School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
Eur J Pharmacol. 2024 Oct 15;981:176883. doi: 10.1016/j.ejphar.2024.176883. Epub 2024 Aug 10.
Glaucine is an aporphine alkaloid with anti-inflammatory, bronchodilator and anti-cancer activities. However, the effects of glaucine in the regulation of age-related macular degeneration (AMD) remain unclear. Herein, we aimed to investigate the anti-angiogenetic and anti-inflammatory effects of glaucine in ARPE-19 cells. ARPE-19 cells were treated with N-(methoxyoxoacetyl)-glycine, methyl ester (DMOG) and cobalt chloride (CoCl) for induction of hypoxia, while lipopolysaccharide (LPS) treatment was used for elicitation of inflammatory response. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by Western blot. The secretion of VEGF, interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) was detected using enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were used for tube formation analysis. Expression of HIF-1α and secretion of VEGF were significantly increased under DMOG and CoCl induction, whereas glaucine significantly attenuated both HIF-1α expression and VEGF secretion by DMOG- and CoCl-induced ARPE-19 cells. In addition, glaucine suppressed the tube formation by DMOG- and CoCl-induced HUVEC cells. Moreover, glaucine also attenuated the production of IL-6 and MCP-1 by LPS-induced ARPE-19 cells. This study indicated that glaucine exhibited anti-angiogenic and anti-inflammatory effects, suggesting that glaucine might have benefits for the treatment of AMD.
格尔吉辛是一种阿朴啡类生物碱，具有抗炎、支气管扩张和抗癌作用。然而，格尔吉辛在调节年龄相关性黄斑变性（AMD）中的作用尚不清楚。在此，我们旨在研究格尔吉辛在 ARPE-19 细胞中抗血管生成和抗炎的作用。用 N-（甲氧基氧代乙酰基）-甘氨酸甲酯（DMOG）和氯化钴（CoCl）处理 ARPE-19 细胞诱导缺氧，用脂多糖（LPS）处理引发炎症反应。用 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）法分析细胞活力。用 Western blot 法测定缺氧诱导因子（HIF-1α）和血管内皮生长因子（VEGF）的表达。用酶联免疫吸附试验（ELISA）检测 VEGF、白细胞介素（IL）-6 和单核细胞趋化蛋白-1（MCP-1）的分泌。用人脐静脉内皮细胞（HUVEC）进行管形成分析。DMOG 和 CoCl 诱导后，HIF-1α 表达和 VEGF 分泌明显增加，而格尔吉辛显著减弱了 DMOG 和 CoCl 诱导的 ARPE-19 细胞中 HIF-1α 表达和 VEGF 分泌。此外，格尔吉辛还抑制了 DMOG 和 CoCl 诱导的 HUVEC 细胞的管形成。此外，格尔吉辛还减弱了 LPS 诱导的 ARPE-19 细胞中 IL-6 和 MCP-1 的产生。本研究表明，格尔吉辛具有抗血管生成和抗炎作用，提示格尔吉辛可能有益于 AMD 的治疗。
