Effect of Tripterygium Glycosides Tablets in treating rheumatoid arthritis:a systematic review and Meta-analysis / 中国中药杂志

To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.

Identification of biomarkers to response of Tripterygium Glycosides Tablets acting on rheumatoid arthritis by integrating transcriptional data mining and biomolecular network analysis / 中国中药杂志

Growing clinical evidence shows that a partial rheumatoid arthritis( RA) patient treated with Tripterygium Glycosides Tablets( TGT) may fail to achieve clinical improvement. It is of great clinical significance to predict the therapeutic effect of TGT in RA. Therefore,the aim of the current study was to identify potential biomarkers for TGT treatment in RA. Affymetrix EG1.0 arrays were applied to detect gene expression in peripheral blood mononuclear cells obtained from 6 RA patients( 3 responders and 3 non-responders) treated with TGT. By integrating differential expression data analysis and biomolecular network analysis,360 mRNAs( 185 up-regulated and 175 down-regulated) and 24 miRNAs( 7 up-regulated and 17 down-regulated) which were differentially expressed between TGT responder and non-responder groups were identified. A total of 206 candidate target genes for the differentially expressed miRNAs were obtained based on miRanada and Target Scan databases,and then the miRNA target gene coexpression network and miRNA-mediated gene signal transduction network were constructed. Following the network analyses,three candidate miRNAs biomarkers( hsa-miR-4720-5 p,hsa-miR-374 b-5 p,hsa-miR-185-3 p) were identified as candidate biomarkers predicting individual response to TGT. Partialleast-squares( PLS) was applied to construct a model for predicting response to TGT based on the expression levels of the candidate gene biomarkers in RA patients. The five-fold cross-validation showed that the prediction accuracy( ACC) of this PLS-based model efficacy was 100.00%,100.00%,100.00%,66.67% and 66.67% respectively,and all the area under the receiver operating characteristic curve( AUC) were 1.00,indicating the highly predictive efficiency of this PLS-based model. In conclusion,the integrating transcription data mining and biomolecular network investigation show that hsa-mir-4720-5 p,hsa-mir-374 b-5 p and hsa-mir-185-3 p may be candidate biomarkers predicting individual response to TGT. In addition,the PLS model based on the expression levels of these candidate biomarkers may be helpful for the clinical screen of RA patients,which potentially benefit individualized therapy of RA in a daily clinical setting.

Effect of Tripterygium Glycosides Tablets on synovial angiogenesis in rats with type Ⅱ collagen induced arthritis / 中国中药杂志

To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 μg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.

Study on mechanism of Cuscutae Semen flavonoids in improving reproductive damage of Tripterygium Glycosides Tablets in rats based on high-throughput transcriptome sequencing / 中国中药杂志

Tripterygium Glycosides Tablets has good anti-inflammatory and immunomodulatory activities,but its reproductive damage is significant. Previous studies of the research group have found that Cuscutae Semen flavonoids can improve spermatogenic cell damage caused by Tripterygium Glycosides Tablets by regulating spermatogenic cell cycle,apoptosis and related protein expression,but the mechanism of action at the gene level is still unclear. In this study,Illumina high-throughput sequencing platform was applied in transcriptional sequencing of spermatogenic cells of rats after the intervention of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets. Differentially expressed genes were screened out and the GO enrichment and KEGG pathway analysis of differentially expressed genes were conducted to explore the mechanism of Cuscutae Semen flavonoids in improving reproductive injury caused by Tripterygium Glycosides Tablets. The results showed that 794 up-regulated genes and 491 down-regulated genes were screened in Tripterygium Glycosides Tablets group compared with the blank group. Compared with Tripterygium Glycosides Tablets,440 up-regulated genes and 784 down-regulated genes were screened in the Cuscutae Semen flavonoids+Tripterygium Glycosides Tablets group. Among them,the gene closely related to reproductive function is DNMT3 L. Analysis of GO function and KEGG signaling pathway enrichment showed that the above differentially expressed genes were mainly enriched in cell,cell process,catalytic activity,binding,ovarian steroid synthesis,thyroid hormone and other functions and pathways. The thyroid hormone signaling pathway was the common enrichment pathway of the two control groups. In a word,Cuscutae Semen flavonoids has a good treatment effect on male reproductive damage caused by Tripterygium Glycosides Tablets. The mechanism may be closely related to up-regulation of DNMT3 L genes and intervention of thyroid hormone signaling pathway. At the same time,the discovery of many different genes provides valuable information for study on the mechanism of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets compatibility decreasing toxicity and increasing efficiency.

