ABSTRACT
BACKGROUND:Mangiferin is a biphenylpyridone compound extracted from mango leaves,bark and roots.Previous studies have shown that mangiferin can exert anti-systemic inflammatory effects through the activation of transcription factors such as NF-κB and JAK/STAT. OBJECTIVE:To investigate the effects and mechanisms of mangiferin on proliferation,migration and inflammatory factor release of rheumatoid arthritis fibroblast-like synovial cells(RA-FLS). METHODS:RA-FLS were divided into blank group,R848(TLR7/8 agonists)stimulated group,mangiferin low-,medium-,high-dose groups(2,4 and 8 μg/mL)and positive control group(Cu-CPT8,TLR8 pathway inhibitor).The cytotoxic effect of different mass concentrations of mangiferin was detected using cell counting kit-8 method and the final cellular dosing mass concentration was screened.The proliferation ability of RA-FLS was detected by cell clone formation assay,the migration ability of RA-FLS was detected by scratch assay and Transwell migration assay,and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA in RA-FLS was detected by qRT-PCR. RESULTS AND CONCLUSION:Compared with the blank group,the viability of RA-FLS was inhibited after treatment with mangiferin at 2-10 μg/mL,but there was no significant difference among groups(P>0.05),indicating that the toxic effect on RA-FLS was minimal.Compared with the R848-stimulated group,mangiferin decreased the number of cell clones,the scratch healing rate and the number of migrating cells in all dosing groups(P<0.01);and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA was also reduced in the mangostin medium-and high-dose groups(P<0.01).Compared with the R848-stimulated group,the number of cell clones,the scratch healing rate and the number of migrating cells as well as the expression levels of interleukin 6 and tumor necrosis factor α mRNA were significantly reduced in the positive control group(P<0.05,P<0.01).But there was no significant difference in the expression level of interleukin 1β.To conclude,mangiferin may exert its anti-rheumatoid arthritis effects through the TLR7/8 signaling pathway by inhibiting RA-FLS proliferation,migration,and inflammatory factor release.
ABSTRACT
ObjectiveTo observe the primary tumor of tree shrews and to provide a basis for studying the pathogenesis and prevention of trichoepithelioma. MethodsA tumor was discovered in the chest and abdomen of a tree shrew during natural cultivation. The tree shrew was anesthetized, and the tumor was surgically removed. Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed on the tumor tissue after paraffin section, and the tumor cells were isolated and cultured by passage. The isolated tumor cells were subcutaneously injected into healthy tree shrews and nude mice. The tumorigenesis of tumor cells in vivo was observed once a day, with nude mice continuously observed for 2 months and tree shrews observed for more than 6 months. ResultsHE staining showed that the basal cells in the dermis were arranged as a whole, like a string of petals, forming nests and stripe-like structures with clear boundaries. The observation results after magnification revealed that the tumor cells were arranged in a pallisade-like and basal pattern, with deep nuclear staining and minimal cytoplasmic. Immunohistochemical staining showed the high expression of CK protein and low proportion expression of ki-67 protein in tumor cells, as well as the high expression of vimentin and low expressions of Bcl2 and CD10 in tumor cell mesenchyme. The isolated tumor cells grew well in DMEM medium containing 10% fetal bovine serum and could be cultured by passage, but no tumor formation was observed in healthy tree shrews and nude mice inoculated with tumor cells. ConclusionCombined with the location of the tumor, overall morphology, HE staining, and immunohistochemical results, the thoracoabdominal mass of the tree shrew was diagnosed as a trichoepithelioma.
ABSTRACT
Aim To investigate the combined effect of mangiferin and ephedrine as well as explore its underlying mechanism in mouse model of allergic asthma.Methods The mouse model of asthma was sensitized and challenged with ovalbumin(OVA).The behaviors of mice during the challenging period were observed.Continuous autonomic activities of mice after 1 h of drug treatment were monitored with the autonomic activity recorder for 14 days.The total and differential cells in peripheral blood were counted.Histological study of lung sections on airway inflammation was carried out with haematoxylin and eosin(HE) staining.The levels of ovalbumin-specific immunoglobulin E(OVA-sIgE) and(Cyclic Adenosine monophosphate) cAMP in serum were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA expression of cytokines mainly produced by Th1/Th2 lymphocytes such as IFN-γ and IL-4, IL-5 were semi-quantitatively analyzed with reverse transcription polymerase chain reaction(RT-PCR).Results Combination treatment and mangiferin could reduce the aberrantly autonomic activity caused by ephedrine in mice.Compared with the model group, asthmatic symptoms in all treatment groups could be significantly relieved, the pathological changes of lung tissue were improved and airway inflammation was reduced.The effect of combined treatment was better than that of mangiferin treatment alone.Compared with the model group, the total number of white blood cells(WBC) and the eosinophils(EOS) ratio in peripheral blood in all treatment groups decreased, the level of OVA-sIgE declined and the level of cAMP increased in serum.Combination treatment could lower mRNA expressions of IL-4 and IL-5 from Th2 lymphocytes and increase the mRNA expressions of IFN-γ released by Th1 lymphocytes.Conclusions The effect of combined therapy of mangiferin and ephedrine is better than that of mangiferin treated alone, meanwhile it can reduce the side effects caused by ephedrine.The underlying mechanism is mainly associated with attenuating Th1/Th2 cytokine imbalance and increasing the level of cAMP.
