Attenuation of Dysfunction in the Ischemia-Reperfused Liver by Glycyrrhizin.

Nagai, Takayuki; Egashira, Toru; Kudo, Yoshikuni; Yamanaka, Yasumitsu; Shimada, Toshio

doi:10.1254/jjp.58.209

Cited by 38 publications

(30 citation statements)

References 22 publications

(15 reference statements)

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“…Figure 4 showed the FTIR spectra of micelles and DG. According to the literature, 17 the peak of 1579 cm 21 in Figure 4(A) was attributed to the linkage of phosphoric and ammonium ions in DG-unloaded mPIC micelles. Compared to the spectrum of DG alone [ Fig.…”

Section: Physicochemical Characterization Of Dg-loaded Micellesmentioning

confidence: 69%

See 1 more Smart Citation

Novel polyion complex micelles for liver‐targeted delivery of diammonium glycyrrhizinate: In vitro and in vivo characterization

Yang

Zhuo

et al. 2008

J Biomedical Materials Res

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Polyion complex micelles (PIC micelles) based on methoxy poly(ethylene glycol)-grafted-chitosan (mPEG-g-Chitosan) and lactose-conjugated PEG-grafted-chitosan (Lac-PEG-g-Chitosan) were designed as carriers for anionic drugs. Diammonium glycyrrhizinate (DG)-loaded conventional PIC micelles (mPIC micelles) and lactose-modified PIC micelles (Lac-PIC micelles) were prepared successfully with encapsulation efficiency of 97.4% and 96.7%, respectively. These micelles were uniform spherical particles with a mean size of 21.6 and 26.4 nm by transmission electron microscopy, respectively. No significant size change of these micelles in three months indicated their good physical stability. The in vitro drug release behavior of mPIC micelles in different media as well as the changes of size and zeta potential demonstrated that the drug was released mainly through swelling and diffusion induced by ion exchange. The pharmacokinetic experiments showed that the area under the curve of DG plasma concentration-time profile in rats for mPIC micelles and Lac-PIC micelles were 1.2 times and 0.4 times higher than that for DG injection, respectively. The liver targeting ability of both mPIC micelles and Lac-PIC micelles was evaluated in rats, revealing that Lac-PIC micelles could deliver more DG to liver than mPIC micelles. Therefore, the Lac-PIC micelles prepared in this study were promising liver-targeted nanocarriers for DG.

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Section: Physicochemical Characterization Of Dg-loaded Micellesmentioning

confidence: 69%

“…Glycyrrhizin possesses various pharmacological effects, including anti-inflammatory, 19 antiviral, 20 and antioxidative activities. 21 It has been clinically used as a remedy for the treatment of chronic hepatitis 22 and immunodeficiency virus infection.…”

Section: Introductionmentioning

confidence: 99%

Novel polyion complex micelles for liver‐targeted delivery of diammonium glycyrrhizinate: In vitro and in vivo characterization

Yang

Zhuo

et al. 2008

J Biomedical Materials Res

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“…Furthermore, glycyrrhizin reduces I/R-induced liver injury (Nagai et al, 1992) and inhibits elevated circulating levels of HMGB1 in the acute phase (Mabuchi et al, 2009). Accordingly, the purpose of this study was to investigate the effect of glycyrrhizin on liver injury caused by I/R and the production of HMGB1 by Kupffer cells in rats.…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizin Prevents Liver Injury by Inhibition of High-Mobility Group Box 1 Production by Kupffer Cells after Ischemia-Reperfusion in Rats

Ogiku

Kono²,

Hara³

et al. 2011

J Pharmacol Exp Ther

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High-mobility group box 1 (HMGB1) acts as an early mediator of inflammation and organ damage in hepatic ischemia-reperfusion (I/R) injury. Glycyrrhizin is a natural anti-inflammatory and antiviral triterpene in clinical use. The purpose of this study was to investigate the effect of glycyrrhizin on liver injury caused by I/R and production of HMGB1 by Kupffer cells in rats. In the first test period, rats were given saline or glycyrrhizin 20 min before segmental hepatic warm I/R. Serum alanine aminotransferase and HMGB1 levels and hepatic histopathological findings were evaluated after I/R. Furthermore, expression of HMGB1 in the liver was assessed by immunohistochemical staining after I/R. Kupffer cells were isolated by collagenase digestion and differential centrifugation, and production of HMGB1 was assessed. In another set of experiments, the effect of inhibition of Kupffer cells by injection of liposome-entrapped dichloromethylene diphosphonate (lipo-MDP) on liver injury and expression of HMGB1 were investigated after I/R. Liver injury was prevented in the glycyrrhizin group compared with the control group. Furthermore, serum HMGB1 levels were also significantly blunted in the glycyrrhizin group compared with the control group. Cells expressing HMGB1 were detected in the hepatic sinusoid by immunohistochemistry and recognized morphologically as Kupffer cells. Furthermore, the expression of HMGB1 was reduced in the glycyrrhizin group compared with the control group. Production of HMGB1 was reduced in Kupffer cells isolated from the glycyrrhizin group compared with the control group. It is noteworthy that treatment with lipo-MDP significantly blunted serum HMGB1 levels and prevented liver injury after I/R. These results suggest that glycyrrhizin has the therapeutic potential to prevent warm I/R-induced injury during hepato-biliary surgery.

