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Significant Inhibitory Effects (significant + inhibitory_effects)
Selected AbstractsRole of four major components in the effect of Si-Ni-San, a traditional Chinese prescription, against contact sensitivity in miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2006Li Zhang Previously, we demonstrated the inhibitory effects of Si-Ni-San, a traditional Chinese prescription, on picryl chloride-induced ear contact sensitivity (PCl-CS). This study aimed to evaluate the role of the four major constituents contained in the prescription (saikosaponins, paeoniflorin, naringin and glycyrrhizin) in the inhibitory effect. When administered during the induction phase, saikosaponin a and glycyrrhizin showed significant inhibitory effects, while paeoniflorin and naringin did not. These components in Si-Ni-San also inhibited the activation and proliferation of T lymphocytes as well as the production of cytokines such as tumour necrosis factor-, and interferon-, to different extents. Saikosaponin a and paeoniflorin dose-dependently reduced the splenocyte adhesion to type I collagen, while glycyrrhizin only showed a slight tendency. Furthermore, treatment with glycyrrhizin or saikosaponin a, rather than paeoniflorin or naringin, moderately inhibited the matrix metalloproteinase (MMP)-2 activity of the splenocytes from PCl-CS mice, and the combination of all four components showed a strong inhibition against MMP-2. Moreover, the components markedly decreased the serum level of nitric oxide in PCl-sensitized mice. The results indicated that saikosaponin a and glycyrrhizin may be the major contributors in the alleviation effect of Si-Ni-San on contact sensitivity, and paeoniflorin and naringin may exhibit a co-operative effect. [source] Enhanced antiviral effect in cell culture of type 1 interferon and ribozymes targeting HCV RNAJOURNAL OF VIRAL HEPATITIS, Issue 6 2001D. G. Macejak We have recently shown that the replication of an HCV-poliovirus (PV) chimera that is dependent upon the hepatitis C virus (HCV) 5, untranslated region (UTR) can be inhibited by treatment with ribozymes targeting HCV RNA. To determine the antiviral effects of anti-HCV ribozyme treatment in combination with type 1 interferon (IFN), we analysed the replication of this HCV-PV chimera in HeLa cells treated with anti-HCV ribozyme and/or IFN-,2a, IFN-,2b, or consensus IFN. The anti-HCV ribozyme, or any of the IFNs alone have significant inhibitory effects on HCV-PV replication compared to control treatment (, 85%, P < 0.01). The maximal inhibition due to IFN treatment (94%, P < 0.01) was achieved with , 50 U/ml for either IFN-,2a or IFN-,2b compared to control treatment. A similar level of inhibition in viral replication could be achieved with a 5-fold lower dose of IFN if ribozyme targeting the HCV 5, UTR was given in combination. For consensus IFN, the dose could be reduced by > 12.5-fold if ribozyme targeting the HCV 5, UTR was given in combination. Conversely, the dose of ribozyme could be reduced 3-fold if given in combination with any of the IFN preparations. Moreover, treatment with low doses (1,25 U/mL) of IFN-,2a, IFN-,2b, or consensus IFN in combination with anti-HCV ribozyme resulted in > 98% inhibition of HCV-PV replication compared to control treatment (P < 0.01). These results demonstrate that IFN and ribozyme each have a beneficial antiviral effect that is augmented when given in combination. [source] Ecology-based screen identifies new metabolites from a Cordyceps -colonizing fungus as cancer cell proliferation inhibitors and apoptosis inducersCELL PROLIFERATION, Issue 6 2009Y. Chen Objectives:, This study aims to identify new anti-cancer agents from Cordyceps -colonizing fungi, using an ecology-based approach. It also aims to explore their anti-cell proliferative mechanisms, and to evaluate their anti-tumour effects in vivo. Materials and methods:, Extracts from Cordyceps -colonizing fungi were tested on HeLa cells, and active extracts were separated to obtain anti-tumour metabolites; their structures were elucidated by mass and nuclear magnetic resonance spectroscopy. Cell cycle analysis was evaluated using flow cytometry. Tumour formation assays were performed using C57BL/6J mice. Results:, Based on ecological considerations, the selected extracts were subjected to initial anti-tumour screening. Bioassay-guided fractionation of the active extract afforded two new epipolythiodioxopiperazines, named gliocladicillins A (1) and B (2). (A) 1 and B (2) inhibited growth of HeLa, HepG2 and MCF-7 tumour cells. Further study demonstrated that both preparations arrested the cell cycle at G2/M phase in a dose-dependent manner, and induced apoptosis through up-regulation of expression of p53, p21, and cyclin B, and activation of caspases-8, -9 and -3. These data imply that gliocladicillins A (1) and B (2) induce tumour cell apoptosis through both extrinsic and intrinsic pathways. In addition, in vivo studies showed that they displayed significant inhibitory effects on cell population growth of melanoma B16 cells imlanted into immunodeficient mice. Conclusions:, Gliocladicillins A (1) and B (2) are effective anti-tumour agents in vitro and in vivo and should be further evaluated for their potential in clinical use. [source] INHIBITION OF TOLL-LIKE RECEPTOR-4, NUCLEAR FACTOR-,B AND MITOGEN-ACTIVATED PROTEIN KINASE BY LIGNOCAINE MAY INVOLVE VOLTAGE-SENSITIVE SODIUM CHANNELSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2008Ping-Ying Lee SUMMARY 1We have shown previously that lignocaine inhibits the upregulation of inducible nitric oxide synthase (iNOS), a crucial factor that initiates the systemic inflammatory response during sepsis, possibly through voltage-sensitive sodium channels (VSSC). Toll-like receptor-4 (TLR-4), nuclear factor (NF)-,B and mitogen activated protein kinases (MAPKs) participate in the upstream regulation of iNOS expression induced by endotoxin. In the present study, we investigated the effects of lignocaine in the regulation of the expression of these enzymes. The role of VSSC in the effects of lignocaine was also investigated. 2Confluent murine macrophages (RAW264.7 cells) were randomized to receive lipopolysaccharide (LPS; 100 ng/mL), LPS + lignocaine (50 µmol/L), LPS + tetrodotoxin (TTX; 1 µmol/L; a VSSC inhibitor), LPS + lignocaine + veratridine (Ver; 50 µmol/L; a VSSC activator) or LPS + TTX + Ver. After reacting with LPS for 0, 15, 30, 45 and 60 min, cell cultures were harvested and enzyme expression was evaluated. 3We found that LPS significantly increased the concentrations of TLR-4, NF-,B and MAPKs, including extracellular regulated kinase (ERK), c-jun N-terminal kinase (JNK) and p38 MAPK, in activated macrophages. Lignocaine and TTX significantly attenuated the effects of LPS on TLR-4, NF-,B, ERK and p38 MAPK expression, but not on JNK. Veratridine mitigated the effects of lignocaine and TTX. 4These data demonstrate that lignocaine has significant inhibitory effects on the activation of TLR-4, NF-,B and MAPKs in activated macrophages. Moreover, these effects involve VSSC. [source] | ||||||||||