|The protective effect of tetramethylpyrazine on cartilage explants and chondrocytes|
|Ju, Xiao-dong1; Deng, Min2; Ao, Ying-fang1; Yu, Chang-long1; Wang, Jian-quan1; Yu, Jia-kuo1; Cui, Guo-qing1; Hu, Yue-lin1|
|关键词||Tetramethylpyrazine Cartilage Chondrocyte Apoptosis Metalloproteinases-3 Tissue Inhibitors Of Metalloproteinase-1|
|刊名||JOURNAL OF ETHNOPHARMACOLOGY|
|WOS标题词||Science & Technology|
|类目[WOS]||Plant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy|
|研究领域[WOS]||Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine|
|关键词[WOS]||GENE-EXPRESSION ; OSTEOARTHRITIC CARTILAGE ; LIGUSTICUM-CHUANXIONG ; ARTICULAR-CARTILAGE ; N-ACETYLCYSTEINE ; IN-VITRO ; INTERLEUKIN-1-BETA ; DEGRADATION ; APOPTOSIS ; DAMAGE|
Aims of study: Ligusticum wallichi Franchat (chuanxiong) is a very common traditional Chinese herbal medicine in China. Tetramethylpyrazine (IMP) is a major active ingredient extracted from Ligusticum wallichi Franchat. We investigated the protective effect of IMP on interleukin-1 beta (IL-1 beta) induced proteoglycan (PG) degradation and apoptosis in rabbit articular cartilage and chondrocytes.
Materials and methods: Rabbit articular cartilage explants and chondrocytes were cultured with 10 ng/ml IL-1 beta for 72 h in the absence or presence of various concentrations of TMP (50, 100 or 200 mu M). Cartilage and chondroprotective effects of IMP were determined by evaluating (1) the degree of PG degradation by measuring the amount of glycosaminoglycan (GAG) released into the culture media with 1,9-dimethylmethylene blue (DMMB) assay in cartilage explants; (2) gene expression of MMP-3 and TIMP-1 by real-time quantitative reverse transcription-polymerase chain reaction analysis in cartilage explants; (3) chondrocytes viability with MTT assay; (4) the production of intracellular reactive oxygen species (ROS) with laser scanning confocal microscopy (LSCM). Anti-apoptotic effects of TMP were determined by measuring (1) apoptosis with flow cytometric analysis; (2) mitochondrial membrane potential assay with LSCM; (3) caspase-3 activity with special assay kit.
Results: IL-1 beta treatment increased the level of GAG released into the culture media, and induced the gene expression of MMP-3 and inhibited the gene expression of TIMP-1 in cartilage explants. Moreover, IL-1 beta treatment decreased the cell viability and mitochondrial membrane potential, and enhanced the level of intracellular ROS, apoptosis rate, and caspase-3 activity in chondrocytes. However, simultaneous treatment with TMP attenuated the IL-1 beta-induced cartilage and chondrocyte destruction in a dose-dependent manner. IMP showed the decrease of GAG degradation and MMP-3 mRNA production, and the enhancement of TIMP-1 mRNA production in cartilage explants. TMP also increased the cell viability in chondrocytes. Furthermore, TMP inhibited the chondrocytes apoptosis through suppression of ROS production, maintaining of mitochondrial membrane potential and downregulation of caspase-3 activity.
Conclusion: These results demonstrate that IMP has the cartilage and chondroprotective effect, which suggest that TMP could act as an agent for pharmacological intervention in the progress of OA. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
|项目编号||30973043 ; 30700906 ; 7102159 ; 2007A008|
|资助机构||National Natural Science Foundation of China ; Beijing Municipal Natural Science Foundation ; Science and Technology New Star Funds of Beijing|
|作者单位||1.Peking Univ, Hosp 3, Inst Sports Med, Beijing 100191, Peoples R China|
2.Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China
|Ju, Xiao-dong,Deng, Min,Ao, Ying-fang,et al. The protective effect of tetramethylpyrazine on cartilage explants and chondrocytes[J]. JOURNAL OF ETHNOPHARMACOLOGY,2010,132(2):414-420.|
|APA||Ju, Xiao-dong.,Deng, Min.,Ao, Ying-fang.,Yu, Chang-long.,Wang, Jian-quan.,...&Hu, Yue-lin.(2010).The protective effect of tetramethylpyrazine on cartilage explants and chondrocytes.JOURNAL OF ETHNOPHARMACOLOGY,132(2),414-420.|
|MLA||Ju, Xiao-dong,et al."The protective effect of tetramethylpyrazine on cartilage explants and chondrocytes".JOURNAL OF ETHNOPHARMACOLOGY 132.2(2010):414-420.|