Effect of Tripterygium Glycosides Tablets on reproductive toxicity in female rats with Ⅱ type collagen induced arthritis / 中国中药杂志

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets( TG) on the reproductive system of Ⅱ type collagen induced arthritis( CIA) male rats,and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group( Con),model group( CIA),Tripterygium Glycosides Tablets clinical equivalent dose groups of 1,2,4 times( 9,18,36 mg·kg-1),10 rats in each group,and were given by gavage once a day for 42 days after the first immunization.The organ indexes of uterine and ovarian were calculated on days 21 and 42. Histopathological and morphological changes of uterine and ovarian were observed under optical microscope. The concentration of estradiol( E2),follicle-stimulating hormone( FSH),luteinizing hormone( LH),17α-hydroxylase( CYP17 A1) and cytochrome P450 19 A1( CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of uterus and ovary. The results showed that compared with the Con group,CIA group could reduce the number of uterine glands( P<0.05),but no significant changes were observed in other groups. Compared with the CIA group,there were no significant changes in the coefficients of uterus and ovary in the Tripterygium Glycosides Tablets groups. The number of uterine glands,total follicles in the ovary,mature follicles and corpus luteum,the distribution of blood vessels and mitochondria had a certain inhibitory trend,and also slightly increased the number of atresia follicles,but the histopathological quantitative indicators were not statistically different. Except that 2 times clinical dose of Tripterygium Glycosides Tablets could significantly reduce the content of CYP19 A1( P<0. 05) after 42 d administration,there were no significant changes in serum estrogen E2,FSH,LH and estrogen synthesis key enzymes CYP17 A1 in each administration group. Medium and high doses of Tripterygium Glycosides Tablets could increase the expression of apoptotic protein Bax in uterine and ovarian tissues( P<0. 05,P<0. 01),and all the administration groups could inhibit the expression of apoptotic inhibiting protein Bcl-2( P <0. 05,P<0. 01,P<0.001),42 d was more obvious than 21 d. In conclusion,4 times and less than 4 times Tripterygium Glycosides Tablets did not cause obvious toxicity and histopathological changes in the reproductive organs of CIA rats,but it could reduce the level of serum estrogen synthesis key enzyme CYP19 A1 and affect the content of apoptosis-related proteins Bax and Bcl-2 in uterus and ovary tissues. The relevant mechanism needs further study.

Effects of Tripterygium Glycosides Tablets from 6 different manufacturers on acute liver injury of normal mice / 中国中药杂志

The aim of this paper was to compare the performance of acute liver injury in mice induced by Tripterygium Glycosides Tablets from 6 different manufacturers,and to explore the toxicity mechanism from the perspective of oxidative stress and apoptosis preliminarily. Male or female mice were randomly divided into normal group,Zhejiang group,Hunan group,Hubei group,Shanghai group,Jiangsu group and Fujian group. Mice in Tripgerygium Glycosides Tablets groups were given 16 times the clinical equivalent dose( 300 mg·kg-1) Tripgerygium Glycosides Tablets by oral administration for one time,mice were executed in 24 h after lavaged.Then the visceral brain coefficient of the organ was calculated. Histopathological changes of liver were observed by hematoxylin-eosin staining. Td T-mediated d UTP nick-end labeling was used to detect the apoptosis of the liver cells and the protein content of oxidative stress related factors in liver homogenate. Nuclear transcription factor E2-related factor( Nrf2) and heme oxygenase-1( HO-1) as well as mitochondrial mediated apoptosis-related protein expression levels of Bax and Bcl-2 in hepatic tissue were measured by Western blot.Within 24 hours of administration,6 male mice in Jiangsu group and 2 female mice in Zhejiang group were dying; compared with normal ones,liver coefficients of mice in Zhejiang,Shanghai,Jiangsu and Hunan groups were significantly increased,thymus coefficients in the first two groups were significantly reduced,as well as the lung coefficients of Fujian group mice,the rest was normal. In addition to Hubei group,serum AST,ALT or ALP levels of mice were increased,while TBi L were not being affected. Histopathological changes and apoptosis of liver cells were observed in all mice,and the degree of severity was ranked as Jiangsu,Zhejiang,Shanghai,Hunan,Hubei and Fujian group. All Tripterygium Glycosides Tablets increased the MDA and reduced the content of T-SOD,CAT or GSH in liver tissue while inhibited Nrf2,HO-1 and Bcl-2,increased the protein expression level of Bax( except Hunan group). Tripgerygium Glycosides Tablets from 6 manufacturers all resulted in liver function damage and liver histopathological changes,especially in Jiangsu,Hubei and Fujian,and the mechanism may related to inhibit Nrf2/HO-1 oxidative stress pathway and activate Bax/Bcl-2 apoptosis pathway to mediate lipid peroxidation and induce liver cell apoptosis. Triptolide A may be one of the main toxic components of Tripgerygium Glycosides Tablets that causing drug-induced liver injury. This study was conducted on normal mice with super dose medication,so the relevant results are for reference only.

