Rhamnetin Prevents Bradykinin-Induced Expression of Matrix Metalloproteinase-9 in Rat Brain Astrocytes by Suppressing Protein Kinase-Dependent AP-1 Activation
Bradykinin (BK) has been recognized as a stimulant for matrix metalloproteinase (MMP)-9 expression, contributing to neuroinflammation. Modulating the BK/MMP-9 pathway offers potential in the treatment of neuroinflammatory disorders. Rhamnetin (RNT), a flavonoid compound known for its antioxidant and...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/12/3198 |
| _version_ | 1797381941340667904 |
|---|---|
| author | Chuen-Mao Yang I-Ta Lee Li-Der Hsiao Zih-Yao Yu Chien-Chung Yang |
| author_facet | Chuen-Mao Yang I-Ta Lee Li-Der Hsiao Zih-Yao Yu Chien-Chung Yang |
| author_sort | Chuen-Mao Yang |
| collection | DOAJ |
| description | Bradykinin (BK) has been recognized as a stimulant for matrix metalloproteinase (MMP)-9 expression, contributing to neuroinflammation. Modulating the BK/MMP-9 pathway offers potential in the treatment of neuroinflammatory disorders. Rhamnetin (RNT), a flavonoid compound known for its antioxidant and anti-inflammatory effects, has shown promise. However, the specific mechanisms through which RNT inhibits BK-induced MMP-9 expression remain unclear. Therefore, this study aims to delve into the intricate mechanisms underlying this process. Here, we initially demonstrated that RNT effectively attenuated BK-induced MMP-9 expression and its associated cell migration in rat brain astrocyte-1 (RBA-1) cells. Further investigation revealed that BK-driven MMP-9 protein, mRNA, and promoter activity linked to cell migration relied on c-Src, Pyk2, EGFR, PDGFR, PI3K/Akt, JNK1/2, and c-Jun. This was validated by the inhibition of these effects through specific inhibitors, a finding substantiated by the introduction of siRNAs targeting these signaling molecules. Notably, the phosphorylated levels of these signaling components induced by BK were significantly reduced by their respective inhibitors and RNT, underscoring the inhibitory role of RNT in this process. These findings indicate that, in RBA-1 cells, RNT diminishes the heightened induction of MMP-9 triggered by BK through the inhibition of c-Src/Pyk2/PDGFR and EGFR/PI3K/Akt/JNK1/2-dependent AP-1 activation. This suggests that RNT holds promise as a potential therapeutic approach for addressing neuroinflammation in the brain. |
| first_indexed | 2024-03-08T20:58:19Z |
| format | Article |
| id | doaj.art-05cb1b020fbc4db58b39a1d215b9f181 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-08T20:58:19Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-05cb1b020fbc4db58b39a1d215b9f1812023-12-22T13:54:56ZengMDPI AGBiomedicines2227-90592023-12-011112319810.3390/biomedicines11123198Rhamnetin Prevents Bradykinin-Induced Expression of Matrix Metalloproteinase-9 in Rat Brain Astrocytes by Suppressing Protein Kinase-Dependent AP-1 ActivationChuen-Mao Yang0I-Ta Lee1Li-Der Hsiao2Zih-Yao Yu3Chien-Chung Yang4Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242062, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110301, TaiwanGraduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242062, TaiwanGraduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242062, TaiwanDepartment of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Taoyuan, Taoyuan 333008, TaiwanBradykinin (BK) has been recognized as a stimulant for matrix metalloproteinase (MMP)-9 expression, contributing to neuroinflammation. Modulating the BK/MMP-9 pathway offers potential in the treatment of neuroinflammatory disorders. Rhamnetin (RNT), a flavonoid compound known for its antioxidant and anti-inflammatory effects, has shown promise. However, the specific mechanisms