BACKGROUND Acetaminophen overdose is the most frequent cause of drug-induced liver failure in developed countries.Substantial progress has been made in understanding the mechanism of hepatocellular injury,but N-acetyl...BACKGROUND Acetaminophen overdose is the most frequent cause of drug-induced liver failure in developed countries.Substantial progress has been made in understanding the mechanism of hepatocellular injury,but N-acetylcysteine remains the only effective treatment despite its short therapeutic window.Thus,other hepatoprotective drugs are needed for the delayed treatment of acetaminopheninduced hepatotoxicity.Our interest focused on glycyrrhizin for its role as an inhibitor of high mobility group box 1(HMGB1)protein,a member of the family of damage-associated molecular pattern,known to play an important pathological role in various diseases.AIM To investigate the efficacy of the N-acetylcysteine/glycyrrhizin combination compared to N-acetylcysteine alone in the prevention of liver toxicity.METHODS Eight-week-old C57BL/6J wild-type female mice were used for all our experiments.Mice fasted for 15 h were treated with acetaminophen(500 mg/kg)or vehicle(phosphate-buffered saline)by intraperitoneal injection and separated into the following groups:Glycyrrhizin(200 mg/kg);N-acetylcysteine(150 mg/kg);and N-acetylcysteine/glycyrrhizin.In all groups,mice were sacrificed 12 h following acetaminophen administration.The assessment of hepatotoxicity was performed by measuring plasma levels of alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase.Hepatotoxicity was also evaluated by histological examination of hematoxylin and eosin-stained tissues sections.Survival rates were compared between various groups using Kaplan-Meier curves.RESULTS Consistent with data published in the literature,we confirmed that intraperitoneal administration of acetaminophen(500 mg/kg)in mice induced severe liver injury as evidenced by increases in alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase but also by liver necrosis score.Glycyrrhizin administration was shown to reduce the release of HMGB1 and significantly decreased the severity of liver injury.Thus,the co-administration of glycyrrhizin and N-acetylcysteine was investigated.Administered concomitantly with acetaminophen,the combination significantly reduced the severity of liver injury.Delayed administration of the combination of drugs,2 h or 6 h after acetaminophen,also induced a significant decrease in hepatocyte necrosis compared to mice treated with N-acetylcysteine alone.In addition,administration of N-acetylcysteine/glycyrrhizin combination was associated with an improved survival rate compared to mice treated with only N-acetylcysteine.CONCLUSION We demonstrate that,compared to N-acetylcysteine alone,co-administration of glycyrrhizin decreases the liver necrosis score and improves survival in a murine model of acetaminophen-induced liver injury.Our study opens a potential new therapeutic pathway in the prevention of acetaminophen hepatotoxicity.展开更多
AIM:To examine the efficacy of glycyrrhizin preparation(GL-p) in the treatment of a rat model of ulcerative colitis(UC).METHODS:Experimental colitis was induced by oral administration of dextran sodium sulfate.Rats wi...AIM:To examine the efficacy of glycyrrhizin preparation(GL-p) in the treatment of a rat model of ulcerative colitis(UC).METHODS:Experimental colitis was induced by oral administration of dextran sodium sulfate.Rats with colitis were intrarectally administered GL-p or saline.The extent of colitis was evaluated based on body weight gain,colon wet weight,and macroscopic damage score.The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis.The effect of GL-p on myeloperoxidase(MPO) activity in the inflamed mucosa and purified enzyme was assayed.RESULTS:GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline.Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines,including interleukin(IL)-1β,IL-6,tumor necrosis factor-α,cytokine-induced neutrophil chemoattractant-2,and monocyte chemoattractant protein-1 in the inflamed mucosa.Furthermore,GL-p inhibited the oxidative activity of mucosal and purified MPO.CONCLUSION:GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.展开更多
