title: Evaluation of the efficacy and safety of different Tripterygium preparations on collagen-induced arthritis in rats.
abstract: BACKGROUND
  Tripterygium preparations (TPs), a traditional Chinese Medicines extracted from Tripterygium wilfordii Hook f., are widely used for treatment of rheumatoid arthritis (RA). However, TPs from different Pharmaceutical factory have different efficacy and side effects for RA treatment.
  
  
  OBJECTIVE
  The purpose of the current study is to evaluate the efficacy and safety of four TPs from different Pharmaceutical factory in china on the treatment of collagen-induced arthritis (CIA) rats and provide a theoretical and experimental basis for the individualized use of TPs.
  
  
  METHODS
  The model of wistar rats of CIA was made, and the rats were perfused a stomach with four TPs for 3 weeks continuously. Then arthritis severity was determined by visual examination of the paws and histopathologic changes of joint, liver, kidney and testis were determined by hematoxylin-eosin (H&E) staining. The expression of inflammatory cytokines (IL-1β, TNF-α, IL-17 and IL-6) in the joint was analyzed by real-time PCR, and the count and motion parameters (sperm motility and progressive sperm) of sperm in cauda epididymis were assessed with computer-assisted sperm analysis (CASA) system. Routine blood tests were conducted using automated hematology analyzer, and the aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, creatinine (Cr), and blood urea nitrogen (BUN) in serum of CIA rats were measured using a UniCel DxC 880i autoanalyzer.
  
  
  RESULTS
  All of tested TPs could reduce inflammatory score, histopathological arthritis severity and joint׳s inflammatory cytokines (IL-1β, TNF-α, IL-17 and IL-6) expression in CIA rats, however, TP-D showed stronger inhibitory effect for inflammatory score compared with other three TPs in vivo. All of tested TPs did not show hepatotoxicity and nephrotoxicity and also had little effect for the concentration of hemoglobin (Hb) and the count of white blood cell (WBC). Analysis of red blood cell (RBC) number showed that TP-C and TP-D could reverse lower RBC number in untreated CIA rats to normal level. Interestingly, the results showed TPs named TP-C and TP-D could decrease platelet (PLT) number which significantly increases in untreated CIA rats. Reproductive toxicity, the main side effect of TPs, assay showed that the sperm quality (density, viability, and motility) in four of TPs-treated CIA rats were decreased significantly, consistently with spermatogenic cell density reduced. However parallel analysis showed that in four TPs-treated rats, the number of sperm, motile sperm and progressive sperm were highest in TP-D group, in contrast, were lowest in TP-C group.
  
  
  CONCLUSIONS
  These findings suggested that four TPs showed significantly therapeutic effect on ameliorating inflammation of CIA rats, with no obvious hepatotoxicity and nephrotoxicity in vivo. TP-D showed advantages with its higher efficacy and less reproductive toxicity as well as increasing RBC number, decreasing PLT number in CIA treatment. Thus, in the development of individualized treatment plan for RA patients, TP-D might be considered preferentially.
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Affiliated Union Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Xianjin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Rongfen
authors.initials: R
authors.lastname: Huo
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jinpiao
authors.initials: J
authors.lastname: Lin
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Pinru
authors.initials: P
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huidan
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tianhang
authors.initials: T
authors.lastname: Zhai
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Baihua
authors.initials: B
authors.lastname: Shen
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: ninglixiaoxue57@163.com.
authors.forename: Ningli
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000517:prevention & control*; D001483:Base Sequence; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D029757:Tripterygium / Q000737:chemistry*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D010936:Plant Extracts
keywords: Collagen-induced arthritis (CIA) rats; Reproductive toxicity; Rheumatoid arthritis; Tripterygium preparations