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Objective: Tripterygium glycoside (TG) is widely used in clinical practice for its multiple bioactivities including anti-inflammatory and immunosuppressive effects. However, emerging studies have frequently reported TG-induced adverse reactions to multiple organs, especially liver. Here, this study aimed to investigate the mechanism of liver damage induced by TG and explore representative components to reflect TG hepatotoxicity. Methods: Network pharmacology was used to determine the potential targets of bile duct injury caused by TG. Next, the hepatotoxic effects of TG, triptolide (TP) and celastrol (CEL) were investigated and compared in vivo and in vitro. Liver function was determined by measuring serum transaminase and histopathology staining. The cell proliferation and apoptosis were determined by cell viability assay, scratch assay and flow cytometry. The expression of gene of interest was determined by qPCR and Western blot. Results: Based on the network pharmacological analysis of 12 bioactive ingredients found in TG, a total of 35 targets and 15 pathways related to bile duct injury were obtained. Both TG and TP resulted in cholangiocyte damage and liver injury, as illustrated by increased levels of serum transaminase and oxidative stress, stimulated portal edema and lymphocytic infiltration and decreased expression of cholangiocyte marker, cytoskeletal 19. In addition, TG and TP inhibited cell proliferation and migration, arrested cell cycle and promoted Caspase-dependent apoptosis of cholangiocytes via suppressing the phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) and protein kinase B (AKT). While, CEL at equivalent dosage had no obvious hepatotoxicity. Conclusion: We revealed that TG-stimulated liver injury was specifically characterized by cholangiocyte damage and TP might be the decisive ingredient to reflect TG hepatotoxicity. Our results not only provide novel insights into the mechanism underlying the hepatotoxicity effects of TG but also offer reference for clinical rational use of TG.
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Objective To investigate the effects of tripterygium glycosides on autophagy of renal cells in rats with diabetic nephropathy and to analyze its molecular mechanism. Methods A rat model of diabetic nephropathy was made by intraperitoneal injection of streptavidin. Thirty SD rats were randomly divided into 5 groups, control group, model group, 0. 1 mg/ kg drug group, 0. 5 mg/ kg drug group and 1. 0 mg/ kg drug group, and each group has 6 rat. After the successful establishment of the diabetic nephropathy model, the 0. 1 mg/ kg drug group, the 0. 5 mg/ kg drug group, and the 1. 0 mg/ kg drug group were intragastric administration with 0. 1, 0. 5, and 1. 0 mg/ kg tripterygium glycosides, respectively, and the control group and the model group were intraperitoneally injected with the same amount of normal saline. The levels of renal function and oxidative stress were compared among groups. The expression levels of p-mammalian target of rapamycin (p-mTOR), mammalian target of rapamycin(mTOR), microtubules associated protein 1 light chain 3β-Ⅱ/ microtubules associated protein 1 light chain 3β-Ⅰ (LC3-Ⅱ/ LC3-Ⅰ) and Beclin1 protein were detected by Western blotting. The expression levels of LC3, LC3-Ⅱ and Beclin1 mRNA in each group were detected by Real-time PCR. Results Compared with the control group, the serum creatinine (Scr), blood urea nitrogen (BUN), protein (Pro) and malondialdehyde (MDA) levels in the model group increased, and the the glutathione peroxidase (GSH-Px) and catalase (CAT) levels decreased significantly (P<0. 05) . Compared with the model group, the Scr, BUN, Pro and MDA levels of the drug group were significantly decreased, and GSH-Px and CAT levels were significantly increased in a dose-dependent manner (P < 0. 05) . Compared with the control group, the expression level of p-mTOR protein in the renal tissue of the model group was increased, and the expression levels of LC3-Ⅱ / LC3-Ⅰ and Beclin1 protein were decreased (P<0. 05) . Compared with the model group, the expression level of p-mTOR protein was decreased in the dose group, and the expression levels of LC3-Ⅱ / LC3-Ⅰ protein in the dose group were significantly increased in a dose-dependent manner (P<0. 05) . The expression levels of Beclin1 protein in the 0. 5 mg / kg drug group and 1. 0 mg / kg drug group, were significantly higher than the model group (P<0. 05) . Compared with the control group, the expression levels of LC3-Ⅱ / LC3-Ⅰ and Beclin1 mRNA in the renal tissue of the model group were significantly lower (P<0. 05) . Compared with the model group, the expression levels of LC3 and Beclin1 mRNA in the drug groups of each dose group were significantly increased (P < 0. 05) . Conclusion Tripterygium wilfordii glycosides can protect kidney function in rats with diabetic nephropathy, and its mechanism might be related to inhibition of oxidative stress and activation of autophagy.
