the present chapter reports its new therapeutic mechanism through high-mobility group protein 1 (HMGB1) to which GL directly binds. In this study, we evaluated inlammation-promoting activity of HMGB1 and blockade of extracellular release of HMGB1 by GL in lipopolysaccharide (LPS)/d-galactosamine (GalN)-triggered mouse liver injury. In this experimental hepatitis model, apoptotic response of hepatocytes through the binding of HMGB1 protein to Glutathione transferase omega 1 (Gsto1), an apoptosis-associated gene, promoter region is caused, serum AST and ALT activities signiicantly increased, and GL-treatment prevented the apoptosis and inlammatory iniltrates induced with LPS/GalN-injection by disturbing the binding of HMGB1 protein to Gsto1 promoter sequence. Analysis with chromatin immunoprecipitation (ChIP)-assay revealed inhibiting the binding of HMGB1 protein to Gsto1 by the binding of GL to HMGB1.

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Section: Resultsmentioning

confidence: 96%

Novel Mechanism Supporting Therapeutic Effects of Glycyrrhizin in Acute or Chronic Hepatitis

Kuroda¹,

Sato²

2017

Biological Activities and Action Mechanisms of Licorice Ingredients

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“…28, 29 It has been suggested that glycyrrhizin possibly acts as a radical scavenger in the cytoplasm of hepatocytes and decreases cell membrane permeability. 17 A previous report has shown that intravenous glycyrrhizin can effectively protect liver against fulminant hepatic failure induced by lipopolysaccharide/ d -galactosamine in mice, and that glycyrrhizin prevents hepatocytes' apoptosis by inhibiting inflammatory reaction and stabilizing mitochondria membrane to suppress the release of cytochrome C and sequential activation of caspase-3.…”

Section: Discussionmentioning

confidence: 99%

A Randomized Controlled Trial of Glycyrrhizin Plus Tenofovir vs. Tenofovir in Chronic Hepatitis B with Severe Acute Exacerbation

Hung

Kee

Chen

et al. 2017

Clinical and Translational Gastroenterology

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Objectives:Severe acute exacerbation (SAE) of chronic hepatitis B (CHB) may progress to liver failure with high potential mortality despite the prompt treatment with nucleos(t)ide analogs. This study aimed to evaluate the efficacy and safety of glycyrrhizin in the treatment of CHB with SAE.Methods:Sixty patients with SAE of CHB were randomly treated with tenofovir plus intravenous glycyrrhizin (group A, n=30) or with tenofovir alone (group B, n=30). Primary end points were the improvement of serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and model for end-stage liver disease (MELD) score. Secondary end point was overall mortality or receipt of liver transplantation by week 24.Results:Patients in group A had significant reductions of serum AST and ALT levels from baseline at days 3, 5, 8, and 15 than those in group B (all P<0.05). The MELD score significantly decreased since week 1 in the group A patients, whereas there were no changes relative to baseline in group B patients at weeks 1 and 2. By week 24, one (3.3%) of group A patients and four (13.3%) of group B patients died (n=3) or received liver transplantation (n=1) (P=0.177). Multivariate analysis identified baseline MELD score (P=0.021) as an independent factor for mortality or receipt of liver transplantation. There were no differences in the rates of grade 3 hypertension, hypokalemia and ascites between two groups.Conclusions:Early introduction of glycyrrhizin can be safe and helpful for patients with SAE of CHB.

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“…Yang et al reported that pre-treatment of intravenous glycyrrhizin (Stronger Neo-Minophagen C, SNMC) can effectively protect liver against fulminant hepatic failure induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal N) in mice, and that SNMC prevents hepatocyte apoptosis by inhibiting inflammatory reaction and stabilizing mitochondria membrane to suppress the release of cytochrome C and sequential activation of caspase-3 [22]. Ikeda et al reported that glycyrrhizin inhibited the apoptosis of liver cells through the prevention of an IL-18-mediated inflammatory response in a caspase-independent manner in LPS/D-GalNinduced mouse liver injury [23].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Intravenous Glycyrrhizin in the Early Stage of Acute Onset Autoimmune Hepatitis

et al. 2011

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The inhibition of apoptosis by glycyrrhizin in hepatic injury induced by injection of lipopolysaccharide / D-galactosamine in mice

Abstract: Summary. The inhibition of apoptosis by glycyrrhizin (GL) in hepatic injury induced by injection of lipopolysaccharide (LPS)/D-galactosamine (D-GalN

Cited by 20 publications

References 38 publications

Novel Mechanism Supporting Therapeutic Effects of Glycyrrhizin in Acute or Chronic Hepatitis

Novel Mechanism Supporting Therapeutic Effects of Glycyrrhizin in Acute or Chronic Hepatitis

A Randomized Controlled Trial of Glycyrrhizin Plus Tenofovir vs. Tenofovir in Chronic Hepatitis B with Severe Acute Exacerbation

Efficacy of Intravenous Glycyrrhizin in the Early Stage of Acute Onset Autoimmune Hepatitis

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