Objective:To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rate.Methods:A total of 75 SD rate were randomly divided into A,B,C,D,E groups with 15 in each g...Objective:To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rate.Methods:A total of 75 SD rate were randomly divided into A,B,C,D,E groups with 15 in each group.Rats in group A served as the control group received just only but tissue separation without modeling operation,while model of unilateral ureteral obstruction(UUO) was established in B,C,D,E groups.Rats in A,B group were given saline lavage placebo treatment,while rats in C,D,E groups were given dianunonium glycyrrhizinate and alprostadil injection.Five rats were sacrificed 1,2,3 weeks after modeling,serum creatinine level of femoral venous blood was determined.Transforming growth factor- β1(TCF- β1) and concentration of connective tissue growth factor(CTGF) were also detected by using ELISA.Line renal interstitial tissue was taken after HE staining,renal interstitial TGF- β1 and CTGF expression were detected by using immunohistochemical method.Results:Serum creatinine levels of B,C,D,E group at different time points in were significantly higher than that of group A(P<0.05);serum creatinine levels in group B were significantly higher than that of C,D,E group at each time point(P<0.05).Serum creatinine level of Croup E was significantly lower than C,D group after 2,3 weeks(P<0.05).Rate in A group at each time point showed no significant changes in TGF- β1 and CREA concentration in serum and kidney tissues(P>0.05);while serum and kidney tissue TGF- β1,concentration of CREA.expression of rats in B,C,D,E groups showed a gradual increasing trend over time.TCF- β1 and CREF of Group B in serum and kidney tissues at each time point were significantly higher than that of the other groups(P<0.05).TCF- β1 and CREF of Group E in serum and kidney tissues at each time point were significantly lower than that of B,C,D group at all time points in serum and kidney tissues(P<0.05).Conclusions:Alprostadil combined with diammonium glycyrrhizinate can significantly lower the expression of TGF- β1 and CTGF in serum and tissues of SD rat with renal interstitial fibrosis,thus inhibit rat renal interstitial fibrosis process.It has synergy protective effect.展开更多
AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was r...AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.展开更多
Compound glycyrrhizin tablets(CGT)is a glycyrrhizin-containing preparation for the treatment of chronic hepatic diseases,it contained Glycyrrhizin,Monoammonium Glycyrrhizinate,Aminoacetic Acid and Methionine.CGT has b...Compound glycyrrhizin tablets(CGT)is a glycyrrhizin-containing preparation for the treatment of chronic hepatic diseases,it contained Glycyrrhizin,Monoammonium Glycyrrhizinate,Aminoacetic Acid and Methionine.CGT has been shown to have anti-inflammatory,anti-oxidative,and anti-viral effects.Although pseudo-hyperaldosteronism was reported as its important side effects,the frequency was unknown.A 59-year-old male patient with tuberculous pleurisy received CGT to prevent impairment in liver function which was caused by antituberculosis drugs.After more than one month,it appeared edema in the lower extremity,blood pressure increased,serum potassium lowed,serum sodium raised at the normal high limit.Finally,it was improved by suspending the CGT and diuretic treatment.展开更多
Objective:To investigate influence of Compound Glycyrrhizin on liver functions, liver fibrosis indexes and inflammatory factors of patients with chronic hepatitis B.Methods:A total of 96 cases of patients with chronic...Objective:To investigate influence of Compound Glycyrrhizin on liver functions, liver fibrosis indexes and inflammatory factors of patients with chronic hepatitis B.Methods:A total of 96 cases of patients with chronic hepatitis B treated in our hospital from Jan2015 to Jun2016 were selected as subjects, and randomly divided to be 48 cases of observation group and 48 cases of control group. Patients in both of the two groups were received routine liver protecting drug treatment. For observation group, Compound Glycyrrhizin injection was given on the basis of routine treatment. Variations of liver function indexes, liver fibrosis indexes and inflammatory factors between the two groups before and after treatment were compared and observed.Results:No obvious difference showed on AST, ALT, ALB TBIL levels between two groups of patients before treatment;After treatment, AST, ALT, TBIL in two groups of patients were significantly decreased, ALB were significantly increased. Significant difference showed comparing with prior treatment;After treatment, AST, ALT and TBIL levels in observation group were (29.53±9.44) U/L, (32.36±10.93) U/L and (10.12±3.22) μmol/L, which were significantly lower than in control group. ALB levels in observation group were (43.57±12.42) g/L, which were significantly higher than ALB levels in control group. Before treatment, no statistical difference showed on HA, LN, IV-C and PCIII levels between two groups of patients. After treatment, HA, LN, IV-C and PCIII in two groups of patients were significantly decreased, which showed significant difference comparing with prior treatment;After treatment, HA, LN, IV-C and PCIII levels in observation group were (97.33±31.75) μg/L, (77.52±23.72) μg/L, (82.92±24.55) μg/L, (15.33±5.11) μg/L, which were significantly lower than in control group. Before treatment, no significant difference showed on IL-2, IL-6 and TNF- levels between two groups of patients;After treatment, IL-2 levels in two groups of patients were significantly increased, IL-6 and TNF-α were significantly decreased, the differences showed significance;After treatment, IL-2 levels in observation group were (131.48±30.63) U/mL, which were higher than IL-2 levels in control group. IL-6 and TNF-αlevels in observation group were (45.23±16.45) μg/L, (41.75±17.53) ng/L, which were lower than IL-6 and TNF-α levels in control group, differences showed significance.Conclusion:Compound Glycyrrhizin could effectively release liver fibrosis and inflammatory reactions for patients with chronic hepatitis B, and could further improve liver functions.展开更多
AIM:To examine how high-mobility group box 1 (HMGB1) regulates hepatocyte apoptosis and,furthermore,to determine whether glycyrrhizin (GL),a known HMGB1 inhibitor,prevents HMGB1-induced hepatocyte apoptosis.METHODS:A ...AIM:To examine how high-mobility group box 1 (HMGB1) regulates hepatocyte apoptosis and,furthermore,to determine whether glycyrrhizin (GL),a known HMGB1 inhibitor,prevents HMGB1-induced hepatocyte apoptosis.METHODS:A human hepatocellular carcinoma cell line stably transfected with a bile acid transporter (HuhBAT cells),were used in this study.Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride staining and the APO Percentage apoptosis assay,and its signaling cascades were explored by immunoblot analysis.Kinase signaling was evaluated by immunoblotting and by using selective inhibitors.It is also tried to identify hepatocyte apoptosis affected by the HMGB1 inhibitor,GL.RESULTS:HMGB1 increased cellular apoptosis in HuhBAT cells.HMGB1 led to increased cytochrome c release from mitochondria into the cytosol,and induced the cleavage of procaspase 3.However,it did not affect the activation of caspase 8.HMGB1-induced caspase 3 activation was significantly attenuated by the p38 inhibitor SB203580.GL significantly attenuated HMGB1-induced hepatocyte apoptosis.GL also prevented HMGB1-induced cytochrome c release and p38 activation in Huh-BAT cells.CONCLUSION:The present study demonstrated that HMGB1 promoted hepatocyte apoptosis through a p38dependent mitochondrial pathway.In addition,GL had an anti-apoptotic effect on HMGB1-treated hepatocytes.展开更多
Sea cucumbers, Apostichopus japonicus Selenka, were fed diets containing non-immunostimulant (basal diet), 0.2% β-glucan and 0.02% glycyrrhizin in a recirculatory water system for 45 days, and subsequently challenged...Sea cucumbers, Apostichopus japonicus Selenka, were fed diets containing non-immunostimulant (basal diet), 0.2% β-glucan and 0.02% glycyrrhizin in a recirculatory water system for 45 days, and subsequently challenged with Vibrio splendidus by injection at 1.0×108 cfu/sea cucumber for 15 days.Phagocytic capacity (PC), intracellular superoxide anion production (ISAP), ly-sozyme (LSZ) activity and superoxide dismutase (SOD) activity in the coelomic fluid were analyzed on the 0th, 5th, 10th and 15th days after injection.Results showed that after the 45-day feeding period, PC, ISAP, LSZ activity and SOD activity in sea cucumbers fed with dietary β-glucan or glycyrrhizin were significantly higher than in those fed with the basal diet.On the 5th day after infection, all the immune parameters examined in the sea cucumbers injected with V.splendidus decreased in value significantly.On the 15th day, PC, ISAP and LSZ activity returned to levels similar to those on the 0th day.For the sea cucumbers injected with saline, there were no significant differences in all the immune parameters examined and in the cumulative morbidity during the 15-day challenging trial.After injecting with V.splendidus, the cumulative morbidity of sea cucumbers fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin when challenged with V.splendidus challenged sea cucumber fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin.There was no significant difference in cumulative morbidity between the dietary β-glucan and glycyrrhizin treatments over time.展开更多
