Use of glycyrrhizin in prevention of tissue damage caused by ischemia-reperfusion in rabbit hind limbs

Nakata, Nobuaki; Takaoka, Kunio

doi:10.1007/s00776-006-1027-8

Cited by 5 publications

(4 citation statements)

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“…7) The clinical dose and administration method of fondaparinux are 5-7.5 mg/day and a subcutaneous injection, respectively, and its dose was 0.2 mg/kg (subcutaneous injection) in a study on intestinal ischemia-reperfusion in rats by Olanders et al,26) suggesting that the dose (1.5 mg/kg) administered to rats in our study was comparatively high for animal experiments. 'Inflammation' and venous thrombosis are cross-linked.…”

Section: Discussionmentioning

confidence: 57%

“…10) Glycyrrhizin, an agent with a chemical structure analogous to that of sialyl-Lewis X and the ability to bind P-and L-selectins, may be useful for blocking the P-selectinmediated thrombotic cascade due to its competitive binding to sialyl-Lewis X oligosaccharides on neutrophils and subsequent blocking of neutrophil adhesion to the vascular endothelium. 7,11) …”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 57%

mentioning

confidence: 99%

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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“…A recent study displayed that SNMC exerted neuroprotective effects through suppressing microglia activation and neutrophil infiltration in the ischemic brain in MCAO rats [ 91 ]. GL was potentially useful for inflammatory response by suppressing the adherence of neutrophils to the vascular endothelium [ 97 – 99 ], with evidence of reduced activity of myeloperoxidase (MPO) [ 100 , 101 ].…”

Section: Natural Components From Medicinal Plants Inhibiting Neutrmentioning

confidence: 99%

Anti-Inflammation of Natural Components from Medicinal Plants at Low Concentrations in Brain via Inhibiting Neutrophil Infiltration after Stroke

Chen

Zhang

et al. 2016

Mediators of Inflammation

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Inflammation after stroke consists of activation of microglia/astrocytes in situ and infiltration of blood-borne leukocytes, resulting in brain damage and neurological deficits. Mounting data demonstrated that most natural components from medicinal plants had anti-inflammatory effects after ischemic stroke through inhibiting activation of resident microglia/astrocytes within ischemic area. However, it is speculated that this classical activity cannot account for the anti-inflammatory function of these natural components in the cerebral parenchyma, where they are detected at very low concentrations due to their poor membrane permeability and slight leakage of BBB. Could these drugs exert anti-inflammatory effects peripherally without being delivered across the BBB? Factually, ameliorating blood-borne neutrophil recruitment in peripheral circulatory system has been proved to reduce ischemic damage and improve outcomes. Thus, it is concluded that if drugs could achieve effective concentrations in the cerebral parenchyma, they can function via crippling resident microglia/astrocytes activation and inhibiting neutrophil infiltration, whereas the latter will be dominating when these drugs localize in the brain at a low concentration. In this review, the availability of some natural components crossing the BBB in stroke will be discussed, and how these drugs lead to improvements in stroke through inhibition of neutrophil rolling, adhesion, and transmigration will be illustrated.

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“…Further, glycyrrhizin has numerous other protective pharmacological functions, like anti-ulcer and anti-allergic effects (reviewed in the literature [ 12 , 13 ]). Glycyrrhizin has anti-viral effects in vitro and it dampens inflammatory reactions in various animal models [ 14 , 15 , 16 , 17 , 18 , 19 ]. Anti-inflammatory effects of glycyrrhizin are at least partly due to its ability to downregulate proinflammatory cytokine expression and inhibit leukocyte diapedesis.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Homophilic Interactions and Ligand Binding of the Receptor for Advanced Glycation End Products by Heparin and Heparin-Related Carbohydrate Structures

et al. 2018

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Background: Heparin and heparin-related sulphated carbohydrates inhibit ligand binding of the receptor for advanced glycation end products (RAGE). Here, we have studied the ability of heparin to inhibit homophilic interactions of RAGE in living cells and studied how heparin related structures interfere with RAGE–ligand interactions. Methods: Homophilic interactions of RAGE were studied with bead aggregation and living cell protein-fragment complementation assays. Ligand binding was analyzed with microwell binding and chromatographic assays. Cell surface advanced glycation end product binding to RAGE was studied using PC3 cell adhesion assay. Results: Homophilic binding of RAGE was mediated by V1- and modulated by C2-domain in bead aggregation assay. Dimerisation of RAGE on the living cell surface was inhibited by heparin. Sulphated K5 carbohydrate fragments inhibited RAGE binding to amyloid β-peptide and HMGB1. The inhibition was dependent on the level of sulfation and the length of the carbohydrate backbone. α-d-Glucopyranosiduronic acid (glycyrrhizin) inhibited RAGE binding to advanced glycation end products in PC3 cell adhesion and protein binding assays. Further, glycyrrhizin inhibited HMGB1 and HMGB1 A-box binding to heparin. Conclusions: Our results show that K5 polysaccharides and glycyrrhizin are promising candidates for RAGE targeting drug development.

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Use of glycyrrhizin in prevention of tissue damage caused by ischemia-reperfusion in rabbit hind limbs

Cited by 5 publications

References 20 publications

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

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

Anti-Inflammation of Natural Components from Medicinal Plants at Low Concentrations in Brain via Inhibiting Neutrophil Infiltration after Stroke

Inhibition of Homophilic Interactions and Ligand Binding of the Receptor for Advanced Glycation End Products by Heparin and Heparin-Related Carbohydrate Structures

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