Role of nuclear factor-kappaB on emodin-induced sensitization of pancreatic cancer to gemcitabine / 药学学报

In view of gemcitabine resistance has limited clinical activity of gemcitabine as a cellulotoxic drug in pancreatic cancer patients, this study is designed to investigate the effect of emodin on the sensitivity of pancreatic cancer to gemcitabine as well as its mechanism. After gemcitabine-resistant pancreatic cancer cell line (SW1990/GZ) was established by escalating doses of gemcitabine serially in pancreatic cancer cell line (SW1990). The cellular proliferation was detected by cell counting kit-8 (CCK-8) assay. Flow cytometry (FCM) was used to determine apoptosis of pancreatic cancer cells. The activity of NF-kappaB in pancreatic cancer cells was measured by electrophoretic mobility shift assay (EMSA). Western blotting was used to detect the protein expression of Bcl-2 and Survivin in SW1990/GZ cells. Metastatic model simulating human pancreatic cancer was established by orthotopic implantation of histologically intact human tumor tissue into pancreatic wall of nude mice. Also, immunohistochemistry was used to detect the positive expression of Ki-67, NF-kappaB, Bcl-2 and Survivin in the tumors. The results show that pretreatment of cells with emodin followed by gemcitabine induced a higher percentage of growth inhibition and apoptosis of pancreatic cancer cells than that of gemcitabine alone. In addition to in vitro results, emodin in combination with gemcitabine is much more effective as an antitumor agent compared to either agent alone in the orthotopic tumor model. Further study showed that the emodin with or without gemcitabine significantly down-regulates NF-kappaB and its regulated molecules such as Bcl-2 and Survivin proteins both in vitro and in vivo. It is concluded that inactivation of NF-kappaB signaling pathway by emodin resulting in the chemosensitization of pancreatic cancer to gemcitabine, which is likely to be an important and novel strategy for the treatment of pancreatic cancer.

Effect of emodin in suppressing acute rejection following liver allograft transplantation in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of action of emodin for suppressing acute allograft rejection in a rat model of liver transplantation.</p><p><b>METHODS</b>Brown Norway (BW) recipient rats of orthotopic liver transplantation (OLT) were divided into three groups, Group A receiving isografting (with BW rats as donor), Group B receiving allografting (with Lewis rats as donor), Group C receiving allografting and emodin treatment (50 mg/kg daily). They were sacrificed on day 7 of post-transplantation, and their hepatic histology, plasma cytokine levels, and T-cell subset expression were detected.</p><p><b>RESULTS</b>Compared with those in Group A, rats: in Group B exhibited severe allograft rejection with a rejection activity index (RAI) of 7.67+/-0.98, extensive hepatocellular apoptosis with an apoptosis index (AI) of 35.83+/-2.32, and elevated plasma levels of interleukin-2 (IL-2), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), CD4(+) and CD4 CD4(+)/CD8(+) ratio. However, recipients in Group C showed a decrease in histological grade of rejection and hepatocellular apoptosis, as well as a decrease in plasma levels of IL-2, TNF-alpha, CD4(+) and CD4(+)/CD8(+) ratio, but elevated levels of IL-10 as compared with the allograft group.</p><p><b>CONCLUSION</b>Post-OLT acute rejection could be attenuated by emodin, its mechanism of action may be associated with protecting hepatocytes from apoptosis, polarizing the Th 1 paradigm to Th2, and inhibiting the proliferation of CD4(+) T cell in plasma.</p>

