Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation.

Autor: Chen, Xi, Qin, Xun, Bai, Wen, Ren, Junsong, Yu, Yang, Nie, Huiling, Li, Xiumiao, Liu, Zhangyu, Huang, Jiayu, Li, Juxue, Yao, Jin, Jiang, Qin
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Zdroj: Advanced Pharmaceutical Bulletin; 2024, Vol. 14 Issue 2, p469-482, 14p
Abstrakt: 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).>P<0.05).>PP 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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