AIM: To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified byglycyrrhizin (BSA-NP-GL) and to develop a novel hepatoc...AIM: To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified byglycyrrhizin (BSA-NP-GL) and to develop a novel hepatocyte targeting BSA-NP-GL based on active targeting technology mediated by specific binding site of GL on rat cellular membrane. METHODS: Calcein loaded bovine serum albumin nanoparticles (Cal-BSA-NP) were prepared by desolvation process. Glycyrrhizin was conjugated to the surface reactive amino groups (SRAG) of Cal-BSA-NP by sodium periodate oxidization, which resulted in calcein-loaded bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (Cal-BSA-NP-GL). The morphology of the two types of prepared nanoparticles (NP) was observed by transmission electron microscopy. The diameter of NP was measured with a laser particle size analyzer. The interaction between Cal-BSA-NP-GL and primary cultured hepatocytes was studied through cellular uptake experiments. The uptake amount of Cal-BSA-NPGL and Cal-BSA-NP by rat hepatocytes was determinedby fluorospectrophotometry. Uptake characteristics were investigated through experiments of competitive inhibition of specific binding site of GL. RESULTS: Both Cal-BSA-NP-GL and Cal-BSA-NP had regular spherical surfaces. The average diameter of CalBSA-NP-GL and Cal-BSA-NP was 77 and 79 nm respectively. The uptake amount of the two NP by hepatocytes reached its maximum at 2 h after incubation. The uptake amount of Cal-BSA-NP-GL by rat hepatocytes was 4.43-fold higher than that of Cal-BSA-NP. There was a significant difference in the uptake of Cal-BSA-NP-GL and Cal-BSA-NP by hepatocytes (P＜0.01). The uptake of Cal-BSA-NP-GL was inhibited when GL was added previously to isolated rat hepatocytes, and the uptake of Cal-BSA-NP was not affected by GL.CONCLUSION: A binding site of GL is present on the surface of rat hepatocytes, BSA-NP-GL may be internalized via this site by hepatocytes and can be used as a drug carrier for active targeting of delivery drugs to hepatocytes.展开更多
Objective To evaluate the neuroprotective effects of glycyrrhizin(GL) on vascular dementia(VaD) in vivo and Glutamate-induced damage in vitro.Methods Male Wistar rats were subjected to permanent occlusion of the bilat...Objective To evaluate the neuroprotective effects of glycyrrhizin(GL) on vascular dementia(VaD) in vivo and Glutamate-induced damage in vitro.Methods Male Wistar rats were subjected to permanent occlusion of the bilateral common carotid arteries.On d 15 postsurgery,rat cognition was assessed using the Morris water maze.The activity of superoxide dismutase and the content of malondialdehyde of brains were also measured.Brain damage was evaluated histologically using HE staining.In vitro cell viability was examined in PC12 cells exposed to Glutamate,and mRNA levels of Bcl-2 and Bax were assessed.Results GL(20 mg/kg for 12 d) improved the performance of learning and memory of VaD rats,decreased the level of lipid peroxidation,and attenuated the pathological alterations in the hippocampal CA1 and CA3 areas.Moreover,GL(0.6 mmol/L) could protect PC12 cell lines from injury induced by Glutamate(10 mmol/L) and inhibit apoptosis of neuronal cells.Conclusion The present findings suggest that GL may have therapeutic potential in treating VaD.展开更多
Glycyrrhizin(GL)and Glycyrrhetic Acid 3-O-mono-β-D-glucuronide(GAMG)are the typical triterpenoid glycosides found in the root of licorice,a popular medicinal plant that exhibits diverse physiological effects and phar...Glycyrrhizin(GL)and Glycyrrhetic Acid 3-O-mono-β-D-glucuronide(GAMG)are the typical triterpenoid glycosides found in the root of licorice,a popular medicinal plant that exhibits diverse physiological effects and pharmacological manifestations.However,only few reports are available on the glycosylation enzymes involved in the biosynthesis of these valuable compounds with low conversion yield so far.In mammals,glycosyltransferases are involved in the phase II metabolism and may provide new solutions for us to engineer microbial strains to produce high valued compounds due to the substrate promiscuity of these glycosyltransferases.In this study,we mined the genomic databases of mammals and evaluated 22 candidate genes of O-glycosyltransferases by analyzing their catalytic potential for O-glycosylation of the native substrate,glycyrrhetinic acid(GA)for its glycodiversification.Out of 22 selected glycosyltransferases,only UGT1A1 exhibited high catalytic performance for biosynthesis of the key licorice compounds GL and GAMG.Molecular docking results proposed that the enzymatic activity of UGT1A1 was likely owing to the stable hydrogen bonding interactions and favorite conformations between the amino acid residues around substrate channels(P82~R85)and substrates.Furthermore,the complete biosynthesis pathway of GL was reconstructed in Saccharomyces cerevisiae for the first time,resulting in the production of 5.98±0.47 mg/L and 2.31±0.21 mg/L of GL and GAMG,respectively.展开更多
