Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation
Purpose: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (anti-VEGF) drugs, such as aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. Thi...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Tabriz University of Medical Sciences
2024-07-01
|
| Series: | Advanced Pharmaceutical Bulletin |
| Subjects: | |
| Online Access: | https://apb.tbzmed.ac.ir/PDF/apb-14-469.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849722093637206016 |
|---|---|
| author | Xi Chen Xun Qin Wen Bai Junsong Ren Yang Yu Huiling Nie Xiumiao Li Zhangyu Liu Jiayu Huang Juxue Li Jin Yao Qin Jiang |
| author_facet | Xi Chen Xun Qin Wen Bai Junsong Ren Yang Yu Huiling Nie Xiumiao Li Zhangyu Liu Jiayu Huang Juxue Li Jin Yao Qin Jiang |
| author_sort | Xi Chen |
| collection | DOAJ |
| description | Purpose: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (anti-VEGF) drugs, such as aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV). Methods: Various experiments were conducted to assess the Kavain’s toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a laser-induced CNV mice model. To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed. Results: Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P<0.05). Kavain alleviated CNV in the laser-induced CNV mouse model compared to the control groups (P<0.05). These effects were statistically significantly enhanced in the Kavain plus aflibercept groups (P<0.05). Following Kavain administration, the expression levels of various inflammatory factors were markedly reduced in retinal pigment epithelium (RPE)/choroid complexes (P<0.05). Mechanistically, Kavain decreased the activity of the hypoxia-inducible factor 1α (HIF-1α)/VEGF-A/ VEGF receptor 2 (VEGFR2) signaling pathway. Conclusion: Our study is the first to demonstrate Kavain’s potential as a promising treatment for nAMD, owing to its dual effects of anti-inflammation and anti-angiogenesis. |
| format | Article |
| id | doaj-art-15ca9c6c9bbd4d9da2725c86e942dedf |
| institution | DOAJ |
| issn | 2228-5881 2251-7308 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | Advanced Pharmaceutical Bulletin |
| spelling | doaj-art-15ca9c6c9bbd4d9da2725c86e942dedf2025-08-20T03:11:26ZengTabriz University of Medical SciencesAdvanced Pharmaceutical Bulletin2228-58812251-73082024-07-0114246948210.34172/apb.2024.036apb-42520Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting InflammationXi Chen0Xun Qin1Wen Bai2Junsong Ren3Yang Yu4Huiling Nie5Xiumiao Li6Zhangyu Liu7Jiayu Huang8Juxue Li9Jin Yao10Qin Jiang11The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.Purpose: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (anti-VEGF) drugs, such as aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV). Methods: Various experiments were conducted to assess the Kavain’s toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a laser-induced CNV mice model. To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed. Results: Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P<0.05). Kavain alleviated CNV in the laser-induced CNV mouse model compared to the control groups (P<0.05). These effects were statistically significantly enhanced in the Kavain plus aflibercept groups (P<0.05). Following Kavain administration, the expression levels of various inflammatory factors were markedly reduced in retinal pigment epithelium (RPE)/choroid complexes (P<0.05). Mechanistically, Kavain decreased the activity of the hypoxia-inducible factor 1α (HIF-1α)/VEGF-A/ VEGF receptor 2 (VEGFR2) signaling pathway. Conclusion: Our study is the first to demonstrate Kavain’s potential as a promising treatment for nAMD, owing to its dual effects of anti-inflammation and anti-angiogenesis.https://apb.tbzmed.ac.ir/PDF/apb-14-469.pdfneovascular age-related macular degenerationkavainanti-inflammationanti-angiogenesischoroidal neovascularization |
| spellingShingle | Xi Chen Xun Qin Wen Bai Junsong Ren Yang Yu Huiling Nie Xiumiao Li Zhangyu Liu Jiayu Huang Juxue Li Jin Yao Qin Jiang Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation Advanced Pharmaceutical Bulletin neovascular age-related macular degeneration kavain anti-inflammation anti-angiogenesis choroidal neovascularization |
| title | Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation |
| title_full | Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation |
| title_fullStr | Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation |
| title_full_unstemmed | Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation |
| title_short | Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation |
| title_sort | kavain alleviates choroidal neovascularization via decreasing the activity of the hif 1α vegf a vegfr2 signaling pathway and inhibiting inflammation |
| topic | neovascular age-related macular degeneration kavain anti-inflammation anti-angiogenesis choroidal neovascularization |
| url | https://apb.tbzmed.ac.ir/PDF/apb-14-469.pdf |
| work_keys_str_mv | AT xichen kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT xunqin kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT wenbai kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT junsongren kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT yangyu kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT huilingnie kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT xiumiaoli kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT zhangyuliu kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT jiayuhuang kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT juxueli kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT jinyao kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation AT qinjiang kavainalleviateschoroidalneovascularizationviadecreasingtheactivityofthehif1avegfavegfr2signalingpathwayandinhibitinginflammation |