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“…The plasma concentration of intravenously injected glycyrrhizin was previously shown to peak during the 10 min following its injection and then declined, but was still detectable in the subsequent 10 h; 25) therefore, glycyrrhizin may inhibit the adherence of neutrophils by binding to P-selectin within several hours of IVC ligation.…”

Section: Discussionmentioning

confidence: 92%

Effects of Preoperative Glycyrrhizin Infusion for the Prevention of Venous Thrombosis on the Tissue Expression of Antithrombin in a Rat Model

Nakata¹,

Kira

2016

Annals of Vascular Diseases

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Objective: Using a thrombus model prepared by ligation of the inferior vena cava (IVC), the influences of the glycoside, glycyrrhizin, on plasma antithrombin levels and antithrombin mRNA expression levels in the liver and IVC with the inhibition of venous thrombosis were investigated. Materials and Methods: The rat IVC was exposed and ligated for 24 h immediately after the intravenous administration of 300 mg/kg glycyrrhizin. Among antithrombotic drugs, the Xa inhibitor, fondaparinux sodium, was used as a control drug. Results: The mean thrombus weight was significantly smaller in the glycyrrhizin-treated group (18.3 mg) than in the salinetreated group (34.3 mg). In contrast, the inhibition of thrombosis was not observed in the fondaparinux-treated group. Antithrombin mRNA expression levels in the liver were significantly higher in the ligated groups than in the baseline control group. The mean plasma antithrombin level was significantly lower in the glycyrrhizin group (96.6%) than in the saline group (114.4%), but was not significantly different from that in the baseline control group (102.4%). Conclusion:The pretreatment with glycyrrhizin inhibited venous thrombosis, and antithrombin mRNA expression levels in the liver and IVC as well as plasma antithrombin levels were significantly lower than those in the saline group.Keywords: glycyrrhizin, antithrombin, DVT targets being thrombin, factor Xa, and factor IXa. A sequence-specific pentasaccharide present in only a fraction of heparin molecules mediates the high-affinity binding and anticoagulant activation of antithrombin by this polysaccharide. 1) Antithrombin has lysine binding sites to which heparin binds at a molar ratio of 1:1. The half-life of thrombin is reduced to 20 ms in the presence of a high concentration of heparin, which is an approximately 2000-fold acceleration of this reaction. 2) Griffith previously identified thrombin-heparin binding as the most important factor for efficient thrombin inhibition by antithrombin. 3) P-and E-selectins have been known to mediate the linkage of endothelial cells to neutrophils through the binding to sialyl-Lewis X glycoproteins, which are expressed on the surface of neutrophils. 4,5) Neutrophils adherent to the endothelium also undergo transendothelial migration, leading to endothelial cell sloughing and exposure of the underlying basement membrane to the accelerated formation of deep vein thrombosis (DVT). 6) Glycyrrhizin, which is a natural triterpenoid saponin with a molecular mass of 840 Daltons, has been approved for useful drug for the treatment of allergic disorders and chronic hepatitis in Japan. We previously showed that glycyrrhizin was effective on the prevention of the tissue damage caused by ischemia-reperfusion in the rabbit hind limb. 7) were the first to demonstrate that glycyrrhizin exhibits antithrombotic activity in vivo and, it has, thus, been characterized as a potential thrombin inhibitor. Assafim et al. 9) showed that glycyrrhizin was effective in preventing venom-induced thrombus formati...

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Attenuation of Dysfunction in the Ischemia-Reperfused Liver by Glycyrrhizin.

Cited by 38 publications

References 22 publications

Novel polyion complex micelles for liver‐targeted delivery of diammonium glycyrrhizinate: In vitro and in vivo characterization

Novel polyion complex micelles for liver‐targeted delivery of diammonium glycyrrhizinate: In vitro and in vivo characterization

Glycyrrhizin Prevents Liver Injury by Inhibition of High-Mobility Group Box 1 Production by Kupffer Cells after Ischemia-Reperfusion in Rats

Effects of Preoperative Glycyrrhizin Infusion for the Prevention of Venous Thrombosis on the Tissue Expression of Antithrombin in a Rat Model

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