基金Supported by the Bourse du Conseil Médical de l’hôpital Erasme,Fonds E.et S.Jacobs and Novartis GrantThe CMMI is supported by the European Regional Development Fund and Wallonia
文摘BACKGROUND Acetaminophen overdose is the most frequent cause of drug-induced liver failure in developed countries.Substantial progress has been made in understanding the mechanism of hepatocellular injury,but N-acetylcysteine remains the only effective treatment despite its short therapeutic window.Thus,other hepatoprotective drugs are needed for the delayed treatment of acetaminopheninduced hepatotoxicity.Our interest focused on glycyrrhizin for its role as an inhibitor of high mobility group box 1(HMGB1)protein,a member of the family of damage-associated molecular pattern,known to play an important pathological role in various diseases.AIM To investigate the efficacy of the N-acetylcysteine/glycyrrhizin combination compared to N-acetylcysteine alone in the prevention of liver toxicity.METHODS Eight-week-old C57BL/6J wild-type female mice were used for all our experiments.Mice fasted for 15 h were treated with acetaminophen(500 mg/kg)or vehicle(phosphate-buffered saline)by intraperitoneal injection and separated into the following groups:Glycyrrhizin(200 mg/kg);N-acetylcysteine(150 mg/kg);and N-acetylcysteine/glycyrrhizin.In all groups,mice were sacrificed 12 h following acetaminophen administration.The assessment of hepatotoxicity was performed by measuring plasma levels of alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase.Hepatotoxicity was also evaluated by histological examination of hematoxylin and eosin-stained tissues sections.Survival rates were compared between various groups using Kaplan-Meier curves.RESULTS Consistent with data published in the literature,we confirmed that intraperitoneal administration of acetaminophen(500 mg/kg)in mice induced severe liver injury as evidenced by increases in alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase but also by liver necrosis score.Glycyrrhizin administration was shown to reduce the release of HMGB1 and significantly decreased the severity of liver injury.Thus,the co-administration of glycyrrhizin and N-acetylcysteine was investigated.Administered concomitantly with acetaminophen,the combination significantly reduced the severity of liver injury.Delayed administration of the combination of drugs,2 h or 6 h after acetaminophen,also induced a significant decrease in hepatocyte necrosis compared to mice treated with N-acetylcysteine alone.In addition,administration of N-acetylcysteine/glycyrrhizin combination was associated with an improved survival rate compared to mice treated with only N-acetylcysteine.CONCLUSION We demonstrate that,compared to N-acetylcysteine alone,co-administration of glycyrrhizin decreases the liver necrosis score and improves survival in a murine model of acetaminophen-induced liver injury.Our study opens a potential new therapeutic pathway in the prevention of acetaminophen hepatotoxicity.
文摘AIM:To examine the efficacy of glycyrrhizin preparation(GL-p) in the treatment of a rat model of ulcerative colitis(UC).METHODS:Experimental colitis was induced by oral administration of dextran sodium sulfate.Rats with colitis were intrarectally administered GL-p or saline.The extent of colitis was evaluated based on body weight gain,colon wet weight,and macroscopic damage score.The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis.The effect of GL-p on myeloperoxidase(MPO) activity in the inflamed mucosa and purified enzyme was assayed.RESULTS:GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline.Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines,including interleukin(IL)-1β,IL-6,tumor necrosis factor-α,cytokine-induced neutrophil chemoattractant-2,and monocyte chemoattractant protein-1 in the inflamed mucosa.Furthermore,GL-p inhibited the oxidative activity of mucosal and purified MPO.CONCLUSION:GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.