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Objective To investigate the effect of tripterygium glycosides on the resistance to immune rejection after allogeneic islet transplantation in mice.Methods Twenty C57BL/6 mice were treated with STZ diabetes mellitus and transplanted the islets from Balb/c mice donor,then recipient mice were randomly divided into two groups:triptolide group and model control group(n=10),and were intraperitoneal injected with tripterygium glycoside solutin and equivalent solvent of 5 mg·kg-1·d-1 for 14 days.Blood glucose and body weight were measured within 4 weeks after transplantation.Two weeks later,two groups of grafted islets were stained by HE staining and immunohistochemical staining,the expression of IL-2 protein were detected by Western blotting.Results The level of blood glucose were decreased to normal in the triptolide group and model control group after islet transplantation,but blood glucose gradually increased in the model control group after two weeks.Compared with the model control group,the inflammatory cells were less infiltrated and the immunohistochemical staining of insulin was deeper in the triptolide group.The expression of IL-2 in the triptolide group was significantly decreased(P<0.05).Conclusion Tripterygium glucoside could significantly decrease the inflammatory cell infiltration and inflammation factor expression in the allogeneic islet recipients to reduce the immune rejection and improve graft survival.
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Objective To investigate the efficacy of Ginkgo‐Leaf Capsule combined with tripterygium glycoside in the treat‐ment of diabetic nephropathy(DN) and its influence on CysC ,Hcy and VEGF .Methods Eighty patients with DN treated in our hospital from January 2013 to April 2015 were selected as research subjects and equally divided into the control group and the ob‐servation group according to the random number table ,40 cases in each group .Besides the conventional Western medicine treat‐ment ,the control group was given tripterygium glycoside ,while the observation group was given Kinkgo‐Leaf Capsule combined with tripterygium glycoside .The treatment course was 3 months .Then ,the curative efficacy ,indices of renal function ,levels of Cy‐sC ,Hcy and vascular endothelial growth factor(VEGF) ,and occurrence situation of adverse reactions were compared between the two groups .Results The total therapeutic efficacy rate in the observation group and the control group was 92 .50% and 80 .00%respectively without statistically significant difference (P>0 .05) .In the comparison with the control group after treatment ,the re‐nal function indices of serum creatinine ,urea nitrogen ,24 h urinary protein ,level of serum CysC ,Hcy and VEGF in the observation group were statistically decreased (P0 .05) .Conclusion Ginkgo‐Leaf Capsule combined with tripterygium glycoside is effective and reliable for treating DN ,which can significantly improve the renal function ,reduces the level of serum CysC ,Hcy and VEGF .
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OBJECTIVE: To investigate the hepatoprotective effects of Lysimachia christinae Hance against acute liver injury induced by tripterygium glycosides (TG) in vivo and the related mechanism for the first time. METHODS: The mice were administered ethanol extract of L. christinae (JE), water extract of L. christinae (JW), and bifendate by ig for seven consecutive days. 12 h after the last dose, the mice were orally given TG 270 mg · kg-1 except those in the normal group. Serum and liver tissue samples were collected at 18 h after TG treatment. Besides, the amounts of quercetin and kaempferol in JE and JW were analyzed by high-performance liquid chromatography (HPLC). RESULTS: TG-induced elevated serum alanine transferase(ALT) and aspartate transaminase (AST) activities were significantly reduced by JE(100, 200 mg · kg-1) in dose-dependent manners, but not by JW. Further analysis demonstrated that lipid peroxidation(LPO) level significantly decreased, while superoxide dismutase(SOD) and catalase(CAT) activities increased in livers of JE-treated mice. Besides, the amounts of quercetin and kaempferol were 9.8 and 8.9 mg · g-1 in JE, and 2.8 and 1.9 mg · g-1 in JW, respectively. CONCLUSION: This study for the first time demonstrates that L. christinae can protect against TG-induced acute liver injury in dose-dependent manners in vivo, the potential mechanism may be related to inhibiting liver oxidative stress injury, and the hepatoprotective activity may be correlated with the contents of quercetin and kaempferol. Copyright 2013 by the Chinese Pharmaceutical Association.
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0.05). Conclusion:Certain concentration of TG can inhibit the apoptosis of Schwann’s cell and the expression of major histocompatibility antigen of cold preserved sciatic nerve in rats,and decrease rejection after nerve allograft.
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Objective To explore the effects of Baogan Jiedu Granule on lipid peroxidation of free radicals in acute liver injury mice induced by tripterygium glycosides.Methods Totally 60 mice were randomly divided into tripterygium glycosides model group,large-dose,medium-dose and small-dose groups of Baogan Jiedu Granule,Ganlixin group and control group.Each group was respectively perfused with the corresponding drug for 5 days and tripterygium glycosides were perfused once to make the model.The serum levels of ALT,AST,SOD,MDA and GSH-Px were measured.Results The serum levels of SOD and GSH-Px in model group decreased and MDA rose obviously.Compared with model group,Baogan Jiedu Granule of all doses could effectively decrease ALT,AST and MDA level and obviously improve GSH-Px level in each group.In addition,in the large-dose group SOD level was markedly improved(P