Nanda AshIrbad, Choudhary Neha, Patri Manorama
Present Address: Department of Pharmacology, School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Jatni, Bhubaneswar, 752050 Odisha India.
Center for Computational Biology and Bioinformatics, School of Life Sciences, Central University Himachal Pradesh, Himachal Pradesh, Dharmasala, Kanga 176206 India.
In Silico Pharmacol. 2025 Jun 17;13(2):91. doi: 10.1007/s40203-025-00381-x. eCollection 2025.
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.
The online version contains supplementary material available at 10.1007/s40203-025-00381-x.
角叉菜胶(Carr)是一种从可食用红藻中提取的天然多糖,用于绿色生物合成,但也被认为是一种会导致氧化应激的有毒化合物。目的是通过两种模型系统,即哺乳动物(兔子)和低等脊椎动物(斑马鱼),了解角叉菜胶诱导视网膜神经节细胞(RGCs)损伤的内在机制及其与大脑的联系。本研究调查了二氢吡啶类钙通道拮抗剂氨氯地平(AML)对角叉菜胶诱导的RGCs损失的调节作用。通过计算机模拟研究分析了AML和角叉菜胶,以预测它们的蛋白质靶点,并推断它们与青光眼的药物-靶点相互作用。AML对角叉菜胶差异表达的青光眼靶点,特别是N-甲酰肽受体、N型钙通道和钠通道蛋白类型,表现出很强的结合亲和力,这为AML的调节作用提供了线索。通过组织病理学研究,在角叉菜胶处理的斑马鱼中清楚地观察到RGCs层的神经元损伤,而氨氯地平与角叉菜胶共同给药可降低斑马鱼脑中固缩细胞计数的百分比。在角叉菜胶处理后的正常血压兔眼中,局部应用AML后眼压降低了40%,300分钟后眼压恢复到基线水平。总之,本研究通过计算机模拟和体内分析表明,AML对角叉菜胶诱导的氧化应激具有保护作用,可促进RGCs变性并具有降低眼压的特性。需要鉴定类似AML的药理调节剂,以开发针对视觉系统疾病的新治疗靶点。
在线版本包含可在10.1007/s40203-025-00381-x获取的补充材料。