氨氯地平通过调节红藻等卡拉胶的生物活性保护视网膜神经节细胞损伤,维持眼压:体内和计算机研究。

In silico pharmacology Pub Date : 2025-06-17 eCollection Date: 2025-01-01 DOI:10.1007/s40203-025-00381-x
AshIrbad Nanda, Neha Choudhary, Manorama Patri
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引用次数: 0

摘要

卡拉胶(Carrageenan, Carr)是一种从食用红藻中提取的天然多糖,用于绿色生物合成,也是公认的引起氧化应激的有毒化合物。以哺乳动物(兔)和低等脊椎动物(斑马鱼)为研究对象,探讨carr诱导的视网膜神经节细胞(RGCs)损伤的机制及其与脑的关系。本研究探讨了氨氯地平(AML),一种二氢吡啶钙通道拮抗剂,对carr诱导的rgc损失的调节作用。通过计算机分析AML和Carr,预测它们的蛋白靶点,推断它们与青光眼的药物靶点相互作用。AML与差异表达的青光眼靶点Carr具有较强的结合亲和力,特别是n -甲酰基肽受体、n型钙通道和钠通道蛋白,提示与AML调控作用相关的线索。通过对Carr处理的斑马鱼的组织病理学研究,可以清楚地观察到RGCs层的神经元损伤,而氨氯地平与Carr共给药可降低斑马鱼脑内旋缩细胞计数百分比。在正常血压的兔眼中,角叉菜胶治疗后,局部暴露于AML后,IOP下降40%,IOP在300分钟后恢复到基线水平。总之,本研究涉及硅和体内分析,表明AML对car诱导的氧化应激具有保护作用,促进RGC变性,并具有降低IOP的特性。识别AML类药物调节剂是开发视觉系统障碍新治疗靶点的必要条件。补充信息:在线版本包含补充资料,提供地址为10.1007/s40203-025-00381-x。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Amlodipine protects the retinal ganglionic cell damage maintaining intra ocular pressure by regulating the biological activities of carrageenan like red algae: an in vivo and in-silico study.

Carrageenan (Carr), a natural polysaccharide derived from edible red algae, was used for the green biosynthesis and also recognized as toxic compound causing oxidative stress. The objective was to know the insight mechanism of Carr-induced retino ganglionic cell (RGCs) damage and its connection with brain having two model systems, mammalian (rabbit), lower vertebrates (zebrafish). The present study investigated the modulatory effect of amlodipine (AML), a dihydropyridine calcium channel antagonist, against Carr-induced RGCs loss. AML and Carr were analyzed through in silico study to predict their protein targets and infer their drug-target interactions with glaucoma. AML demonstrated strong binding affinity with differentially expressed glaucoma targets of Carr, specifically N-formyl peptide receptor, N-type calcium channel and sodium channel protein type, suggesting a clue towards the link with the regulatory role of AML. The neuronal damage in RGCs layer was clearly observed through histopathological study in Carr-treated zebrafish while amlodipine co-administration with Carr shown to decrease the percentage of pycknotic cell count in zebrafish brain. A 40% decrease in IOP was observed after exposure to topical AML in the normotensive rabbit eye after carrageenan treatment, with IOP returning to baseline by 300 min. In conclusion, the present study involving in silico and in vivo analysis demonstrated that AML has protective role against carr-induced oxidative stress promoting RGC degeneration with IOP lowering property. Identification of AML like pharmacologic modulators is needed to develop new therapeutic targets for visual system disorders.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00381-x.

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