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
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.