A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic Migration
Matrix metalloproteinases (MMPs), which are proteolytic enzymes, promote blood–brain barrier (BBB) disruption, leading to neuronal damage and neuroinflammation. Among them, MMP-9 upregulation serves as an inflammatory biomarker in the central nervous system (CNS). Currently, the development of marin...
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MDPI AG
2024-01-01
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| author | Tsong-Hai Lee Jiun-Liang Chen Chuan-Hsin Chang Ming-Ming Tsai Hui-Ching Tseng Yu-Chia Chang Velayuthaprabhu Shanmugam Hsi-Lung Hsieh |
| author_facet | Tsong-Hai Lee Jiun-Liang Chen Chuan-Hsin Chang Ming-Ming Tsai Hui-Ching Tseng Yu-Chia Chang Velayuthaprabhu Shanmugam Hsi-Lung Hsieh |
| author_sort | Tsong-Hai Lee |
| collection | DOAJ |
| description | Matrix metalloproteinases (MMPs), which are proteolytic enzymes, promote blood–brain barrier (BBB) disruption, leading to neuronal damage and neuroinflammation. Among them, MMP-9 upregulation serves as an inflammatory biomarker in the central nervous system (CNS). Currently, the development of marine organism-derived bioactive compounds or metabolites as anti-inflammatory drugs has received considerable attention. The 9,11-secosteroid, 3β,11-dihydroxy-9,11-secogorgost-5-en-9-one (4p3f), is a novel sterol compound extracted from the soft coral <i>Sinularia leptoclado</i> with potential anti-inflammatory activity. However, the effect of and potential for brain protection of 4p3f on brain astrocytes remain unclear. Herein, we used rat brain astrocytes (RBAs) to investigate the effects and signaling mechanisms of 4p3f on lipopolysaccharide (LPS)-induced MMP-9 expression via zymographic, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), Western blot, immunofluorescence staining, promoter–reporter, and cell migration analyses. We first found that 4p3f blocked LPS-induced MMP-9 expression in RBAs. Next, we demonstrated that LPS induced MMP-9 expression via the activation of ERK1/2, p38 MAPK, and JNK1/2, which is linked to the STAT3-mediated NF-κB signaling pathway. Finally, 4p3f effectively inhibited LPS-induced upregulation of MMP-9-triggered RBA cell migration. These data suggest that a novel sterol from soft coral, 4p3f, may have anti-inflammatory and brain-protective effects by attenuating these signaling pathways of MMP-9-mediated events in brain astrocytes. Accordingly, the soft coral-derived sterol 4p3f may emerge as a potential candidate for drug development or as a natural compound with neuroprotective properties. |
| first_indexed | 2024-03-08T09:57:13Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-08T09:57:13Z |
| publishDate | 2024-01-01 |
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| spelling | doaj.art-c86918f515ad4af184d9f15b45eb9dfc2024-01-29T13:47:58ZengMDPI AGBiomedicines2227-90592024-01-0112122610.3390/biomedicines12010226A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic MigrationTsong-Hai Lee0Jiun-Liang Chen1Chuan-Hsin Chang2Ming-Ming Tsai3Hui-Ching Tseng4Yu-Chia Chang5Velayuthaprabhu Shanmugam6Hsi-Lung Hsieh7Stroke Center and Stroke Section, Department of Neurology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanDivision of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanDivision of Basic Medical Sciences, Department of Nursing, Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, TaiwanDivision of Basic Medical Sciences, Department of Nursing, Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, TaiwanDivision of Basic Medical Sciences, Department of Nursing, Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, TaiwanDivision of Basic Medical Sciences, Department of Nursing, Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, TaiwanDepartment of Biotechnology, Bharathiar University, Coimbatore 641046, IndiaDivision of Basic Medical Sciences, Department of Nursing, Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, TaiwanMatrix metalloproteinases (MMPs), which are proteolytic enzymes, promote blood–brain barrier (BBB) disruption, leading to neuronal damage and neuroinflammation. Among them, MMP-9 upregulation serves as an inflammatory biomarker in the central nervous system (CNS). Currently, the development of marine organism-derived bioactive compounds or metabolites as anti-inflammatory drugs has received considerable attention. The 9,11-secosteroid, 3β,11-dihydroxy-9,11-secogorgost-5-en-9-one (4p3f), is a novel sterol compound extracted from the soft coral <i>Sinularia leptoclado</i> with potential anti-inflammatory activity. However, the effect of and potential for brain protection of 4p3f on brain astrocytes remain unclear. Herein, we used rat brain astrocytes (RBAs) to investigate the effects and signaling mechanisms of 4p3f on lipopolysaccharide (LPS)-induced MMP-9 expression via zymographic, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), Western blot, immunofluorescence staining, promoter–reporter, and cell migration analyses. We first found that 4p3f blocked LPS-induced MMP-9 expression in RBAs. Next, we demonstrated that LPS induced MMP-9 expression via the activation of ERK1/2, p38 MAPK, and JNK1/2, which is linked to the STAT3-mediated NF-κB signaling pathway. Finally, 4p3f effectively inhibited LPS-induced upregulation of MMP-9-triggered RBA cell migration. These data suggest that a novel sterol from soft coral, 4p3f, may have anti-inflammatory and brain-protective effects by attenuating these signaling pathways of MMP-9-mediated events in brain astrocytes. Accordingly, the soft coral-derived sterol 4p3f may emerge as a potential candidate for drug development or as a natural compound with neuroprotective properties.https://www.mdpi.com/2227-9059/12/1/226soft corallipopolysaccharidematrix metalloproteinase-9cell migrationbrain astrocytesanti-inflammation |
| spellingShingle | Tsong-Hai Lee Jiun-Liang Chen Chuan-Hsin Chang Ming-Ming Tsai Hui-Ching Tseng Yu-Chia Chang Velayuthaprabhu Shanmugam Hsi-Lung Hsieh A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic Migration Biomedicines soft coral lipopolysaccharide matrix metalloproteinase-9 cell migration brain astrocytes anti-inflammation |
| title | A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic Migration |
| title_full | A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic Migration |
| title_fullStr | A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic Migration |
| title_full_unstemmed | A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic Migration |
| title_short | A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic Migration |
| title_sort | brain protective sterol from soft coral inhibits lipopolysaccharide induced matrix metalloproteinase 9 mediated astrocytic migration |
| topic | soft coral lipopolysaccharide matrix metalloproteinase-9 cell migration brain astrocytes anti-inflammation |
| url | https://www.mdpi.com/2227-9059/12/1/226 |
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