Improvement of selectivity and sensitivity by column switching in the determination of glycyrrhizin and glycyrrhetic acid in human plasma by high-performance liquid chromatography

Groot, Gerard de; Koops, Reinder; Hogendoorn, E.A.; Goewie, C.E.; Jean, T.; Savelkoul, F.; Vloten, Piet van

doi:10.1016/0021-9673(86)80007-3

Cited by 45 publications

(24 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intravenous administration of GL in healthy men and in hepatitis C patients achieved maximal plasma concentrations of 29 g/ml (approx 36 M) (52) and 120 M (53), respectively, whereas orally administered GL yielded no detectable plasma GL and only very low (Ͻ200 ng/ml) concentrations of GA (52). In another study, plasma GA levels reached 10 M in humans ingesting licorice (54), similar to the protective concentrations of GA in our study.…”

Section: Discussionsupporting

confidence: 85%

Licorice Compounds Glycyrrhizin and 18β-Glycyrrhetinic Acid Are Potent Modulators of Bile Acid-induced Cytotoxicity in Rat Hepatocytes

Gumpricht

Dahl

Devereaux

et al. 2005

Journal of Biological Chemistry

125

View full text Add to dashboard Cite

The accumulation of hydrophobic bile acids results in cholestatic liver injury by increasing oxidative stress, mitochondrial dysfunction, and activation of cell signaling pathways. Licorice root and its constituents have been utilized as antihepatotoxic agents. The purpose of this study was to evaluate the potential modulation by a primary component of licorice root, glycyrrhizin (GL), and its metabolite, 18␤-glycyrrhetinic acid (GA), in a hepatocyte model of cholestatic liver injury. Preincubation of fresh rat hepatocyte suspensions with GL or GA reduced glycochenodeoxycholic acid (GCDC)-dependent reactive oxygen species generation, with GA more potent than GL. Interestingly, GL and GA had opposing effects toward GCDC-induced cytotoxicity; GA prevented both necrosis and apoptosis, whereas GL enhanced apoptosis. GCDC promoted activation of caspase 10, caspase 3, and PARP; all were inhibited by GA but not GL. Induction of apoptosis by GCDC was also associated with activation of JNK, which was prevented by GA. Activation of caspase 9 and dissipation of mitochondrial membrane potential were prevented by GA but not GL. In liver mitochondrial studies, GL and GA were both potent inhibitors of the mitochondrial permeability transition, reactive oxygen species generation, and cytochrome c release at submicromolar concentrations. Results from this study suggest that GL exhibits proapoptotic properties, whereas GA is a potent inhibitor of bile acid-induced apoptosis and necrosis in a manner consistent with its antioxidative effect.

show abstract

Section: Discussionsupporting

confidence: 85%

Licorice Compounds Glycyrrhizin and 18β-Glycyrrhetinic Acid Are Potent Modulators of Bile Acid-induced Cytotoxicity in Rat Hepatocytes

Gumpricht

Dahl

Devereaux

et al. 2005

Journal of Biological Chemistry

125

View full text Add to dashboard Cite

show abstract

“…16) In conclusion, we provide evidence that GA is capable of effectively killing tumor cells in the CNS, that adhesion loss caused by GA is fatal and irreversible, and that GA induces cytoskeletal disruption and anoikis-like death. Further, the GA content in licorice has been reported to be 5.8 to 11.4%, 17) and plasma GA levels reached 10 mM in humans ingesting licorice, 18) which is exactly the same concentration that affected the tumor cells effectively in the present study. Although validation studies supporting the utilization in clinical practice are warranted, a licorice compound GA, that could disturb cytoskeletons and adhesion, may potentiate anticancer effects on the anoikis-prone cells.…”

Section: Resultssupporting

confidence: 73%

Glycyrrhetinic Acid Induces Anoikis-Like Death and Cytoskeletal Disruption in the Central Nervous System Tumorigenic Cells

Yamaguchi

Kidachi

Kamiie

et al. 2010

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Licorice extracts and the principal licorice component glycyrrhizin (GL) are used worldwide in foods, tobacco and medicines. The sweet taste of licorice roots arises from GL, which is reputed to be at least 50 times sweeter than refined sugar. Owing to this sweetness, GL is extensively used as a natural sweetener and flavoring additive.1) GL is a saponin compound comprising a triterpenoid aglycone, glycyrrhetinic acid (GA), conjugated to a disaccharide of glucuronic acid. GA is used as an antitoxic and immunological regulatory agent for the prevention or treatment of viral infection, inflammation and anaphylaxis.2,3) However, despite its wide use in the market and great effects on some physiological aspects, to the best of our knowledge, no studies have investigated the antitumor effects of GA on tumor cells in the central nervous system (CNS).Serum-free mouse embryo (SFME) cells were originally derived from a 16-d-old whole Balb/c mouse embryo and are maintained in a serum-free culture medium.4) These cells do not undergo growth crisis, maintain their diploid karyotype for extended passages and are non-tumorigenic in vivo. Consequently, they are non-transformed, behave as primary cultures, have a finite lifespan and display the characteristics of CNS progenitor cells.5,6) SFME cells were cotransfected with the human c-Ha-ras and mouse c-myc genes, and the resulting cells were designated ras/myc SFME cells. 7) While SFME cells are non-tumorigenic in vivo, 5,6) ras/myc SFME cells are tumorigenic and do not require any growth factors, such as epidermal growth factor. 7) Another line of SFME-derived tumorigenic cells are highly metastatic ras/myc SFME-1 (r/m HM-SFME-1) cells, which were established by selecting ras/myc SFME cells that only metastasize to the lungs of Balb/c mice. 8) In the present study, r/m HM-SFME-1 cells were treated with GA and its efficacy as an antitumor agent through anoikis-like cell death and cytoskeletal disruption was investigated. Cell Culture SFME and r/m HM-SFME-1 cells were cultured in a humidified 5% CO 2 -95% air atmosphere at 37°C in 60 mm diameter dishes, pre-coated with 10 mg/ml fibronectin. The basal nutrient culture medium was a 1 : 1 mixture of Dulbecco's modified Eagle's medium and Ham's F12 9,10) containing 15 mM N-(2-hydroxyethyl)piperazine-NЈ-2-ethanesulfonic acid (HEPES), pH 7.4, 1.2 mg/ml sodium bicarbonate, 10 nM sodium selenite and 10 mg/ml gentamicin, supplemented with insulin (10 mg/ml), transferrin (25 mg/ml) and epidermal growth factor (50 ng/ml). Cell passages were accomplished by rapid trypsinization with 0.2% crude trypsin and 1 mM ethylenediaminetetraacetate in phosphatebuffered saline (PBS) without calcium or magnesium, followed by dilution in the culture medium at room temperature. The medium containing the collected cells was centrifuged at 250 g at 4°C for 7 min and the supernatant was removed. The cells were suspended in the culture medium without the supplements, plated at 1ϫ10 5 cells/dish and cultured again in the medium with the supplements. Following...