Inhibitory effect of emodin on the differentiation and maturation of dendritic cells in vitro / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of emodin on the differentiation, maturation and function of human dendritic cells (DC) in vitro.</p><p><b>METHODS</b>Cells isolated from human peripheral blood mononuclear cells (PBMCs) were induced to dendritic cells (DC) with recombinant interleukin-4 and recombinant granulocyte-macrophage colony stimulating factor (GM-CSF). Lipopolysaccharide (LPS) and different concentrations of emodin were added respectively in the cultured cells on the 5th and the 7th to obtain mature or immature DCs. The phenotype of DCs ( HLA-DR, CD80, CD86, CD83, CD14, CD11c) and the secretion of interleukin-12 (IL-12) were analyzed by flow cytometry, and the immune-stimulating function of DCs was evaluated by co-culture of DCs and self-T-lymphocytes.</p><p><b>RESULTS</b>The expression rate of CD80 and CD83 in the emodin group were 13.4% +/- 6.6% and 9.3% +/- 2.2% respectively; which were significantly lower than those in the control group (39.3% +/- 8.6% and 30.7% +/- 5.6%), respectively (P<0.05). IL-12 secretion of DCs was lower (1700.44 +/- 1000.21 microg/L vs 4500.60 +/- 1200.6 microg/L) but IL-10 secretion was higher (350.6 +/- 150.2 microg/L vs 230.7 +/- 90.1 microg/L) in the emodin group than in the control group (P<0.05). Mixed lymphocyte culture (MLR) examination showed that emodin could significantly inhibit the stimulation of DCs on self-T-lymphocyte proliferation.</p><p><b>CONCLUSION</b>Emodin could evidently suppress the maturation and immune stimulating function of DCs during their in vitro conversion process.</p>

Synergistic effect of emodin and cyclosporine A on rejective reaction against liver graft in rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the effect of emodin in combination with cyclosporine A (CsA) on rejective reaction against liver graft in rats.</p><p><b>METHODS</b>The LEW-->BN orthotopic liver transplantation rat model was used in the study. A total of 48 rats were divided into 4 groups randomly and equally, after operation they were intraperitoneally injected respectively with normal saline (0.5 mL d(-1), group A); CsA (10.0 mg kg(-1) d(-1), group B); emodin (50.0 mg kg(-1) d(-1), group C); and CsA plus emodin (group D, at the same dose as in B and C). Six rats taken from each group were sacrificed on the 8th day after operation to calculate the rejection active index (RAI) and hepatocyte apoptosis index (AI). The remainder were stopped medication and used for observing the survival time.</p><p><b>RESULTS</b>The inter-group comparisons in mean survival time, RAI and AI showed significant difference in comparing group A with group B, C and D (P <0.01), and those in group D were more obvious than in group B and C (P < 0.05, but showed no significant difference between group B and group C (P > 0.05).</p><p><b>CONCLUSION</b>Administering of emodin combined with CsA after liver transplantation shows a synergistic effect for suppressing acute rejective reaction in rats.</p>

Effect of emodin on hepatocellular apoptosis following orthotopic liver transplantation in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the effect of emodin on hepatocellular apoptosis following orthotopic liver transplantation (OLT) in rats.</p><p><b>METHOD</b>The LEW --> BN OLT models were established. A total of 24 rats were divided randomly and equally into 4 groups. Group A was treated with normal saline at dose of 0.5 mL x d(-1) intraperitoneally from 1st day to 8 th day after operation. Group B, CsA at dose of 10.0 mg x kg(-1) x d(-1). Group C, emodin at dose of 50.0 mg x kg(-1) x d(-1). Group D, CsA at dose of 10.0 mg x kg(-1) x d(-1) and emodin at dose of 50.0 mg x kg(-1) x d(-1). Fifteen days after operation, rejection active index (RAI) and hepatocellular apoptosis index (AI) was confirmed after observing the pathologic change of transplanted liver in recipients.</p><p><b>RESULT</b>Respectively, the RAI of group A, B, C, D was 7.67 +/- 0.98, 5.17 +/- 0.40, 5.83 +/- 0.75, 3.83 +/- 0.75 and the AI of group A, B, C, D was 35.83 +/- 2.320, 15.83 +/- 1.33, 16.50 +/- 2.35, 11.50 +/- 1.05. The RAI and AI of group B, C, D was significantly lower than group A (P < 0.01) and group D was significantly lower than group B, C too (P < 0.05). There was no significant distinction between group B and C in RAI and AI.</p><p><b>CONCLUSION</b>Emodin has the effect of reduce the hepatocellular apoptosis following OLT in rats and the effect can stronger by CsA.</p>

Experimental advance of applying emodin for prevention and treatment of liver diseases / 中国中西医结合杂志

The experimental researches of applying emodin for prevention and treatment of liver diseases in recent years were reviewed. Emodin can inhibit the growth of liver tumor cells in vitro and in vivo, inducing cell apoptosis is one of its mechanisms. Emodin also has the effects of liver protection, anti-liver fibrosis, and so on, the mechanisms for those effects still need more studies.