Al-Eitan Laith, Abusirdaneh Rawan
Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan.
J Taibah Univ Med Sci. 2024 Feb 1;19(2):359-371. doi: 10.1016/j.jtumed.2024.01.002. eCollection 2024 Apr.
Synthetic cannabinoids (SCs), a class of psychoactive compounds emulating the effects of natural cannabis, have prompted addiction and psychosis concerns. However, recent research has suggested potential pharmacological applications, particularly in brain angiogenesis-an essential physiological process for growth, repair, and tissue maintenance, in which new blood vasculature is formed from existing vasculature. This study explored the in vitro ability of the SC 5-fluoro ABICA to enhance new blood formation processes in human brain microvascular endothelial cells (HBMECs).
HBMECs were treated with various concentrations of 5-fluoro ABICA (1 μM, 0.1 μM, 0.01 μM, 0.001 μM, and 0.0001 μM). A comprehensive analysis was conducted, including MTT assays indicating cell viability, wound healing assays indicating migration ability, and tube formation assays indicating the angiogenesis potential of endothelial cells. Additionally, mRNA expression and protein levels of specific pro-angiogenic factors were measured, and the phosphorylation levels of glycogen synthase kinase-3β were detected in treated HBMECs through ELISA, real-time PCR, and western blotting.
Treatment with 5-fluoro ABICA effectively stimulated proliferation, migration, and tube formation in HBMECs in a dose-dependent manner; markedly increased the expression of pro-angiogenic factors; and upregulated levels of phosphorylated-GSK-3β.
Our findings demonstrate that 5-fluoro ABICA stimulates angiogenesis in endothelial cells, thus potentially offering therapeutic options for diseases associated with angiogenesis. However, further research is needed to fully understand the molecular mechanism of 5-fluoro ABICA in angiogenesis, including ethical considerations regarding its use in medical research.
合成大麻素（SCs）是一类模拟天然大麻作用的精神活性化合物，引发了人们对成瘾和精神病的担忧。然而，最近的研究表明其具有潜在的药理学应用，特别是在脑 angiogenesis（血管生成）方面——这是生长、修复和组织维持所必需的生理过程，在此过程中，新的血管系统由现有血管系统形成。本研究探讨了合成大麻素5-氟ABICA在体外增强人脑微血管内皮细胞（HBMECs）中新血液形成过程的能力。
用不同浓度的5-氟ABICA（1μM、0.1μM、0.01μM、0.001μM和0.0001μM）处理HBMECs。进行了全面分析，包括MTT试验以指示细胞活力、伤口愈合试验以指示迁移能力以及管形成试验以指示内皮细胞的血管生成潜力。此外，测量了特定促血管生成因子的mRNA表达和蛋白质水平，并通过ELISA、实时PCR和蛋白质印迹法检测了处理后的HBMECs中糖原合酶激酶-3β的磷酸化水平。
5-氟ABICA处理以剂量依赖的方式有效刺激了HBMECs的增殖、迁移和管形成；显著增加了促血管生成因子的表达；并上调了磷酸化-GSK-3β的水平。
我们的研究结果表明，5-氟ABICA刺激内皮细胞中的血管生成，从而可能为与血管生成相关的疾病提供治疗选择。然而，需要进一步研究以充分了解5-氟ABICA在血管生成中的分子机制，包括其在医学研究中的使用所涉及的伦理考量。
