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1.
Abnormal aggregation of amyloid-β (Aβ) peptides and associated inflammation and apoptosis in cerebrovascular endothelial cells are prelude to inhibition of onset of vascular dementia (VaD). Although small molecules have been widely used to mitigate the cell damage induced by aggregated species of Aβ, its molecular mechanism based on anti-amyloid properties and corresponding mitigation of cytotoxicity against cerebrovascular endothelial cells have not been elucidated. Herein, we used cryptotanshinone as the major bioactive compound from the root of Salvia miltiorrhiza Bunge to effectively inhibit Aβ fibrillation and associated cytotoxicity. Thoflavin T (ThT) and 1-Anilino-8-naphthalene sulfonate (ANS) fluorescence, Congo red, and circular dichroism (CD) analyses indicted that cryptotanshinone potentially inhibit Aβ1-42 aggregation through elongation of nucleation phase, apparent decrease in the slope of the growth phase, and the final fluorescence intensity in a concentration-dependent manner. Also, cell viability, inflammation and capsae-3 assays showed that co-incubation of Aβ1-42 peptide with cryptotanshinone in the aggregation buffer not only mitigated their cytotoxicity, but also reduced the levels of TNF-α, IL-1β, IL-6 and caspase-3 activity in cerebrovascular endothelial cells induced by Aβ1-42. This study suggested that cryptotanshinone may show a great promise in the development of small molecule-based platforms for the treatment of VaD.  相似文献   

2.
He X  Shu J  Xu L  Lu C  Lu A 《Molecules (Basel, Switzerland)》2012,17(3):3155-3164
Astragalus polysaccharides (APS), one of main bioactive components in Astragalus membranaceus Bunge, has been reported to possess anti-inflammatory activities, but the molecular mechanisms behind this activity are largely unknown. This study aimed to investigate expression of inflammatory cytokines and the MAPK/NF-κB pathway in human THP-1 macrophages induced by lipopolysaccharide (LPS). The results showed that the concentrations of TNF-a and IL-1β released from LPS stimulated THP-1 cells increased significantly compared to control (p < 0.01). After treatment with APS, the TNF-a and IL-1β levels were significantly lower than those in the LPS group (p < 0.05). The mRNA expression of TNF-a and IL-1β were also inhibited. Mechanistic studies indicated that APS strongly suppressed NF-κB activation and down-regulated the phosphorylation of ERK and JNK, which are important signaling pathways involved in the production of TNF-a and IL-1β, demonstrating that APS could suppress the production of TNF-a and IL-1β by LPS stimulated macrophages by inhibiting NF-κB activation and ERK and JNK phosphorylation.  相似文献   

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BackgroundAllergic asthma is a inflammatory disease defined as a condition of chronic airway inflammation. Asthma can be provoked by various stimuli like allergens inhalation like dust particles, pollen, and pollutants in the air.ObjectiveThis exploration was dedicated to investigate the anti-asthmatic properties of tilianin against the ovalbumin (OVA)-initiated asthma in mice.MethodologyThe asthma was provoked to the mice via administering 100 μl of aluminum hydroxide containing 20 μg of OVA and treated with the 10 and 20 mg/kg of tilianin, respectively. The levels of Th2 cytokines, OVA-specific IgE, eotaxin, pro-inflammatory mediators, antioxidants, and other markers were inspected by marker specific assay kits. The mRNA expressions of TGF-β1, Smad, iNOS, and COX-2 was assessed using RT-PCR analysis. The lung histology was analyzed microscopically to detect the histological changes.ResultsTilianin treatment remarkably suppressed the IL-4, IL-5, and IL-13, IFN-γ, eotaxin, and IgE levels. The NO, MPO, and inflammatory makers TNF-α, IL-6, IL-12, and TXB2 was substantially diminished by the tilianin treatment. The TGF-β1, iNOS, and COX-2 expressions were appreciably suppressed by the tilianin. The histological findings proved that the tilianin treatment alleviated the OVA-provoked histopathological changes in the lung tissues.ConclusionOur findings proved that tilianin effectively alleviated the OVA-provoked asthma in animals and it could be a talented anti-asthmatic candidate.  相似文献   

5.
Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis™, we identified genes (up- or down-regulated, ≥ 1.5 fold, P ≤ 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 µg/ml) in UtLM cells. Downregulation of TGF-β signaling pathway genes, activin A, activin B, Smad3, TGF-β2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that down-regulation of activin A and Smad3, both members of the TGF-β pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.  相似文献   

6.
This study aims to explore and evaluate the effects of Semen Ziziphi Spinosae extracts on the serum levels of interleukin (IL)-6, IFN-γ, IL-1β, TNF-α, IL-10 and IL-4 in mice, and the regulative effect of Semen Ziziphi Spinosae on the cytokine system. Using an ELISA assay, the serum levels of IL-6, IFN-γ, IL-1β, TNF-α, IL-10 and IL-4 were examined in mice after intraperitoneal injection (i.p.) with Semen Ziziphi Spinosae extracts. The results showed that the levels of IL-6 and IL-1β were significantly increased compared with the control groups (p<0.01), while the level of tumour necrosis factor-α (TNF-α) was significantly decreased (p<0.01). Semen Ziziphi Spinosae possesses certain modulation effects on cytokines, and the immuno-regulating function and hypnosis effects of Semen Ziziphi Spinosae may be relevant to these modulation effects on cytokines.  相似文献   

7.
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. Transforming growth factor-β1 (TGF-β1) is a secreted protein that promotes differentiation of synovial fibroblasts to α-smooth muscle actin (α-SMA)-positive myofibroblasts to repair the damaged joints. Synovial fluid from patients with RA (RA-SF) induced expression of α-SMA in human adipose tissue-derived mesenchymal stem cells (hASCs). RA-SF-induced α-SMA expression was abrogated by immunodepletion of TGF-β1 from RA-SF with anti-TGF-β1 antibody. Furthermore, pretreatment of hASCs with the TGF-β type I receptor inhibitor SB431542 or lentiviral small hairpin RNA-mediated silencing of TGF-β type I receptor expression in hASCs blocked RA-SF-induced α-SMA expression. Small interfering RNA-mediated silencing of Smad2 or adenoviral overexpression of Smad7 (an inhibitory Smad isoform) completely inhibited RA-SF-stimulated α-SMA expression. These results suggest that TGF-β1 plays a pivotal role in RA-SF-induced differentiation of hASCs to α-SMA-positive cells.  相似文献   

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