AIM: To investigate the protective effect of magnesium isoglycyrrhizinate(Mg IG) on excessive hepatectomy animal model and its possible mechanism.METHODS: We used the standard 90% hepatectomy model in Sprague-Dawley r...AIM: To investigate the protective effect of magnesium isoglycyrrhizinate(Mg IG) on excessive hepatectomy animal model and its possible mechanism.METHODS: We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond's method,in which the left,middle,right upper,and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups,and were injected intraperitoneally with 3 m L saline(control group),30 mg/kg(low-dose group) and 60 mg/kg(high-dose group) of Mg IG,respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamyl endopeptidase,total bilirubin(TBil),direct bilirubin(DBil),total protein,albumin,blood glucose(Glu),hyper-sensitivity C-reactive protein,prothrombin time(PT),and thrombin time(TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines(IL-1,IL-6,IL-10,and i NOS) was analyzed by ELISA. STAT3 protein and m RNA were analyzed by Western blot and quantitative reversetranscription PCR,respectively.RESULTS: The high-dose group demonstrated a significantly prolonged survival time,compared with both the control and the low-dose groups(22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h,P = 0.018). There were significant differences among the groups in ALT,Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the Mg IG treated groups than in the control group. Both Glu and PT levels were significantly higher in the Mg IG treated groups than in the control group. At 12 h,ALT,AST,TBil,DBil and TT levels showed significant differences between the Mg IG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group,the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10,and a decrease in IL-6. Both STAT3 protein and m RNA levels were significantly lower in the Mg IG treated groups than in the control group at 6 h,12 h,and 18 h after surgery.CONCLUSION: High-dose Mg IG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflam-matory response through inhibition of the STAT3 pathway.展开更多
Objective： Ethanol treatment induces an increase in oxidative stress. As licorice compounds are potent antioxidants, our aim was to examine whether magnesium isoglycyrrhizinate attenuated lipid peroxidation, the majo...Objective： Ethanol treatment induces an increase in oxidative stress. As licorice compounds are potent antioxidants, our aim was to examine whether magnesium isoglycyrrhizinate attenuated lipid peroxidation, the major end-point of oxidative damage resulting from ethanol administration. Methods： Four groups（18 animals in each group） of male Kunming mice were used. The first group served as control and received 0.4 ml normal saline daily for 18 days orally. The second group of mice was given 56% ethanol at 16 ml/kg body weight per day for 18 days orally. The third group was given the same dose of ethanol and administrated magnesium isoglycyrrhizinate （15 mg/kg.d, i.p.） for 18 days. The fourth group was given the same dose of ethanol and administrated with magnesium isoglycyrrhizinate （45 mg/kg.d, i.p.） for 18 days. Twenty four hours after 9 days or 18 days of treatment the mice were sacrificed using 10% chloral hydrate. Sperm counts and motility in the epididymis were assessed. The lipid peroxidation and antioxidants of testicular mitochondria were also determined. The pathological changes of testicle tissue of the mice were observed by light microscopy. Results： Magnesium isoglycyrrhizinate effectively prevented the ethanol-induced seminiferous epithelium disorganization and degeneration of Sertoli cells and germ cells. Sperm counts and motility of the magnesium isoglycyrrhizinate treated groups were higher than those of the alcohol treated group, but were lower than those of the control group. The drug exhibited an ability to counteract ethanol induced oxidative challenge as it effectively reduced testicular malondialdehyde （MDA） and increased the activities of superoxide dismutase and glutathione peroxidase. Conclusion： Magnesium isoglycyrrhizinate is able to inhibit the ethanol-induced lipid peroxidation and has a protective effect against testicular oxidative injury.展开更多
