ABSTRACT
Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.
ABSTRACT
Objective:To compare the effects and multi-organ intervention of tripterygium glycosides(TG) tablet from Hunan Qianjin Xieli (QJ) and Zhejiang Deende (DED) on type Ⅱ collagen-induced arthritis (CIA) in rats. Method:The 72 SD rats were randomly divided into normal group, model group, QJ TG clinical group 2 times, 6 times equivalent dose group (QJ-TG 0.018, 0.054 g·kg-1), derende TG clinical group 2 times, 6 times equivalent dose group (DED-TG 0.018, 0.054 g·kg-1). The intragastric administration was started on the day after the first immunization, once a day. After the second immunization, the symptoms such as redness and swelling of joints were observed, and the clinical score of arthritis were evaluated. The materials were taken for pathological examination of the inflammatory joints on the 21th and 42th day. The concentration of alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), gamma-glutamyltransferase(GGT), total bilirubin(TBIL), creatinine(CRE) and urea(UREA) in serum were detected by enzymatic assay. The rate of sperm deformity, testicular and ovarian tissue damage in the rat epididymis was assessed. Result:TG from two manufacturers attenuated the inflammation, redness, swelling and deformity of joints in CIA rats, 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. There were significant differences between the QJ-TG high and low dose groups and the DED-TG high dose group compared with the model group (PP-1 group had a significant inhibitory effect on the clinical scores on the 15th and 18th days than the QJ-TG same dose group (P-1 dose of DED-TG, the white blood cell count and spleen index were significantly increased.At the same time, two different manufacturers of TG had no effect on body weight, organ index, digestive system, liver and kidney function, liver and kidney pathology of CIA model rats. QJ-TG and DED-TG all significantly increased the rate of male rats sperm malformation and significant damage to testicular seminiferous tubules and the toxicity increased with the increase of dose and time. while the mole reproductive toxicity of DED-TG was higher than that of QJ-TG at the same dose. In the DED-TG 0.054 g·kg-1 and QJ-TG 0.054 g·kg-1 group, there were only the reduction of vascular distribution in the ovarian tissue and the reduction of the corpus luteum, and no other toxic effects were observed. Conclusion:Two manufacturers TG2 times (0.018 g·kg-1) and 6 times (0.054 g·kg-1) clinical equivalent dose can delay the onset of CIA in rats, reduce the clinical score of arthritis, improve the pathological changes of joints, but have a certain degree of male reproductive toxicity. The high-dose DED-TG is more toxic than the QJ-TG.
ABSTRACT
OBJECTIVE:To study the pharmacokinetics of triptolide in Tripterygium glycosides tablet in normal rats and adju-vant arthritis model rats in vivo,and provide reference for clinical rational drug use. METHODS:12 SD rats were randomly divid-ed into normal group and model group,6 in each group. Model group was subcutaneously injected complete Freund's adjuvant 0.1 mL to induce adjuvant arthritis model,normal group was subcutaneously injected the same volume of saline. After 14 d model-ing,2 groups were given Tripterygium glycosides tablet suspension 96 mg/kg intragastrically,the blood sample of eyes 0.4 mL were respectively taken before and 10,30,45,60,90,120,150,180,240,300,420 min after administration. The plasma con-centration of triptolide was determined by HPLC,the pharmacokinetic parameters were calculated by DAS 2.0 software,and the parameters were compared. RESULTS:The pharmacokinetic parameters of triptolide in normal group were cmax of(1.139±0.114)μg/mL,tmax of(2.167±0.606)h,t1/2α of(5.500±3.610)h,AUC0-7 h of(5.052±0.371)μg·h/mL,MRT0-7 h of(3.224±0.119)h, and CL of(11.616±2.986)mL/h;and those in model group were cmax of(0.916±0.103)μg/mL,tmax of(3.083±0.801)h,t1/2αof(5.593±1.795)h,AUC0-7 h of(4.707±0.347)μg·h/mL,MRT0-7 h of(3.429±0.139)h,and CL of(11.246±2.638) mL/h. Compared with normal group,cmax in model group was significantly decreased,tmax and MRT0-7 h were significantly prolonged(P<0.05). CONCLUSIONS:Adjuvant arthritis can affect the pharmacokinetics of triptolide in rats in vivo,and promote its absorption and removal.