Comparative study on dose-toxicity-effect of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets on CIA model rats / 中国中药杂志

The aim of this paper was to compare the properties of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets from dose-effect-toxicity on type Ⅱ collagen-induced arthritis( CIA) in rats. SD rats were randomly divided into eight groups,including normal group,model group,Tripterygium Glycosides Tablets groups( 1 times equivalent dose 0.009 g·kg-1,4 times equivalent dose 0.036 g·kg-1,16 times equivalent dose 0.144 g·kg-1),Tripterygium wilfordii Tablets groups( 1 times equivalent dose 0.007 5 mg·kg-1,4 times equivalent dose 0.030 mg·kg-1,16 times equivalent dose 0.120 mg·kg-1). Beginning on the first immunization,Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets administered intraperitoneally once a day. After the second immunization,the symptoms such as redness and swelling of joints were observed,and the clinical score and incidence of arthritis were evaluated. HE and Masson staining were used to examine the histopathological changes of joints. The expression level of anti-type Ⅱ collagen antibody Ig G in serum was detected by ELISA,routine testing of blood components,the concentration of ALP( alkaline phosphatase),ALT( alanine aminotransferase),AST( aspartate aminotransferase),GGT( gamma-glutamyltransferase),TBi L( total bilirubin),CRE( creatinine) and UREA( urea) in serum were detected by enzymatic assay. The rate of sperm deformity in the epididymis was evaluated under light microscope. The extent of damage to the testis and ovarian tissue was assessed by HE staining. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets attenuated the inflammation,redness,swelling and deformity of joints and reduced the clinical score and incidence of arthritis in CIA rats. Meanwhile,it also exhibited obvious reduction in all pathological features such as joint synovitis,pannus,cartilage erosion and bone destruction. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets reduced Ig G in a dose-dependent manner,and Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets( P<0.05 or P<0.01). The high doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase the organ coefficient of liver and spleen and reduced RBC and HGB in CIA rats( P<0.01),and severity leading to death. Gastric mucosal injury and morphological changes of liver and kidney were not observed in CIA rats of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets treatment group. The 4 and 16 times doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase serum ALT,GGT and decrease CRE( P<0.05 or P<0.01). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could increase the sperm deformity rate and damage the testicular seminiferous tubules of CIA male rats. Severity increased with dose and time increasing. The effect of Tripterygium Glycosides Tablets( 16 times) is more significant than Tripterygium wilfordii Tablets( 16 times). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets significantly delayed onset of arthritis and inhibited the paw edema and arthritic score. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets also caused male reproductive damage,high dose affected hematopoiesis,and maximum dose leading to death. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets all depended on dose-effect-toxicity manner. Anti-arthritis effect of Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets,but the toxicity of Tripterygium Glycosides Tablets maximum dose is more obvious. The relevant conclusions of our study will provide experimental references for clinical rational use of drugs,and further clinical studies are needed to confirm our conclusions.

