Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes

Objective:To determine the role of Tripterygium wilfordii multiglycoside(TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.Methods:Mouse models of psoriatic dermatitis were established by imiquimod(IMQ).Twelve male BALB/c mice were assigned to MQ or IMQ+TGW groups according to a random number table.Histopathological changes in vivo were assessed by hematoxylin and eosin staining.Ratios of immune cells and cytokines in mice,as well as PAM212 cell proliferation in vitro were assessed by flow cytometry.Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.Results:TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45^(+)cells,neutrophils and T lymphocytes(all P<0.01).Moreover,TGW significantly attenuated keratinocytes(KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin(IL)-17A,IL-23,tumor necrosis factor α,and chemokine(C-X-C motif) ligand 1(P<0.01 or P<0.05).Furthermore,it reduced the number of γδ T17 cells in skin lesion of mice and draining lymph nodes(P<0.01).Conclusions:TGW improved psoriasis-like inflammation by inhibiting KCs proliferation,as well as the associated immune cells and cytokine expression.It inhibited IL-17 secretion from γδ T cells,which improved the immune-inflammatory microenvironment of psoriasis.

Tripterygium wilfordii multiglycoside-induced hepatotoxicity via inflammation and apoptosis in zebrafish

Tripterygium wilfordii multiglycoside(GTW)is a commonly used compound for the treatment of rheumatoid arthritis(RA)and immune diseases in clinical practice.However,it can induce liver injury and the mechanism of hepatotoxicity is still not clear.This study was designed to investigate GTW-induced hepatotoxicity in zebrafish larvae and explore the mechanism involved.The 72 hpf(hours post fertilization)zebrafish larvae were administered with different concentrations of GTW for three days and their mortality,malformation rate,morphological changes in the liver,transaminase levels,and histopathological changes in the liver of zebrafish larvae were detected.The reverse transcription-polymerase chain reaction(RT-PCR)was used to examine the levels of microRNA-122(miR-122)and genes related to inflammation,apoptosis,cell proliferation and liver function.The results showed that GTW increased the mortality of zebrafish larvae,while significant malformations and liver damage occurred.The main manifestations were elevated levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),significant liver atrophy,vacuoles in liver tissue,sparse cytoplasm,and unclear hepatocyte contours.RT-PCR results showed that the expression of miR-122 significantly decreased by GTW;the mRNA levels of inflammation-related genes il1β,il6,tnfα,il10,cox2 and ptges significantly increased;the mRNA level of tgfβsignificantly decreased;the mRNA levels of apoptosis-related genes,caspase-8 and caspase-9,significantly increased;the mRNA level of bcl2 significantly decreased;the mRNA levels of cell proliferation-related genes,top2αand uhrf1,significantly reduced;the mRNA levels of liver function-related genes,alr and cyp3c1,significantly increased;and the mRNA level of cyp3a65 significantly decreased.In zebrafish,GTW can cause increased inflammation,enhanced apoptosis,decreased cell proliferation,and abnormal expression of liver function-related genes,leading to abnormal liver structure and function and resulting in hepatotoxicity.

HISTOCHEMICAL EFFECT OF THE MULTIGLYCOSIDES OF TRIPTERYGIUM WILFORDII HOOK.F.(GTW)ON THE TESTIS AND EPIDIDYMIS OF RATS

SD Twenty adult male rats were equally divided into a contro1 and an experimcntal group.GTW,10 mg/kg per day,was given to the experimental rats through gastric gavage 6 days a week for 8 weeks.To the control rats,the same amount of vehicle was given The animals were sacrificed when they became infertile and the fol1owing parameters of the testis and epididymis were examined:l)DNA(Feulgen′s method),2)RNA(Brachet′s tech-uique),3)LDH-X(Lojda′s method),4)ATPase(Wachstein′s procedure),5)Succinate dehydrc-genase(SDH,Pearson's method),6)Non-specific esterase(NSE,Lojda's technique)and 7)PAS reaction.Routine examination of the epididymal spermatozoa was also carried out.