Objective Chemotherapy may cause drug-induced liver damage and studying the effectiveness of hepatoprotective substances in the clinical context is still warranted. We assessed the effectiveness of three commonly use...Objective Chemotherapy may cause drug-induced liver damage and studying the effectiveness of hepatoprotective substances in the clinical context is still warranted. We assessed the effectiveness of three commonly used natural substances for liver protection in East Asia. Methods： Retrospectively, we collected all medical records during a period of three years of cancer patients that underwent chemotherapy treatment and received glutathione, magnesium isoglicyrrhyzinate or polyene phosphatidylcholine at a Chinese integrative medicine hospital. Liver enzymes before and after one treatment cycle were detected. Paired t-test, chi-square, Snedcor＇s F distribution and ANOVA were used to analyze data. Results： 98 individuals were eligible for inclusion. After treatment, in the glutathione group, there were lower values in alanine aminotransferase （P 〈 0.05） and aspartate aminotransferase （P 〈 0.05）. There was also a lower level of liver injury in patients （P 〈 0.05）. In the magnesium isoglycyrrhizinate group there were lower values in total protein （P 〈 0.05）, alkaline phosphatase （P 〈 0.05） and gamma glutamyl transpeptidase values （P 〈 0.05）. There was also a lower level of liver injury in patients after treatment （P 〈 0.05）. In the polyene phosphatidylcholine group, there were no lower values of interest, including those of liver injury in patients （P 〉 0.05）. Conclusion： Glutathione and magnesium isoglicyrrhyzinate may be similarly effective in preserving liver function and preventing drug-induced liver injury in cancer patients undergoing chemotherapy. Polyene phosphatidylcholine may have no significant activity in protecting liver function and preventing drug-induced liver injury in advanced cancer patients undergoing chemotherapy. Since elevated glutathione levels may increase the antioxidant capacity and the resistance to oxidative stress by cancer cells, it is plausible to conclude that maintenance of high intracellular levels of glutathione could be critical for metastatic cells growth.展开更多
Objective To study the pharmacokinetics of intravenous magnesium isoglycyrrhizinate injection in health volunteers with HPLC-UV. Methods Single doses of 2OOmg magnesium isoglycyrrhizinate were administrated to 10 heal...Objective To study the pharmacokinetics of intravenous magnesium isoglycyrrhizinate injection in health volunteers with HPLC-UV. Methods Single doses of 2OOmg magnesium isoglycyrrhizinate were administrated to 10 health volunteers by i. v. infusion. The concentrations of magnesium isoglycyrrhizinate in plasma were assayed by HPLC-UV method. The pharmacokinetic parameters of magnesium isoglycyrrhizinate injection were calculated by program 3P87. Results The main pharmacokinetic parameters of intravenous magnesium isoglycyrrhizinate were as follows： cmax （ 67. 58 ± 8. 84 ） mg/L, T1/2α （ 1.46 ± 0. 35 ） h, T1/2β （ 23. 95 ± 4. 72 ） h, Vd （ 2. 921 ± 0. 382） L, CL （0. 186 ±0. 048） L/h,k10（0. 064 ±0. 016） h^-1, AUC0-T（1015.29 ±225. 14） mg·h^-1·L^-1 ,respectively. Conclusion We have successfully used the analytical method for magnesium isoglycyrrhizinate to study its pharmacokinetical properties of health volunteers after i. v. infusion. The method is found to be simple, accurate, stable and sensitive for application in clinical pharmacokinetics study. The concentration-time plot was fitted to a two-compartment open model with first-order elimination.展开更多
Background and Aims:Oxaliplatin is widely used in can-cer chemotherapy with adverse effects such as liver toxicity.Magnesium isoglycyrrhizinate(MgIG)has hepatoprotective effects,but the underlying mechanism remains el...Background and Aims:Oxaliplatin is widely used in can-cer chemotherapy with adverse effects such as liver toxicity.Magnesium isoglycyrrhizinate(MgIG)has hepatoprotective effects,but the underlying mechanism remains elusive.The study’s aim was to investigate the mechanism underlying the hepatoprotective effects of MgIG against oxaliplatin-induced liver injury.Methods:A xenografted colorectal cancer mouse model was established with MC38 cells.Mice were given ox-aliplatin(6 mg/kg/week)for 5 weeks to mimic oxaliplatin-induced liver injury in vivo.LX-2 human hepatic stellate cell s(HSCs)were employed for in vitro studies.Serological tests,hematoxylin and eosin staining,oil red O staining and trans-mission electron microscopy were used for histopathological examinations.Real-time PCR,western blotting,immuno-fluorescence and immunohistochemical staining were used to determine Cx43 mRNA or protein levels.Flow cytometry was used to assay reactive oxygen species(ROS)and mito-chondrial membrane.Short hairpin RNA targeting Cx43 was lentivirally transduced in LX-2 cells.Ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine MgIG and metabolite concentration.Results:MgIG(40 mg/kg/day)treatment significantly reduced se-rum aspartate transaminase(AST)and alanine transami-nase(ALT)levels in the mouse model,and alleviated liver pathological changes,including necrosis,sinusoidal expan-sion,mitochondrial damage,and fibrosis.MgIG reduced the abnormal expression of Cx43 in the mitochondria and nuclei of HSCs.MgIG inhibited the activation of HSCs via reducing ROS generation,mitochondrial dysfunction,and N-cadherin transcription.MgIG’s inhibition of HSCs activation was abol-ished after knockdown of Cx43 in LX-2 cells.Conclusions:Cx43 mediated MgIG’s hepatoprotective effects against ox-aliplatin-induced toxicity.展开更多
基金Supported by a grant from the State Science and Technology MinistryNo.2012BAI06B01
文摘AIM: To investigate the protective effect of magnesium isoglycyrrhizinate(Mg IG) on excessive hepatectomy animal model and its possible mechanism.METHODS: We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond's method,in which the left,middle,right upper,and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups,and were injected intraperitoneally with 3 m L saline(control group),30 mg/kg(low-dose group) and 60 mg/kg(high-dose group) of Mg IG,respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamyl endopeptidase,total bilirubin(TBil),direct bilirubin(DBil),total protein,albumin,blood glucose(Glu),hyper-sensitivity C-reactive protein,prothrombin time(PT),and thrombin time(TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines(IL-1,IL-6,IL-10,and i NOS) was analyzed by ELISA. STAT3 protein and m RNA were analyzed by Western blot and quantitative reversetranscription PCR,respectively.RESULTS: The high-dose group demonstrated a significantly prolonged survival time,compared with both the control and the low-dose groups(22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h,P = 0.018). There were significant differences among the groups in ALT,Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the Mg IG treated groups than in the control group. Both Glu and PT levels were significantly higher in the Mg IG treated groups than in the control group. At 12 h,ALT,AST,TBil,DBil and TT levels showed significant differences between the Mg IG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group,the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10,and a decrease in IL-6. Both STAT3 protein and m RNA levels were significantly lower in the Mg IG treated groups than in the control group at 6 h,12 h,and 18 h after surgery.CONCLUSION: High-dose Mg IG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflam-matory response through inhibition of the STAT3 pathway.
文摘Objective： Ethanol treatment induces an increase in oxidative stress. As licorice compounds are potent antioxidants, our aim was to examine whether magnesium isoglycyrrhizinate attenuated lipid peroxidation, the major end-point of oxidative damage resulting from ethanol administration. Methods： Four groups（18 animals in each group） of male Kunming mice were used. The first group served as control and received 0.4 ml normal saline daily for 18 days orally. The second group of mice was given 56% ethanol at 16 ml/kg body weight per day for 18 days orally. The third group was given the same dose of ethanol and administrated magnesium isoglycyrrhizinate （15 mg/kg.d, i.p.） for 18 days. The fourth group was given the same dose of ethanol and administrated with magnesium isoglycyrrhizinate （45 mg/kg.d, i.p.） for 18 days. Twenty four hours after 9 days or 18 days of treatment the mice were sacrificed using 10% chloral hydrate. Sperm counts and motility in the epididymis were assessed. The lipid peroxidation and antioxidants of testicular mitochondria were also determined. The pathological changes of testicle tissue of the mice were observed by light microscopy. Results： Magnesium isoglycyrrhizinate effectively prevented the ethanol-induced seminiferous epithelium disorganization and degeneration of Sertoli cells and germ cells. Sperm counts and motility of the magnesium isoglycyrrhizinate treated groups were higher than those of the alcohol treated group, but were lower than those of the control group. The drug exhibited an ability to counteract ethanol induced oxidative challenge as it effectively reduced testicular malondialdehyde （MDA） and increased the activities of superoxide dismutase and glutathione peroxidase. Conclusion： Magnesium isoglycyrrhizinate is able to inhibit the ethanol-induced lipid peroxidation and has a protective effect against testicular oxidative injury.