Effect of Tripterygium Glycosides Tablets on immune-induced liver and kidney function in patients with rheumatoid arthritis based on data mining / 中国中药杂志

This paper aims to investigate the effect of oral administration of Tripterygium Glycosides Tablets combined with traditional Chinese medicine on immune inflammatory index in patients with rheumatoid arthritis,in order to explore the compatibility mode of traditional Chinese medicine in the treatment of rheumatoid arthritis. Medical records of hospitalized patients with rheumatology at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from June 2012 to December 2017 were collected. The combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine was adopted for the experimental group,while the simply administration of Tripterygium Glycosides Tablets were adopted for the control group. SPSS 21. 0 was used to analyze the changes of general conditions and immune inflammatory metabolic indexes in the two groups of RA patients. The association rules were analyzed by SPSS Clementine 14. 2 software Apriori module,and the random walk model was evaluated by ORACLE 10 g tool. The results showed that a total of 1 220 patients with rheumatoid arthritis met the requirements of this study,including 322 in the experimental group and 898 in the control group. Before treatment,there was no significant difference in age and duration between the two groups. The difference value of Ig A,Ig G,RF,CCP-AB,hs-CRP and ESR in the two groups of RA patients decreased before and after treatment,and the experimental group was superior to the control group in reduction of Ig A,Ig G,RF,CCP-AB,hs-CRP and ESR.The control group was superior to the experimental group in reduction of Ig M( P<0. 01 or P<0. 05). Compared with before treatment,ALT,AST,ALP,GGT,CREA,BUN,b-MG,MA,TRU and Ig U all increased,with statistically significant differences( P<0. 01).The UA of the two groups of RA patients decreased after treatment,with statistically significant differences( P<0. 01). The experimental group was superior to the control group in reduction of UA,with statistically significant differences( P < 0. 05 or P < 0. 01). The herbs adopted in the prescriptions of 1 220 patients were mainly classified into four categories,namely spleen-sweating herbs,blood-activating and stasis-relieving herbs,phlegm and phlegm-relieving herbs,and heat-clearing and antidote herbs. The results of association rule analysis indicated a significant correlation between the single-flavored Tripterygium Glycosides Tablets,oral Chinese medicine and immune inflammation,and improvement of liver and kidney function indexes. The results of the random walk model analysis indicated that the experimental group's Ig M and hs-CRP were superior to those of the control group in terms of random fluctuation maximum,walking positive growth rate,comprehensive evaluation index increasing rate,comprehensive improvement rate,comprehensive evaluation index recording times,and expected improvement value. The results of this study showed that the single administration of Tripterygium Glycosides Tablets can effectively improve the immune inflammatory metabolic index of patients with rheumatoid arthritis,and the combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine could alleviate the immune inflammatory index of RA patients and reduce liver and kidney dysfunction compared with simple oral administration. The comprehensive evaluation Ig M and hs-CRP in the group of combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine were better than those in the group of the Tripterygium Glycosides Tablets. There was a long-term correlation between the comprehensive evaluation index and the intervention measures of the two groups of patients.

Clinical symptoms effect of Tripterygium Glycosides Tablets alone or combined with methotrexate in treatment of rheumatoid arthritis: a Meta-analysis / 中国中药杂志

To systematically review the improvement effects of Tripterygium Glycosides Tables( TGT) alone or in combination with methotrexate( MTX) on the clinical signs and symptoms of rheumatoid arthritis( RA),and provide a basis for the rational use of TGT in clinic,in the current study,six literature databases including CNKI,Wan Fang,VIP,PubMed,EMbase,and Cochrane Library,were systematically searched,according to the inclusion and exclusion criteria. Review Manager 5.3 software was used to input the literatures,and we assessed the risk bias on the level of outcome indicators for each included literature. A total of 18 literatures were included,and the classification results showed that: compared with MTX,TGT alone can reduce the number of joint swelling( MD =0. 18,95%CI[-1.06,1.42],P = 0.78) and joint tenderness( MD =-0.06,95% CI[-1.69,1.56],P = 0.94) in RA patients with the same effect as MTX. In terms of drug combination,TGT combined with MTX had an advantage over MTX alone in lessening the morning stiffness time( MD = 18. 24,95% CI[12. 64,23. 84],P < 0. 000 01) of RA,joint tenderness( MD = 2. 65,95% CI[1. 85,3. 44],P<0.000 01) and joint swelling( MD = 3.01,95% CI[2.09,3.39],P< 0.000 01). In conclusion,this Meta-analysis suggest that TGT alone was superior to MTX in improving joint swelling and tenderness in RA patients,TGT combined with MTX may improve the clinical manifestation of RA patients better than MTX alone.