through which RNT inhibits BK-induced MMP-9 expression remain unclear. Therefore, this study aims to delve into the intricate mechanisms underlying this process. Here, we initially demonstrated that RNT effectively attenuated BK-induced MMP-9 expression and its associated cell migration in rat brain astrocyte-1 (RBA-1) cells. Further investigation revealed that BK-driven MMP-9 protein, mRNA, and promoter activity linked to cell migration relied on c-Src, Pyk2, EGFR, PDGFR, PI3K/Akt, JNK1/2, and c-Jun. This was validated by the inhibition of these effects through specific inhibitors, a finding substantiated by the introduction of siRNAs targeting these signaling molecules. Notably, the phosphorylated levels of these signaling components induced by BK were significantly reduced by their respective inhibitors and RNT, underscoring the inhibitory role of RNT in this process. These findings indicate that, in RBA-1 cells, RNT diminishes the heightened induction of MMP-9 triggered by BK through the inhibition of c-Src/Pyk2/PDGFR and EGFR/PI3K/Akt/JNK1/2-dependent AP-1 activation. This suggests that RNT holds promise as a potential therapeutic approach for addressing neuroinflammation in the brain.https://www.mdpi.com/2227-9059/11/12/3198neuroinflammationrhamnetinbradykininprotein tyrosine kinasesmatrix metalloproteinase-9astrocytes |
| spellingShingle | Chuen-Mao Yang I-Ta Lee Li-Der Hsiao Zih-Yao Yu Chien-Chung Yang Rhamnetin Prevents Bradykinin-Induced Expression of Matrix Metalloproteinase-9 in Rat Brain Astrocytes by Suppressing Protein Kinase-Dependent AP-1 Activation Biomedicines neuroinflammation rhamnetin bradykinin protein tyrosine kinases matrix metalloproteinase-9 astrocytes |
| title | Rhamnetin Prevents Bradykinin-Induced Expression of Matrix Metalloproteinase-9 in Rat Brain Astrocytes by Suppressing Protein Kinase-Dependent AP-1 Activation |
| title_full | Rhamnetin Prevents Bradykinin-Induced Expression of Matrix Metalloproteinase-9 in Rat Brain Astrocytes by Suppressing Protein Kinase-Dependent AP-1 Activation |
| title_fullStr | Rhamnetin Prevents Bradykinin-Induced Expression of Matrix Metalloproteinase-9 in Rat Brain Astrocytes by Suppressing Protein Kinase-Dependent AP-1 Activation |
| title_full_unstemmed | Rhamnetin Prevents Bradykinin-Induced Expression of Matrix Metalloproteinase-9 in Rat Brain Astrocytes by Suppressing Protein Kinase-Dependent AP-1 Activation |
| title_short | Rhamnetin Prevents Bradykinin-Induced Expression of Matrix Metalloproteinase-9 in Rat Brain Astrocytes by Suppressing Protein Kinase-Dependent AP-1 Activation |
| title_sort | rhamnetin prevents bradykinin induced expression of matrix metalloproteinase 9 in rat brain astrocytes by suppressing protein kinase dependent ap 1 activation |
| topic | neuroinflammation rhamnetin bradykinin protein tyrosine kinases matrix metalloproteinase-9 astrocytes |
| url | https://www.mdpi.com/2227-9059/11/12/3198 |
| work_keys_str_mv | AT chuenmaoyang rhamnetinpreventsbradykinininducedexpressionofmatrixmetalloproteinase9inratbrainastrocytesbysuppressingproteinkinasedependentap1activation AT italee rhamnetinpreventsbradykinininducedexpressionofmatrixmetalloproteinase9inratbrainastrocytesbysuppressingproteinkinasedependentap1activation AT liderhsiao rhamnetinpreventsbradykinininducedexpressionofmatrixmetalloproteinase9inratbrainastrocytesbysuppressingproteinkinasedependentap1activation AT zihyaoyu rhamnetinpreventsbradykinininducedexpressionofmatrixmetalloproteinase9inratbrainastrocytesbysuppressingproteinkinasedependentap1activation AT chienchungyang rhamnetinpreventsbradykinininducedexpressionofmatrixmetalloproteinase9inratbrainastrocytesbysuppressingproteinkinasedependentap1activation |