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OBJECTIVE@#To investigate the effects of matrine on antigen presentation of dendritic cells (DCs), and to explore the pharmacological mechanism of matrine on anti-tumor effect.@*METHODS@#Different concentrations (0, 1, 2, 4, 8 and 16 µ g/mL) of matrine were co-cultured with DCs, the harvested DCs were co-cultured with antigens of Lewis lung cancer (LLC) cells, and then DCs and T cells were co-cultured to produce DCs-activated killer (DAK) cells, which have significant tumor-killing activity. The expression of cytokines, mRNA and protein of toll-like receptors (TLRs) in DCs were detected by enzyme linked immunosobent assay, polymerase chain reaction and Western blot, respectively. And the killing effect of DAK were measured by MTT assay.@*RESULTS@#Matrine significantly increased the mRNA expression of TLR7, TLR8, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6) and I κ B kinase (IKK), as well as the protein expression of TLR7 and TLR8, and up-regulated the levels of interleukin-12 (IL-12), IL-6 and tumor necrosis factor-α (TNF-α), meanwhile, it also increased the expressions of MHC-II, CD54, CD80 and CD86 in DCs. DCs-activated effector T cells had significant tumor-killing activity. When the concentration of matrine was more than 4 µg/mL, all indices had significant difference (P<0.01 or P<0.05).@*CONCLUSION@#Matrine plays an anti-tumor role by regulating TLRs signal transduction pathway, promoting the secretion of inflammatory cytokines and enhancing immune function.
ABSTRACT
OBJECTIVE@#To explore whether Panax notoginseng saponins (PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved.@*METHODS@#MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water, n=9), MI group (distilled water, n=9), PNS group (PNS, 40 mg/kg daily, n=9) and fosinopril group (FIP, 1.2 mg/kg daily, n=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP), tumor necrosis factor α (TNF-α), growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3), mitogen-activated protein kinase kinase 3 (MAP2K3), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation of p38 MAPK (p-p38 MAPK), transforming growth factor-β (TGF-β1), collagen I, nuclear factor kappa B p65 (NFκB p65), phosphorylation of NFκB p65 (p-NFκB p65), and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining, respectively.@*RESULTS@#PNS improved cardiac function and fibrosis in MI rats (P<0.05). The serum levels of CRP, TNF-α, GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-β1, collagen I, MAP2K3, p38 MAPK, p-p38 MAPK, NFκB p65, p-NFκB p65, and p-IκBα were down-regulated, while ATF3 increased with the treatment of PNS (P<0.05).@*CONCLUSIONS@#PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.
ABSTRACT
Objective: To observe effect of Mori Folium-containing serum on glucose consumption and cell activity of fat cell line 3T3-L1 insulin resistance (IR) model, in order to screen out the optimal concentration of drug-containing serum, detect effect of Mori Folium on the content of inflammatory factors, and explore the possible mechanism. Method: 3T3-L1 preadipocytes in logarithmic growth phase were selected, and induced with 10 mg·L-1 insulin (Ins), 0.25 mmol·L-1 dexamethasone (DEX) and 0.5 mmol·L-1 3-isobutyl-methylxanthine(IBMX) for 48 h and then with 10 mg·L-1 Ins for 48 h. After the cells were differentiated into mature adipocytes, they were induced with 1 μmol·L-1 DEX for 96 h to establish IR model. Glucose content in the supernatant of cells was detected by glucose oxidase after serum containing Mori Folium cultured for 12,24,36, 72 h. Methyl-thiazdyl-tetrazolium(MTT) was used to detect the effect of serum containing Mori Folium on IR cells activity. The content of tumor necrosis factor-α(TNF-α) was determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the effects of inflammatory factors on the expressions of insulin signaling pathway proteins insulin receptor (InsR), insulin receptor substrate (IRS), p-IRS1 and glucose transporter 4 (GLUT4) were determined by Western blot. Result: Serum containing Mori Folium could significantly increase the glucose consumption rate and cell activity of IR cells (Pα (PPPConclusion: Mori Folium can significantly improve IR status of 3T3-L1 cells, and its mechanism may be related to inhibiting TNF-α and promoting the expressions of insulin signaling pathway proteins.