Iftikhar Kanwal, Niaz Maryam, Shahid Maha, Zehra Sumbul, Afzal Taj, Faizi Shaheen, Simjee Shabana Usman
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Hippocampus. 2024 Oct;34(10):540-550. doi: 10.1002/hipo.23630. Epub 2024 Aug 6.
Neural progenitor cells (NPCs) reside in the brain and participate in the mechanism of neurogenesis that permits the brain to generate the building blocks for enhancement of cognitive abilities and acquisition of new skills. The existence of NPCs in brain has opened a novel dimension of research to explore their potential for treatment of various neurodegenerative disorders. The present study provides novel insights into the intracellular mechanisms in neuronal cells proliferation, maturation and differentiation regulated by Quinic acid (QA). Furthermore, this study might help in discovery and development of lead molecule that can overcome the challenges in the treatment of neurodegenerative diseases. The growth supporting effect of QA was studied using MTT assay. For that purpose, hippocampal cell cultures of neonatal rats were treated with different concentrations of QA and incubated for 24, 48 and 72 h. Gene and protein expressions of the selected molecular markers nestin, neuron-specific class III beta-tubulin (Tuj-1), neuronal nuclear protein (NeuN), neuronal differentiation 1 (NeuroD1), glial fibrillary acidic protein (GFAP), neuroligin (NLGN) and vimentin were analyzed. QA-induced cell proliferation and differentiation of hippocampal progenitor cells was also accompanied by significantly increased expression of progenitor and immature neuronal marker, mature neuronal marker and differentiating factor, that is, nestin, Tuj-1, NeuN and NeuroD1, respectively. On the other hand, vimentin downregulation and constant GFAP expression were observed following QA treatment. Additionally, the effects of QA on the recovery of stressed cells was studied using in vitro model of oxygen glucose deprivation (OGD). It was observed that hippocampal cells were able to recover from OGD following the treatment with QA. These findings suggest that QA treatment promotes hippocampal neurogenesis by proliferating and differentiating of NPCs and recovers neurons from stress caused by OGD. Thus, the neurogenic potential of QA can be explored for the treatment of neurodegenerative disorders.
神经祖细胞（NPCs）存在于大脑中，并参与神经发生机制，使大脑能够生成增强认知能力和获取新技能的基础组成部分。大脑中NPCs的存在开启了一个新的研究维度，以探索它们治疗各种神经退行性疾病的潜力。本研究为奎尼酸（QA）调节神经元细胞增殖、成熟和分化的细胞内机制提供了新的见解。此外，本研究可能有助于发现和开发能够克服神经退行性疾病治疗挑战的先导分子。使用MTT法研究了QA的生长支持作用。为此，用不同浓度的QA处理新生大鼠的海马细胞培养物，并孵育24、48和72小时。分析了所选分子标记物巢蛋白、神经元特异性III类β-微管蛋白（Tuj-1）、神经元核蛋白（NeuN）、神经元分化1（NeuroD1）、胶质纤维酸性蛋白（GFAP）、神经连接蛋白（NLGN）和波形蛋白的基因和蛋白表达。QA诱导的海马祖细胞增殖和分化还分别伴随着祖细胞和未成熟神经元标记物、成熟神经元标记物和分化因子，即巢蛋白、Tuj-1、NeuN和NeuroD1表达的显著增加。另一方面，QA处理后观察到波形蛋白下调和GFAP表达恒定。此外，使用氧葡萄糖剥夺（OGD）体外模型研究了QA对应激细胞恢复的影响。观察到海马细胞在QA处理后能够从OGD中恢复。这些发现表明，QA处理通过NPCs的增殖和分化促进海马神经发生，并使神经元从OGD引起的应激中恢复。因此，可以探索QA的神经发生潜力用于治疗神经退行性疾病。