基金supported by Yantai Science and Technology Development Projects(2008142-19)
文摘Objective:To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rate.Methods:A total of 75 SD rate were randomly divided into A,B,C,D,E groups with 15 in each group.Rats in group A served as the control group received just only but tissue separation without modeling operation,while model of unilateral ureteral obstruction(UUO) was established in B,C,D,E groups.Rats in A,B group were given saline lavage placebo treatment,while rats in C,D,E groups were given dianunonium glycyrrhizinate and alprostadil injection.Five rats were sacrificed 1,2,3 weeks after modeling,serum creatinine level of femoral venous blood was determined.Transforming growth factor- β1(TCF- β1) and concentration of connective tissue growth factor(CTGF) were also detected by using ELISA.Line renal interstitial tissue was taken after HE staining,renal interstitial TGF- β1 and CTGF expression were detected by using immunohistochemical method.Results:Serum creatinine levels of B,C,D,E group at different time points in were significantly higher than that of group A(P<0.05);serum creatinine levels in group B were significantly higher than that of C,D,E group at each time point(P<0.05).Serum creatinine level of Croup E was significantly lower than C,D group after 2,3 weeks(P<0.05).Rate in A group at each time point showed no significant changes in TGF- β1 and CREA concentration in serum and kidney tissues(P>0.05);while serum and kidney tissue TGF- β1,concentration of CREA.expression of rats in B,C,D,E groups showed a gradual increasing trend over time.TCF- β1 and CREF of Group B in serum and kidney tissues at each time point were significantly higher than that of the other groups(P<0.05).TCF- β1 and CREF of Group E in serum and kidney tissues at each time point were significantly lower than that of B,C,D group at all time points in serum and kidney tissues(P<0.05).Conclusions:Alprostadil combined with diammonium glycyrrhizinate can significantly lower the expression of TGF- β1 and CTGF in serum and tissues of SD rat with renal interstitial fibrosis,thus inhibit rat renal interstitial fibrosis process.It has synergy protective effect.
基金Supported by The National Natural Science Foundation of China,No.30873464the Research Foundation from Ministry of Education of China,No.108019the Natural Science Foundation of Beijing,China,No.7132150
文摘AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.
文摘Compound glycyrrhizin tablets(CGT)is a glycyrrhizin-containing preparation for the treatment of chronic hepatic diseases,it contained Glycyrrhizin,Monoammonium Glycyrrhizinate,Aminoacetic Acid and Methionine.CGT has been shown to have anti-inflammatory,anti-oxidative,and anti-viral effects.Although pseudo-hyperaldosteronism was reported as its important side effects,the frequency was unknown.A 59-year-old male patient with tuberculous pleurisy received CGT to prevent impairment in liver function which was caused by antituberculosis drugs.After more than one month,it appeared edema in the lower extremity,blood pressure increased,serum potassium lowed,serum sodium raised at the normal high limit.Finally,it was improved by suspending the CGT and diuretic treatment.
文摘Objective:To investigate influence of Compound Glycyrrhizin on liver functions, liver fibrosis indexes and inflammatory factors of patients with chronic hepatitis B.Methods:A total of 96 cases of patients with chronic hepatitis B treated in our hospital from Jan2015 to Jun2016 were selected as subjects, and randomly divided to be 48 cases of observation group and 48 cases of control group. Patients in both of the two groups were received routine liver protecting drug treatment. For observation group, Compound Glycyrrhizin injection was given on the basis of routine treatment. Variations of liver function indexes, liver fibrosis indexes and inflammatory factors between the two groups before and after treatment were compared and observed.Results:No obvious difference showed on AST, ALT, ALB TBIL levels between two groups of patients before treatment;After treatment, AST, ALT, TBIL in two groups of patients were significantly decreased, ALB were significantly increased. Significant difference showed comparing with prior treatment;After treatment, AST, ALT and TBIL levels in observation group were (29.53±9.44) U/L, (32.36±10.93) U/L and (10.12±3.22) μmol/L, which were significantly lower than in control group. ALB levels in observation group were (43.57±12.42) g/L, which were significantly higher than ALB levels in control group. Before treatment, no statistical difference showed on HA, LN, IV-C and PCIII levels between two groups of patients. After treatment, HA, LN, IV-C and PCIII in two groups of patients were significantly decreased, which showed significant difference comparing with prior treatment;After treatment, HA, LN, IV-C and PCIII levels in observation group were (97.33±31.75) μg/L, (77.52±23.72) μg/L, (82.92±24.55) μg/L, (15.33±5.11) μg/L, which were significantly lower than in control group. Before treatment, no significant difference showed on IL-2, IL-6 and TNF- levels between two groups of patients;After treatment, IL-2 levels in two groups of patients were significantly increased, IL-6 and TNF-α were significantly decreased, the differences showed significance;After treatment, IL-2 levels in observation group were (131.48±30.63) U/mL, which were higher than IL-2 levels in control group. IL-6 and TNF-αlevels in observation group were (45.23±16.45) μg/L, (41.75±17.53) ng/L, which were lower than IL-6 and TNF-α levels in control group, differences showed significance.Conclusion:Compound Glycyrrhizin could effectively release liver fibrosis and inflammatory reactions for patients with chronic hepatitis B, and could further improve liver functions.
