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Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal.
Metadata
Journaljournal of neuroinflammation5.793Date
2020 Jun 06
5 months ago
Type
Journal Article
Volume
2020-Jun-06 / 17 : 177
Author
Lee TH 1, Chen JL 2, Liu PS 3, Tsai MM 4, 5, Wang SJ 6, Hsieh HL 7, 8
Affiliation
  • 2. Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • 3. Department of Microbiology, Soochow University, Taipei, Taiwan.
  • 4. Department of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, 261 Wenhua 1st Road, Guishan, Taoyuan, Taiwan.
  • 5. Department of General Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
  • 6. School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
  • 7. Department of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, 261 Wenhua 1st Road, Guishan, Taoyuan, Taiwan. [email protected]
  • 8. Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. [email protected]
Doi
PMIDMESH
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-δ, 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-δ in RBA. Subsequently, PMA induced MMP-9 expression via PKCδ-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-δ-dependent ROS-mediated MMP-9 expression in brain astrocytes.
Keywords: Brain astrocytes Matrix metalloproteinase-9 Neuroinflammation Protein kinase C-δ Reactive oxygen species Rottlerin
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5.8
J Neuroinflammationjournal of neuroinflammation
Metadata
LocationEngland
FromBMC

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