ABSTRACT
Triptolide has been widely reported to exhibit potential therapeutic value in multiple inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. Although its safety and efficacy as an anti-inflammatory agent have been verified by many studies, the effect of triptolide on osteoarthritis (OA) was not clearly understood. In this study, we found that triptolide prevented OA development in a surgical destabilization of the medial meniscus (DMM) mouse model. In addition, triptolide inhibited both DMM-induced and LPS-induced expression of pro-inflammatory cytokines in the human monocytic cell line THP-1. Further mechanistic studies showed that the reduction of pro-inflammatory cytokines by triptolide was mediated by the upregulation of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) and downregulation of caspase-1. Finally, we identified that hsa-miR-20b, a microRNA targeting the NLRP3 gene, was downregulated by triptolide. This study provides a novel insight into the effect on triptolide in preventing OA pathogenesis.
Subject(s)
Diterpenes/pharmacology , MicroRNAs/genetics , Osteoarthritis/genetics , Osteoarthritis/prevention & control , Phenanthrenes/pharmacology , Animals , Cell Line , Cytokines/genetics , Disease Models, Animal , Down-Regulation/drug effects , Down-Regulation/genetics , Epoxy Compounds/pharmacology , Humans , Male , Mice , Mice, Inbred C57BL , Monocytes/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , THP-1 Cells , Up-Regulation/drug effects , Up-Regulation/geneticsABSTRACT
RATIONALE: Phenolic compounds are commonly found in fossel fuels and bio-oils, and have a detrimental effect on the chemical stability of the fuels. A selective analytical method is needed to characterize the phenolic compounds in complex hydrocarbon mixtures. METHODS: Gas chromatography/atmospheric pressure chemical ionization mass spectrometry (GC/APCI-MS) was used to characterize the phenolic compounds in a low-temperature coal tar and its narrow distillate fractions. RESULTS: Negative-ion APCI selectively ionized phenolic compounds in the coal tar. The [M-H](-) and [M-H + O](-) ions were derived from monohydric phenols, while [M-H](-) , [M-2H](-) , and [M-2H + O](-) were from benzenediols. Monohydric phenolic compounds with 1-4 aromatic rings and some dihydric phenolic compounds were identified. The results from GC/APCI-MS were validated by those from negative electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FTICRMS). CONCLUSIONS: Negative-ion GC/APCI-MS was proposed and successfully used to characterize phenolic compounds in coal tar samples. This technique can potentially be used for the characterization of phenolic compounds in other complex hydrocarbon systems. Copyright © 2016 John Wiley & Sons, Ltd.
ABSTRACT
Tanshinone IIA (TSA) is a lipophilic diterpene purified from the Chinese herb Danshen, which exhibits potent antioxidant and anti-inflammatory properties. Effect of TSA remains largely uninvestigated on the osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs), which are widely used in cell-based therapy of bone diseases. In the present study, both ALP activity at day 7 and calcium content at day 24 were upregulated during the osteogenesis of mouse BM-MSCs treated with TSA (1 and 5 µM), demonstrating that it promoted the osteogenesis at both early and late stages. We found that TSA promoted osteogenesis and inhibited osteoclastogenesis, evident by RT-PCR analysis of osteogenic marker gene expressions. However, osteogenesis was inhibited by TSA at 20 µM. We further revealed that TSA (1 and 5 µM) upregulated BMP and Wnt signaling. Co-treatment with Wnt inhibitor DKK-1 or BMP inhibitor noggin significantly decreased the TSA-promoted osteogenesis, indicating that upregulation of BMP and Wnt signaling plays a significant role and contributes to the TSA-promoted osteogenesis. Of clinical interest, our study suggests TSA as a promising therapeutic strategy during implantation of BM-MSCs for a more effective treatment of bone diseases.
Subject(s)
Abietanes/pharmacology , Mesenchymal Stem Cells/drug effects , Osteoblasts/drug effects , Osteogenesis/drug effects , Alkaline Phosphatase/metabolism , Animals , Bone Morphogenetic Proteins/metabolism , Calcium/metabolism , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Gene Expression Regulation/drug effects , Mesenchymal Stem Cells/cytology , Mice, Inbred BALB C , Osteoblasts/cytology , Osteogenesis/genetics , Osteogenesis/physiology , Wnt Signaling Pathway/drug effectsABSTRACT
The electrogenerated chemiluminescence (ECL) behavior of N-(4-aminobutyl)-N-ethylisoluminol (ABEI) was studied and it was found that ABEI could produce emission light when oxidized at a +1.0 V (vs. Ag/AgCl) potential in alkaline solution. The addition of H2O2 markedly improved the ECL sensitivity. The pH value of the solution as well as the H2O2 concentration and working potential all have influences on the ECL response. Under optimal conditions, ABEI can be detected in the range 1.3 x 10(-6)-6.5 x 10(-12) mol L(-1). A detection limit of 2.2 x 10(-12) mol L(-1) for ABEI was obtained at a signal-to-noise ratio of 3. ABEI was then used as a marker to label a known sequence oligonucleotide, which was used as a DNA probe for identifying a target ssDNA immobilized on a PPy modified electrode based on a specific hybridization reaction. The hybridization events were evaluated by the ECL measurements. The results showed that only a complementary sequence could form a double-stranded DNA with the DNA probe and give a strong ECL response. A three-base mismatch sequence and non-complementary sequence have no response. The intensity of the ECL was linearly related to the concentration of the complementary sequence in the range 9.6 x 10(-11)-9.6 x 10(-8) mol L(-1), the detection limit was 3.0 x 10(-11) mol L(-1).
