Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
J Biochem Mol Toxicol. 2024 Nov;38(11):e70019. doi: 10.1002/jbt.70019.
Traumatic brain injury (TBI) causes deficits in neurological function, induces pathological changes, and increases oxidative stress. The current investigation aimed to determine Daidzein's neuroprotective potential in experimental TBI. Initially, the HT-22 cell line exposed to HO underwent in vitro examination, and the results showed that Daidzein had a neuroprotective effect evident from enhanced cell viability and decreased NO generation. Using three different Daidzein doses-1 mg/kg, 5 mg/kg, and 10 mg/kg-in the in vivo experiment, the potential of Daidzein was evaluated against TBI. The neurological severity score (NSS), kondziela's screen test, and elevated plus maze showed improvements after treatment with Daidzein manifested by decreased score, enhanced motor coordination, and anti-anxiety effects. Additionally, Daidzein improved mechanical allodynia and restored the breakdown of the blood-brain barrier. The FTIR spectral analysis showed restoration of the biochemical compositional changes. Furthermore, H & E and Toluidine blue staining revealed an improvement in the histopathological alterations. The RT-qPCR revealed an increase in mRNA expression level of Nrf2, HO-1, and Bcl-2 and the downregulation of Keap-1, Bax and Cleaved caspase-3 expressions. Thus, exhibiting its antioxidant and antiapoptotic potential. The RT-qPCR also manifested a decrease in mRNA expression of GFAP and Iba-1. Further immunohistochemistry results indicated Daidzein's antioxidant and antiapoptotic properties by upregulating Nrf2 and downregulating cleaved caspase-3. Daidzein also lowered the apoptosis index and improved neuronal survival evidenced by flow cytometric analysis. In addition to this, Daidzein notably increased the antioxidant enzyme levels and decreased the oxidative stress markers. The current study's findings point to the neuroprotective potential of the phytoestrogen Daidzein as it lessened neurological abnormalities, decreased oxidative stress, and lowered proapoptotic protein expression.
创伤性脑损伤 (TBI) 导致神经功能缺损、诱导病理变化和增加氧化应激。本研究旨在确定大豆苷元在实验性 TBI 中的神经保护潜力。首先，对 HT-22 细胞系暴露于 HO 进行体外检查，结果表明大豆苷元具有神经保护作用，表现为细胞活力增强和 NO 生成减少。在体内实验中，使用三种不同剂量的大豆苷元（1mg/kg、5mg/kg 和 10mg/kg）评估大豆苷元对 TBI 的潜在作用。用神经功能缺损评分（NSS）、Kondziela 筛检测试和高架十字迷宫进行检测，发现大豆苷元治疗后具有改善作用，表现为评分降低、运动协调增强和抗焦虑作用。此外，大豆苷元改善了机械性痛觉过敏并恢复了血脑屏障的破坏。FTIR 光谱分析显示生化组成变化得到恢复。此外，H&E 和甲苯胺蓝染色显示组织病理学改变得到改善。RT-qPCR 显示 Nrf2、HO-1 和 Bcl-2 的 mRNA 表达水平增加，Keap-1、Bax 和 Cleaved caspase-3 的表达下调。因此，大豆苷元具有抗氧化和抗细胞凋亡作用。RT-qPCR 还显示 GFAP 和 Iba-1 的 mRNA 表达水平降低。进一步的免疫组织化学结果表明，大豆苷元通过上调 Nrf2 和下调 Cleaved caspase-3 发挥抗氧化和抗细胞凋亡作用。大豆苷元还降低了细胞凋亡指数并通过流式细胞术分析改善了神经元存活。除此之外，大豆苷元显著增加了抗氧化酶水平并降低了氧化应激标志物。本研究结果表明，植物雌激素大豆苷元具有神经保护潜力，可减轻神经异常、降低氧化应激和降低促凋亡蛋白表达。