基金Supported by Samsung Biomedical Research Institute grant,No.SBRI C-A8-219-1
文摘AIM:To examine how high-mobility group box 1 (HMGB1) regulates hepatocyte apoptosis and,furthermore,to determine whether glycyrrhizin (GL),a known HMGB1 inhibitor,prevents HMGB1-induced hepatocyte apoptosis.METHODS:A human hepatocellular carcinoma cell line stably transfected with a bile acid transporter (HuhBAT cells),were used in this study.Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride staining and the APO Percentage apoptosis assay,and its signaling cascades were explored by immunoblot analysis.Kinase signaling was evaluated by immunoblotting and by using selective inhibitors.It is also tried to identify hepatocyte apoptosis affected by the HMGB1 inhibitor,GL.RESULTS:HMGB1 increased cellular apoptosis in HuhBAT cells.HMGB1 led to increased cytochrome c release from mitochondria into the cytosol,and induced the cleavage of procaspase 3.However,it did not affect the activation of caspase 8.HMGB1-induced caspase 3 activation was significantly attenuated by the p38 inhibitor SB203580.GL significantly attenuated HMGB1-induced hepatocyte apoptosis.GL also prevented HMGB1-induced cytochrome c release and p38 activation in Huh-BAT cells.CONCLUSION:The present study demonstrated that HMGB1 promoted hepatocyte apoptosis through a p38dependent mitochondrial pathway.In addition,GL had an anti-apoptotic effect on HMGB1-treated hepatocytes.
基金supported by grant No.2006AA100313 from the National High Technology Research and Development Project of P.R. China (863 Project)
文摘Sea cucumbers, Apostichopus japonicus Selenka, were fed diets containing non-immunostimulant (basal diet), 0.2% β-glucan and 0.02% glycyrrhizin in a recirculatory water system for 45 days, and subsequently challenged with Vibrio splendidus by injection at 1.0×108 cfu/sea cucumber for 15 days.Phagocytic capacity (PC), intracellular superoxide anion production (ISAP), ly-sozyme (LSZ) activity and superoxide dismutase (SOD) activity in the coelomic fluid were analyzed on the 0th, 5th, 10th and 15th days after injection.Results showed that after the 45-day feeding period, PC, ISAP, LSZ activity and SOD activity in sea cucumbers fed with dietary β-glucan or glycyrrhizin were significantly higher than in those fed with the basal diet.On the 5th day after infection, all the immune parameters examined in the sea cucumbers injected with V.splendidus decreased in value significantly.On the 15th day, PC, ISAP and LSZ activity returned to levels similar to those on the 0th day.For the sea cucumbers injected with saline, there were no significant differences in all the immune parameters examined and in the cumulative morbidity during the 15-day challenging trial.After injecting with V.splendidus, the cumulative morbidity of sea cucumbers fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin when challenged with V.splendidus challenged sea cucumber fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin.There was no significant difference in cumulative morbidity between the dietary β-glucan and glycyrrhizin treatments over time.
