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在H9c2细胞上新合成的Cannabidiol衍生物的药理学评估

Kitti Szőke^1,2, Richárd Kajtár¹, Alexandra Gyöngyösi¹

¹Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary.

Antioxidants (Basel, Switzerland)

|September 28, 2023

概括

新的大麻素 (CBD) 衍生物显示出对心肌细胞细胞死亡的保护作用. 这些通过曼尼赫类反应合成的新型化合物,通过减少细胞毒性,为心血管疾病提供潜在的治疗益处.

科学领域:

药理学药理学是指药理学的学科.
药用化学医学化学
心血管研究研究心血管研究

背景情况:

Cannabidiol (CBD) 是一种来自 *Cannabis sativa * 的非精神活性植物性cannabinoid,它表现出各种各样的药理作用,包括在心血管疾病中的潜在应用.
然而,CBD的治疗用途受到生物可用性差,水溶性低和可变的药理动力学限制.
化学衍生是一种提高CBD治疗特性的策略.

研究的目的:

在芳香环上使用曼尼赫式反应合成新型CBD衍生物.
评估这些新衍生物在心肌细胞中对氧化应激和低氧/低氧化 (H/R) 的保护作用.
为了比较衍生品与原始CBD化合物的疗效.

主要方法:

通过曼尼赫式反应合成三种新的CBD衍生物.
使用MTT试验评估细胞活力.
通过Trypan蓝色排除和乳酸脱酶 (LDH) 释放试验评估细胞死亡和膜完整性.
使用总抗氧化能力 (TAC) 试验测量直接抗氧化活性.
使用西方布洛特的抗氧化蛋白表达 (HO-1,SOD,catalase) 的分析.

主要成果:

合成的CBD衍生物在H9c2心肌细胞中显示出对H/R诱导的细胞死亡的保护作用,CBD2显示出特别有效.
CBD表现出最高的直接抗氧化活性.
用CBD衍生物和CBD进行预处理,差异调节了抗氧化蛋白的水平.
pIC50值表明化合物之间具有不同的抗氧化能力.

结论:

新合成的CBD衍生物有效地降低了心肌细胞中由氧化应激和H/R引起的细胞毒性.
这些衍生物在H9c2细胞中表现出与CBD相似或更强的保护作用.
这项研究强调了化学修饰的CBD作为治疗心血管疾病的治疗剂的潜力,其中包括氧化应激.

关键词:

抗氧化剂是一种抗氧化剂.在Cannabidiol中使用.大麻素是一种大麻素.模拟的缺氧/再输血.

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