ABSTRACT
OBJECTIVE:To systematically review the efficacy and safety of Ambrette capsule combined with Tripterygium gly-cosides tablet versus Tripterygium glycosides tablet alone in the treatment of diabetic nephropathy to provide evidence-based refer-ence for clinical treatment. METHODS:Retrieved from CJFD,Wanfang database,VIP database,Cochrane Library,EMBase and Medline randomized controlled trials(RCT)about Ambrette capsule combined with Tripterygium glycosides tablet(test group)ver-sus Tripterygium glycosides tablet alone(control group)in the treatment of diabetic nephropathy were collected. Meta-analysis was performed by using Rev Man 5.1 software after data extraction and quality evaluation. RESULTS:A total of 5 RCTs were includ-ed,involving 400 patients. Results of Meta-analysis showed the effective rate [OR=4.10,95%CI(2.27,7.38),P<0.001],24 h uri-nary protein quantificative value[MD=-0.54,95%CI(-0.72,-0.36),P<0.001] in test group were significantly higher than con-trol group,there were statistical significances. alanine aminotransferase value [MD=0.14,95%CI(-1.08,1.36),P=0.82] and changes value of peripheral white blood cells(WBC)[MD=-0.31,95%CI(-0.64,0.03),P=0.07] were not statistical difference between 2 groups. CONCLUSIONS:Efficacy of Ambrette capsule combined with Tripterygium glycosides tablet in the treatment of diabetic nephropathy were superior to Tripterygium glycosides tablet alone with similar safety. Due to limit of methodological quali-ty,more strict,long-term follow-up large-scale RCTs were required to validate the conclusion.
ABSTRACT
OBJECTIVE:To provide for rational use of Tripterygium glycosides tablet clinically. METHODS:The utilization of Tripterygium glycosides tablet were collected from hospital information system(HIS)in our hospital during Jun. 2012-Jun. 2014. Then the data about the basic information,patients’age,departments and diagnosis,were analyzed by the Excel. RESULTS:The application of Tripterygium glycosides tablet remained stable since Jun. 2012. There were 4 600 prescriptions in average every year, and the age of patients was distributed from 11 to 90. Tripterygium glycosides tablet was mainly used in rheumatology department (52.11%),followed by TCM rheumatology department(20.62%),skin disease and venereal disease department(18.15%),ne-phrology department(3.52%)and integrated traditional and western medicine cardiology department(1.77%). It was mainly used to treat rheumatoid arthritis,Sjogren's syndrome,polymyalgia rheumatica,osteoporosis and nephrotic syndrome. CONCLUSIONS:The application of Tripterygium glycosides tablet as immunosuppressant is widely used,but the age of patient is with wide distribu-tion;the narrow gap exists between minimum effective dose and minimum lethal dose;so ADR should be concerned closely.
ABSTRACT
OBJECTIVE:To investigate the clinical efficacy of integrated treatment of traditional Chinese medicine and west-ern medicine for subacute thyroiditis. METHODS:98 patients with subacute thyroiditis were randomly divided into control group and observation group by random number table with 49 patients in each group. Control group was given conventional oral treat-ment of prednisone tablets,and observation group was additionally treated with Chinese patent medicine(Shuanghuanglian oral so-lution+Antiviral oral solution+Tripterygium glycosides tablet)on the basis of control group. A treatment course lasted for 4 weeks, and both groups received 2 courses of treatment. Therapeutic efficacy,symptom and sign improvement time,total treatment course,recurrence rate and ADR were observed and compared between 2 groups. RESULTS:the total effective rate of observation group was 100%,significantly better than the control group 79.59%,and there were significant differences(P<0.01). The defer-vescence time,thyroid pain recovery time,thyroid swelling fadeaway and total treatment course of observation group was shorter than those of control group,with statistical significance(P<0.01). Following up 2 months after drug withdrawal,the recurrence rate of observation group was 6.12%,which was significantly lower than that of control group(22.45%),with statistical signifi-cance (P<0.05). Small number of ADR occurred in 2 groups. CONCLUSIONS:The integrated treatment of traditional Chinese medicine and western medicine for subacute thyroiditis can control the symptom rapidly,reduce the possibility of palindromia and reduce ADR.
ABSTRACT
Objective To investigate the clinical efficacy of Bushen Tongdu Capsule for treating patients with rheumatoid arthritis (RA, TCM syndrome of kidney-deficiency with cold). Methods Totally 71 RA patients were randomly divided into treatment group (36 cases) that was treated with Bushen Tongdu Capsule and control group (35 cases) that was treated with tripterygium glycosides tablet. Both groups were treated for 12 weeks. The signs and symptoms, the state of illness, and laboratory index were observed before and after treatment. Results The total effective rate was 72.22% (26/36) in the treatment group, and 62.86% (22/35) in the control group, without statistical significance (P>0.05). After treatment, simplified disease activity index, TCM syndrome integrals, tender joint count, swollen joint count, overall evaluation from patients, overall disease evaluation from doctors, rest pain, morning stiffness time, average hands grip strength, 20 m walking time, healthy condition questionnaire score, and C-reactive protein were significantly improved in both groups (P<0.01, P<0.05). Compared with control group, TCM syndrome integrals changed more significantly, with statistical significance (P <0.05). Conclusion Bushen Tongdu Capsule can relieve symptoms and signs of RA patients (TCM syndrome of kidney-deficiency with cold) effectively.