ReferenceID 2788
Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal
J Neuroinflammation
BACKGROUND: Upregulation of matrix metalloproteinase-9 (MMP-9) has been indicated as one of the inflammatory biomarkers. In the central nervous system (CNS), the MMP-9 is induced by several proinflammatory mediators and
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- Reference Id
- 2788
- Evidence Id
- 19378
- Core Evidence Id
- 19378
- Source Reference Id
- 5580
- Herb2 Reference Id
- HBREF006377
- Subject Paper Key
- HBIN042467_32505192
- Pubmed Id
- 32505192
- Doi
- 10.1186/s12974-020-01859-5
- Paper Title
- Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal
- Paper Abstract
- BACKGROUND: Upregulation of matrix metalloproteinase-9 (MMP-9) has been indicated as one of the inflammatory biomarkers. In the central nervous system (CNS), the MMP-9 is induced by several proinflammatory mediators and participates in the CNS disorders, including inflammation and neurodegeneration. In addition, protein kinase Cs (PKCs) has been shown to be involved in regulation of various inflammatory factors like MMP-9 by several stimuli in many cell types. Several phytochemicals are believed to reduce the risk of several inflammatory disorders including the CNS diseases. The rottlerin, a principal phenolic compound of the Kamala plant Mallotus philippinensis, has been shown to possess an array of medicinal properties, including anti-PKC-delta, antitumor, anti-oxidative, and anti-inflammatory activities. METHODS: Herein, we used rat brain astrocytes (RBA) to demonstrate the signaling mechanisms of phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression by zymographic, RT-PCR, subcellular isolation, Western blot, ROS detection, and promoter reporter analyses. Then, we evaluate the effects of rottlerin on PMA-induced MMP-9 expression in RBA and its influencing mechanism. RESULTS: We first demonstrated that PMA stimulated activation of various types of PKC, including PKC-delta in RBA. Subsequently, PMA induced MMP-9 expression via PKCdelta-mediated reactive oxygen species (ROS) generation, extracellular signal-regulated kinase 1/2 (ERK1/2) activation, and then induced c-Fos/AP-1 signaling pathway. Finally, upregulation of MMP-9 by PMA via the pathway may promote astrocytic migration, and the event could be attenuated by rottlerin. CONCLUSIONS: These data indicated that rottlerin may have anti-inflammatory activity by reducing these related pathways of PKC-delta-dependent ROS-mediated MMP-9 expression in brain astrocytes.
- Journal
- J Neuroinflammation
- Publish Year
- 2020
- Experiment Subject
- rat
- Experiment Type
- Cell Experiment
- Phenotype Related
- Neurodegeneration; Inflammation; Cns Diseases; Cns Disorders; Inflammatory Disorders
- Paper Title Cn
- Paper Title En
- Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal
- Bilingual Status
- semi_complete