基金Supported by the National Natural Science Foundation of China,No. 30271613
文摘AIM: To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified byglycyrrhizin (BSA-NP-GL) and to develop a novel hepatocyte targeting BSA-NP-GL based on active targeting technology mediated by specific binding site of GL on rat cellular membrane. METHODS: Calcein loaded bovine serum albumin nanoparticles (Cal-BSA-NP) were prepared by desolvation process. Glycyrrhizin was conjugated to the surface reactive amino groups (SRAG) of Cal-BSA-NP by sodium periodate oxidization, which resulted in calcein-loaded bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (Cal-BSA-NP-GL). The morphology of the two types of prepared nanoparticles (NP) was observed by transmission electron microscopy. The diameter of NP was measured with a laser particle size analyzer. The interaction between Cal-BSA-NP-GL and primary cultured hepatocytes was studied through cellular uptake experiments. The uptake amount of Cal-BSA-NPGL and Cal-BSA-NP by rat hepatocytes was determinedby fluorospectrophotometry. Uptake characteristics were investigated through experiments of competitive inhibition of specific binding site of GL. RESULTS: Both Cal-BSA-NP-GL and Cal-BSA-NP had regular spherical surfaces. The average diameter of CalBSA-NP-GL and Cal-BSA-NP was 77 and 79 nm respectively. The uptake amount of the two NP by hepatocytes reached its maximum at 2 h after incubation. The uptake amount of Cal-BSA-NP-GL by rat hepatocytes was 4.43-fold higher than that of Cal-BSA-NP. There was a significant difference in the uptake of Cal-BSA-NP-GL and Cal-BSA-NP by hepatocytes (P＜0.01). The uptake of Cal-BSA-NP-GL was inhibited when GL was added previously to isolated rat hepatocytes, and the uptake of Cal-BSA-NP was not affected by GL.CONCLUSION: A binding site of GL is present on the surface of rat hepatocytes, BSA-NP-GL may be internalized via this site by hepatocytes and can be used as a drug carrier for active targeting of delivery drugs to hepatocytes.
文摘Objective To evaluate the neuroprotective effects of glycyrrhizin(GL) on vascular dementia(VaD) in vivo and Glutamate-induced damage in vitro.Methods Male Wistar rats were subjected to permanent occlusion of the bilateral common carotid arteries.On d 15 postsurgery,rat cognition was assessed using the Morris water maze.The activity of superoxide dismutase and the content of malondialdehyde of brains were also measured.Brain damage was evaluated histologically using HE staining.In vitro cell viability was examined in PC12 cells exposed to Glutamate,and mRNA levels of Bcl-2 and Bax were assessed.Results GL(20 mg/kg for 12 d) improved the performance of learning and memory of VaD rats,decreased the level of lipid peroxidation,and attenuated the pathological alterations in the hippocampal CA1 and CA3 areas.Moreover,GL(0.6 mmol/L) could protect PC12 cell lines from injury induced by Glutamate(10 mmol/L) and inhibit apoptosis of neuronal cells.Conclusion The present findings suggest that GL may have therapeutic potential in treating VaD.
基金supported by the National Key Research and Development Program of China(2018YFA0901800)the Key Research and Development Program of Hebei Province(21374301D)+2 种基金the Natural Science Foundation of China(No.22078171)the Natural Science Foundation of Hebei Province(No.C2019105055)the Scientific Research Foundation of Tangshan Normal University(No.2021B34).
文摘Glycyrrhizin(GL)and Glycyrrhetic Acid 3-O-mono-β-D-glucuronide(GAMG)are the typical triterpenoid glycosides found in the root of licorice,a popular medicinal plant that exhibits diverse physiological effects and pharmacological manifestations.However,only few reports are available on the glycosylation enzymes involved in the biosynthesis of these valuable compounds with low conversion yield so far.In mammals,glycosyltransferases are involved in the phase II metabolism and may provide new solutions for us to engineer microbial strains to produce high valued compounds due to the substrate promiscuity of these glycosyltransferases.In this study,we mined the genomic databases of mammals and evaluated 22 candidate genes of O-glycosyltransferases by analyzing their catalytic potential for O-glycosylation of the native substrate,glycyrrhetinic acid(GA)for its glycodiversification.Out of 22 selected glycosyltransferases,only UGT1A1 exhibited high catalytic performance for biosynthesis of the key licorice compounds GL and GAMG.Molecular docking results proposed that the enzymatic activity of UGT1A1 was likely owing to the stable hydrogen bonding interactions and favorite conformations between the amino acid residues around substrate channels(P82~R85)and substrates.Furthermore,the complete biosynthesis pathway of GL was reconstructed in Saccharomyces cerevisiae for the first time,resulting in the production of 5.98±0.47 mg/L and 2.31±0.21 mg/L of GL and GAMG,respectively.