Meta-analysis of efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine in treatment of chronic urticarial / 中国中药杂志

To analyze the efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine as well as desloratadine alone in the treatment of chronic urticaria by Meta-analysis,in order to provide evidence-based reference for clinical treatment.PubMed,CBM,Wan Fang,VIP database and CNKI database were retrieved to collect randomized controlled trials( RCT) about Tripterygium Glycosides Tablets combined with desloratadine( test group) as well as desloratadine alone( control group) in the treatment of chronic urticaria. Meta-analysis was performed by using Rev Man 5. 3 software after data extraction and quality evaluation( a total of 15 RCTs were included,involving 1 411 patients). Meta-analysis showed that the total effective rate( RR = 1. 28,95%CI[1. 22,1. 35],P<0. 000 01) and the quality of life improvement rate( RR = 1. 49,95% CI[1. 33,1. 66],P< 0. 000 01) of the test group were better than those of the control group,and the recurrence rate( RR = 0. 29,95%CI[0. 21,0. 40],P<0. 000 01) was significantly lower than that of the control group,with statistically significant differences; there was no statistically significant difference in the incidence of adverse reactions( RR = 1. 02,95%CI[0. 68,1. 53],P = 0. 92) compared with the control group. Based on the included RCTs,the efficacy of Tripterygium Glycosides Tablets combined with desloratadine in the treatment of chronic urticaria were superior to those of desloratadine alone,with similarity in safety. However,due to the low quality of RCTs and the lack of large-scale multi-center studies,the results shall not be further verified by clinical trials.

Long-term effect of Tripterygium Glycosides Tablets combined with traditional Chinese medicine on adulthood fertility / 中国中药杂志

To preliminarily investigate the effect of Tripterygium Glycosides Tablets( TGT) combined with traditional Chinese medicine( TCM) on the fertility and female menstruation on persons who have took during childhood. The children with henoch-schonlein purpura( HSP) or henoch-schonlein purpura nephritis( HSPN) who treated with TGT under 18 years old and now older than 18 years old( including 18 years old) during January 1998 to December 2010 were selected in our research. The content of follow-up visit included marriage,marriage age,fertility and child health; and unmarried female patients were asked whether they had menstrual abnormalities. The data of the unmarried female patients,including age,clinical classification,TCM syndrome type,initial dose and other related factors that may affect menstrual cycle,was analyzed by using binary logistic regression analysis. A total of 195 patients who met the criteria were followed up in this study,and 26 patients married for more than 1 year. Among the 26 married patients,1 HSP patient had no birth planning due to rheumatoid arthritis,and the remaining 25 patients all had given birth or were pregnant. The 169 unmarried patients included 89 female patients. Among the 89 female patients,4 cases refused to tell the menstrual situations,72 cases had normal menstruation( 84. 7%),13 cases had abnormal menstruation( 15. 3%),and there was no case of amenorrhea. Logistic regression analysis results showed that the age,clinical classification,TCM syndrome type and initial dose had no correlation with abnormal menstruation. Our results demonstrated that TGT has no effect on adulthood fertility among patients who took TGT combined with traditional Chinese medicine during childhood.

Integrated targeted sphingolipidomics and transcriptomics explore the mechanism of efficacy and toxicity of Tripterygium glycosides tablets on delayed-type hypersensitivity model / 药学学报

Tripterygium glycosides tablets (TGT) have good immunosuppressive activity, but they can also significantly injure the liver and kidney and its mechanism is unclear. In this study, delayed-type hypersensitivity (DTH) Balb/c mouse were administrated with different doses of TGT. Then the changes of sphingolipids levels in live, kidney and plasma as well as the mRNA expression levels of their metabolic enzymes were studied by the integrated targeted sphingolipidomics and transcriptomics methods to reveal the mechanism of efficacy and toxicity of TGT. It was found that low dose of TGT could significantly decrease levels of total ceramide in the plasma, long chain sphingolipids and saturate sphingolipids in the liver and kidney, but increase them in the plasma, which were related to the efficacy mechanism of TGT. High dose of TGT can significantly increase levels of total ceramide, Cer(d18:1/18:0)-1-P, long chain sphingolipids and decrease saturation sphingolipids mechanism. TGT can also cause significant changes of mRNA expression levels of various sphingolipid metabolic enzymes in the liver and kidney, which were correspond to the changes of sphingolipid levels. The efficacy and toxicity of TGT were related to the regulation of these key enzyme expression levels. In conclusion, the efficacy and toxic mechanism of TGT were closely related to the sphingolipids metabolism. A variety of potential biomarkers were found and they can provide valuable information for the evaluation of the efficacy and toxicity of TGT.