文摘Objective Chemotherapy may cause drug-induced liver damage and studying the effectiveness of hepatoprotective substances in the clinical context is still warranted. We assessed the effectiveness of three commonly used natural substances for liver protection in East Asia. Methods： Retrospectively, we collected all medical records during a period of three years of cancer patients that underwent chemotherapy treatment and received glutathione, magnesium isoglicyrrhyzinate or polyene phosphatidylcholine at a Chinese integrative medicine hospital. Liver enzymes before and after one treatment cycle were detected. Paired t-test, chi-square, Snedcor＇s F distribution and ANOVA were used to analyze data. Results： 98 individuals were eligible for inclusion. After treatment, in the glutathione group, there were lower values in alanine aminotransferase （P 〈 0.05） and aspartate aminotransferase （P 〈 0.05）. There was also a lower level of liver injury in patients （P 〈 0.05）. In the magnesium isoglycyrrhizinate group there were lower values in total protein （P 〈 0.05）, alkaline phosphatase （P 〈 0.05） and gamma glutamyl transpeptidase values （P 〈 0.05）. There was also a lower level of liver injury in patients after treatment （P 〈 0.05）. In the polyene phosphatidylcholine group, there were no lower values of interest, including those of liver injury in patients （P 〉 0.05）. Conclusion： Glutathione and magnesium isoglicyrrhyzinate may be similarly effective in preserving liver function and preventing drug-induced liver injury in cancer patients undergoing chemotherapy. Polyene phosphatidylcholine may have no significant activity in protecting liver function and preventing drug-induced liver injury in advanced cancer patients undergoing chemotherapy. Since elevated glutathione levels may increase the antioxidant capacity and the resistance to oxidative stress by cancer cells, it is plausible to conclude that maintenance of high intracellular levels of glutathione could be critical for metastatic cells growth.
文摘Objective To study the pharmacokinetics of intravenous magnesium isoglycyrrhizinate injection in health volunteers with HPLC-UV. Methods Single doses of 2OOmg magnesium isoglycyrrhizinate were administrated to 10 health volunteers by i. v. infusion. The concentrations of magnesium isoglycyrrhizinate in plasma were assayed by HPLC-UV method. The pharmacokinetic parameters of magnesium isoglycyrrhizinate injection were calculated by program 3P87. Results The main pharmacokinetic parameters of intravenous magnesium isoglycyrrhizinate were as follows： cmax （ 67. 58 ± 8. 84 ） mg/L, T1/2α （ 1.46 ± 0. 35 ） h, T1/2β （ 23. 95 ± 4. 72 ） h, Vd （ 2. 921 ± 0. 382） L, CL （0. 186 ±0. 048） L/h,k10（0. 064 ±0. 016） h^-1, AUC0-T（1015.29 ±225. 14） mg·h^-1·L^-1 ,respectively. Conclusion We have successfully used the analytical method for magnesium isoglycyrrhizinate to study its pharmacokinetical properties of health volunteers after i. v. infusion. The method is found to be simple, accurate, stable and sensitive for application in clinical pharmacokinetics study. The concentration-time plot was fitted to a two-compartment open model with first-order elimination.
基金the Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica(No.JKLPSE201501)the Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine(No.2020YLXK20)the Science and Technology Development Foundation of Nanjing Medical University(No.NMUB2019186).
文摘Background and Aims:Oxaliplatin is widely used in can-cer chemotherapy with adverse effects such as liver toxicity.Magnesium isoglycyrrhizinate(MgIG)has hepatoprotective effects,but the underlying mechanism remains elusive.The study’s aim was to investigate the mechanism underlying the hepatoprotective effects of MgIG against oxaliplatin-induced liver injury.Methods:A xenografted colorectal cancer mouse model was established with MC38 cells.Mice were given ox-aliplatin(6 mg/kg/week)for 5 weeks to mimic oxaliplatin-induced liver injury in vivo.LX-2 human hepatic stellate cell s(HSCs)were employed for in vitro studies.Serological tests,hematoxylin and eosin staining,oil red O staining and trans-mission electron microscopy were used for histopathological examinations.Real-time PCR,western blotting,immuno-fluorescence and immunohistochemical staining were used to determine Cx43 mRNA or protein levels.Flow cytometry was used to assay reactive oxygen species(ROS)and mito-chondrial membrane.Short hairpin RNA targeting Cx43 was lentivirally transduced in LX-2 cells.Ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine MgIG and metabolite concentration.Results:MgIG(40 mg/kg/day)treatment significantly reduced se-rum aspartate transaminase(AST)and alanine transami-nase(ALT)levels in the mouse model,and alleviated liver pathological changes,including necrosis,sinusoidal expan-sion,mitochondrial damage,and fibrosis.MgIG reduced the abnormal expression of Cx43 in the mitochondria and nuclei of HSCs.MgIG inhibited the activation of HSCs via reducing ROS generation,mitochondrial dysfunction,and N-cadherin transcription.MgIG’s inhibition of HSCs activation was abol-ished after knockdown of Cx43 in LX-2 cells.Conclusions:Cx43 mediated MgIG’s hepatoprotective effects against ox-aliplatin-induced toxicity.
