Liposome-encapsulated dimethyl curcumin inhibits over-activation of rat lymphocyte to relieve collagen-induced arthritis by regulating intracellular proteolysis and PCNA/p21/caspase-3 pathway

Dimethyl curcumin,a synthetic derivative of curcumin,has good anti-cancer,anti-arthritis and anti-inflammatory properties,but underline mechanism was unclear.Activation,differentiation,proliferation and apoptosis of lymphocytes have important functions during arthritis development and immune homeostasis.Over-activation of lymphocyte causes inflammatory cytokines storm,leading to an immune imbalance and tissue damages.The aim of this study was to investigate the anti-inflammation mechanism of liposome encapsulated dimethyl curcumin(Lipo-DiMC)on over-activated rat spleen lymphocytes.In this study,Lipo-DiMC was produced to increase the solubility;the primary rat spleen lymphocytes were extracted and the Concanavalin A induced cell activation model was established to study the cellular responses to Lipo-DiMC treatment in-vitro.The results showed that Lipo-DiMC suppressed Concanavalin A-induced cell proliferation,inhibited cells entering G2/M phase,and reduced the ratio of necrosis/apoptosis by manipulating intracellular p53/p21/PCNA/JNK-1 pathways.Furthermore,Lipo-DiMC increased the accumulations of intracellular matrix metalloproteinase-9 and reduced matrix metalloproteinase-9 secretion of rat spleen lymphocytes.Also,Lipo-DiMC increased intracellular caspase-3 expression and reduced Cat-C activity in activated rat spleen lymphocytes,involving in intracellular proteolysis.Our findings suggest that dimethyl curcumin effectively alleviates Concanavalin A induced over-activation of rat spleen lymphocytes,thereby inhibiting inflammatory cytokines storm and restoring cell homeostasis.

Detraining after tumor-bearing accelerates tumor growth while continuous training decreases tumor growth in mice

Objective:Previous studies have shown that exercise suppresses tumor growth.However,the effects of exercise with different intensities and exercise detraining after tumor-bearing on tumor progression remain unclear.The purpose of this study was to investigate the effects of continuous and disrupted free and exhausted swimming training after tumor-bearing on tumor progression in melanoma B16-F10-bearing C57BL/6 mice.Methods:C57BL/6 mice were subjected to free or exhausted swimming exercise training for 4 weeks prior to the injection of melanoma B16-F10 cells.Subsequently,the B16-F10-bearing mice were maintained with training consisting of free or exhausted swimming or without exercise for 2 weeks during the tumor challenge.Results:The tumor weight was increased by 42%and 109%in mice with 4-week exhausted swimming prior to B16-F10 tumor cells inoculation followed by 2-week training cessation compared with the tumor-bearing control(P<.05)and continuous training groups(P<.01).Tumor weights in groups with exercise detraining after tumor cell inoculation tended to be increased,while the proliferation of splenic T lymphocytes tended to be decreased compared with the group that maintained exercise intensity.After 6-weeks continuous free or exhausted swimming training,the tumor weight of mice was decreased and the proliferation of splenic T lymphocytes was increased compared with the tumor-bearing control group.The frequency of natural killer cells in tumors was increased in all exercise training groups of mice.Conclusions:These results suggest that maintaining exercise intensity after tumor-bearing slows tumor growth in mice,possibly because of the enhanced proliferative activity of splenic lymphocytes rather than natural killer cell infiltration.However,detraining after tumor-bearing might accelerate tumor progression because of the reduced proliferation of splenic T lymphocytes.

A novel arctigenin-containing latex glove prevents latex allergy by inhibiting typeⅠ/Ⅳallergic reactions

The present study aimed at developing a natural compound with anti-allergic effect and stability under latex glove manufacturing conditions and investigating whether its anti-allergic effect is maintained after its addition into the latex. The effects of nine natural compounds on growth of the RBL-2H3 cells and mouse primary spleen lymphocytes were determined using MTT assay. The compounds included glycyrrhizin, osthole, tetrandrine, tea polyphenol, catechin, arctigenin, oleanolic acid, baicalin and oxymatrine. An ELISA assay was used for the in vitro anti-type I/IV allergy screening; in this process β-hexosaminidase, histamine, and IL-4 released from RBL-2H3 cell lines and IFN-γ and IL-2 released from mouse primary spleen lymphocytes were taken as screening indices. The physical stability of eight natural compounds and the dissolubility of arctigenin, selected based on the in vitro pharnacodynamaic screening and the stability evaluation, were detected by HPLC. The in vivo pharmacodynamic confirmation of arctigenin and final latex product was evaluated with a passive cutaneous anaphylaxis(PCA) model and an allergen-specific skin response model. Nine natural compounds showed minor growth inhibition on RBL-2H3 cells and mouse primary spleen lymphocytes. Baicalin and arctigenin had the best anti-type I and IV allergic effects among the natural compounds based on the in vitro pharmacodynamic screening. Arctigenin and catechin had the best physical stability under different manufacturing conditions. Arctigenin was the selected for further evaluation and proven to have anti-type I and IV allergic effects in vivo in a dose-dependent manner. The final product of the arctigenin-containing latex glove had anti-type I and IV allergic effects in vivo which were mainly attributed to arctigenin as proved from the dissolubility results. Arctigenin showed anti-type I and IV allergic effects in vitro and in vivo, with a good stability under latex glove manufacturing conditions, and a persistent anti-allergic effect after being added into the latex to prevent latex allergy.