Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protection
Ischemic stroke (IS) remains a leading cause of disability and mortality worldwide, and inflammation and oxidative stress play significant roles in its pathogenesis. This study investigates the effects of dihydromyricetin (DHM) on IS using RT-qPCR and western blot with SH-SY5Y cells, focusing on its...
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PeerJ Inc.
2024-12-01
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| author | Qi Zeng Yan Xiao Xueliang Zeng Hai Xiao |
| author_facet | Qi Zeng Yan Xiao Xueliang Zeng Hai Xiao |
| author_sort | Qi Zeng |
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| description | Ischemic stroke (IS) remains a leading cause of disability and mortality worldwide, and inflammation and oxidative stress play significant roles in its pathogenesis. This study investigates the effects of dihydromyricetin (DHM) on IS using RT-qPCR and western blot with SH-SY5Y cells, focusing on its effects on the small nucleolar RNA host gene 10 (SNHG10)/microRNA (miR)-665/Ras association domain family member 5 (RASSF5) axis and nuclear factor-kappa B (NF-κB) signaling. In addition, the effects of the SNHG10/miR-665/RASSF5 axis on SH-SY5Y cell activity, apoptosis, oxidative stress, and inflammatory markers were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and enzyme-linked immunosorbent assays. Our results showed that, in response to oxygen-glucose deprivation/reperfusion (OGD/R), DHM treatment improved cell viability, reduced apoptosis, and attenuated neuroinflammation and oxidative stress in a dose-dependent manner (p < 0.05). Interestingly, lncRNA SNHG10 was overexpressed during OGD/R and suppressed by DHM. Through bioinformatics analysis and experimental validation, we identified miR-665 as a direct target of SNHG10 and RASSF5 as a direct target of miR-665. The protective effect of DHM against OGD/R injury was partially reversed by SNHG10 overexpression and further enhanced by co-transfection with the miR-665 mimic and si-RASSF5 (p < 0.05). This study identifies a novel mechanism of DHM against IS, which may act via modulation of the SNHG10/miR-665/RASSF5 axis and inactivation of NF-κB signaling, and offers a promising therapeutic target for IS. |
| format | Article |
| id | doaj-art-bc557f6badbc461689d9bfb02614ae26 |
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| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-bc557f6badbc461689d9bfb02614ae262025-08-20T02:35:18ZengPeerJ Inc.PeerJ2167-83592024-12-0112e1875410.7717/peerj.18754Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protectionQi Zeng0Yan Xiao1Xueliang Zeng2Hai Xiao3Department of Ultrasound, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaDepartment of Cardiovasology, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaDepartment of Pharmacology, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou, ChinaIschemic stroke (IS) remains a leading cause of disability and mortality worldwide, and inflammation and oxidative stress play significant roles in its pathogenesis. This study investigates the effects of dihydromyricetin (DHM) on IS using RT-qPCR and western blot with SH-SY5Y cells, focusing on its effects on the small nucleolar RNA host gene 10 (SNHG10)/microRNA (miR)-665/Ras association domain family member 5 (RASSF5) axis and nuclear factor-kappa B (NF-κB) signaling. In addition, the effects of the SNHG10/miR-665/RASSF5 axis on SH-SY5Y cell activity, apoptosis, oxidative stress, and inflammatory markers were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and enzyme-linked immunosorbent assays. Our results showed that, in response to oxygen-glucose deprivation/reperfusion (OGD/R), DHM treatment improved cell viability, reduced apoptosis, and attenuated neuroinflammation and oxidative stress in a dose-dependent manner (p < 0.05). Interestingly, lncRNA SNHG10 was overexpressed during OGD/R and suppressed by DHM. Through bioinformatics analysis and experimental validation, we identified miR-665 as a direct target of SNHG10 and RASSF5 as a direct target of miR-665. The protective effect of DHM against OGD/R injury was partially reversed by SNHG10 overexpression and further enhanced by co-transfection with the miR-665 mimic and si-RASSF5 (p < 0.05). This study identifies a novel mechanism of DHM against IS, which may act via modulation of the SNHG10/miR-665/RASSF5 axis and inactivation of NF-κB signaling, and offers a promising therapeutic target for IS.https://peerj.com/articles/18754.pdfIschemic strokeDihydromyricetinSNHG10RASSF5miR-665 |
| spellingShingle | Qi Zeng Yan Xiao Xueliang Zeng Hai Xiao Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protection PeerJ Ischemic stroke Dihydromyricetin SNHG10 RASSF5 miR-665 |
| title | Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protection |
| title_full | Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protection |
| title_fullStr | Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protection |
| title_full_unstemmed | Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protection |
| title_short | Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protection |
| title_sort | implications of the snhg10 mir 665 rassf5 nf κb pathway in dihydromyricetin mediated ischemic stroke protection |
| topic | Ischemic stroke Dihydromyricetin SNHG10 RASSF5 miR-665 |
| url | https://peerj.com/articles/18754.pdf |
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