show abstract

“…In patients with chronic hepatitis, the administration with GL suppository (a mixture of 300 mg glycyrrhizinic ammonium salt and 60 g of sodium capric acid) yielded approximately 6 M serum GL levels (Fujioka et al, 2003). Orally administered licorice achieved 0.4 to 10 M plasma GA levels in humans (de Groot et al, 1988;Yamamura et al, 1992). The current work was performed under acute exposure to high concentration of MPP ϩ .…”

Section: Discussionmentioning

confidence: 95%

Protective Effect of Glycyrrhizin on 1-Methyl-4-phenylpyridinium-Induced Mitochondrial Damage and Cell Death in Differentiated PC12 Cells

Yim¹,

Park²,

Lee³

2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Defects in mitochondrial function have been shown to participate in the induction of neuronal cell injury. The aim of the present study was to assess the preventive effect of licorice compounds glycyrrhizin and 18␤-glycyrrhetinic acid against the toxicity of parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP ϩ ) in relation to the mitochondria-mediated cell death process and role of oxidative stress. MPP ϩ induced the nuclear damage, the changes in the mitochondrial membrane permeability, leading to the cytochrome c release and caspase-3 activation, the formation of reactive oxygen species, and the depletion of glutathione (GSH) in differentiated PC12 cells. Glycyrrhizin up to 100 M significantly attenuated cell death and depletion of GSH due to MPP ϩ concentration-dependently. Meanwhile, 18␤-glycyrrhetinic acid showed a maximal inhibitory effect at 10 M; beyond this concentration, the inhibitory effect declined. The protective effect of licorice compounds was also detected in the rotenone-treated PC12 cells. Glycyrrhizin and 18␤-glycyrrhetinic acid prevented the MPP ϩ -induced formation of the mitochondrial permeability transition. The results show that both glycyrrhizin and a metabolite, 18␤-glycyrrhetinic acid, exhibit a depressant effect against the MPP ϩ toxicity. Glycyrrhizin and 18␤-glycyrrhetinic acid may prevent the cytotoxicity of MPP ϩ by suppressing the mitochondrial permeability transition formation. The preventive effect seems to be ascribed to the inhibitory effect on the formation of reactive oxygen species and depletion of GSH.Mitochondrial dysfunction and increased oxidative stress have been shown to be implicated in dopaminergic cell degeneration in Parkinson's disease (Jenner, 2003). In this disease, the major mitochondrial defect seems to be associated with complex I at the electron transport chain. Impairment of complex I activity leads to excess ROS formation, which causes mitochondrial dysfunction and cell death (Fleury et al., 2002;Jenner, 2003). Implication of oxidative stress in the pathogenesis and progression of Parkinson's disease is supported by the decrease in GSH content, increase in levels of lipid peroxidation products, increased production of ROS, and increase in iron content in substantia nigra (Olanow and Tatton, 1999).MPTP produces an irreversible and severe parkinsonianlike syndrome in human and nonhuman primates (Przedborski and Jackson- Lewis, 1998;Przedborski et al., 2000). The inhibition of complex I in the mitochondrial electron transport chain induced by MPP ϩ , the active metabolite of MPTP, results in impaired ATP production, loss of mitochondrial membrane potential, and formation of ROS (Cassarino et al., 1997;Schulz et al., 1997). The membrane permeability transition of mitochondria is known as a central event in the course of toxic and oxidative forms of cell injury, as well as apoptosis (Mignotte and Vayssière, 1998). Along with respiratory chain inhibition, MPP ϩ -induced neuronal cell death is suggested to be mediated by formation of the mitocho...

show abstract

Improvement of selectivity and sensitivity by column switching in the determination of glycyrrhizin and glycyrrhetic acid in human plasma by high-performance liquid chromatography

Cited by 45 publications

References 4 publications

Licorice Compounds Glycyrrhizin and 18β-Glycyrrhetinic Acid Are Potent Modulators of Bile Acid-induced Cytotoxicity in Rat Hepatocytes

Licorice Compounds Glycyrrhizin and 18β-Glycyrrhetinic Acid Are Potent Modulators of Bile Acid-induced Cytotoxicity in Rat Hepatocytes

Glycyrrhetinic Acid Induces Anoikis-Like Death and Cytoskeletal Disruption in the Central Nervous System Tumorigenic Cells

Protective Effect of Glycyrrhizin on 1-Methyl-4-phenylpyridinium-Induced Mitochondrial Damage and Cell Death in Differentiated PC12 Cells

Contact Info

Product

Resources

About