The therapeutic effect of phenolics on neurodegenerative diseases has been attributed to their potent antioxidant properties. In the present study, the neuroprotective activities of vanillin and vanillic acid were investigated in Fe2+- induced oxidative toxicity in brain tissues by investigating their therapeutic effects on oxidative imbalance, cholinergic and nucleotide-hydrolyzing enzymes activities, dysregulated metabolic pathways. Their cytotoxicity was investigated in hippocampal neuronal cell lines (HT22). The reduced glutathione level, SOD and catalase activities were ameliorated in tissues treated with the phenolics, with concomitant depletion of malondialdehyde and nitric oxide levels. They inhibited acetylcholinesterase and butyrylcholinesterase activities, while concomitantly elevated ATPase activity. Treatment with vanillin led to restoration of oxidative-depleted metabolites and reactivation of the pentose phosphate and purine metabolism pathways, with concomitant activation of pathways for histidine and selenoamino metabolisms. While vanillic acid restored and reactivated oxidative-depleted metabolites and pathways but did not activate any additional pathway. Both phenolics portrayed good binding affinity for catalase, with vanillic acid having the higher binding energy of -7.0 kcal/mol. Both phenolics were not cytotoxic on HT22 cells, and their toxicity class were predicted to be 4. Only vanillin was predicted to be permeable across the blood brain barrier (BBB). These results insinuate that vanillin and vanillic acid confer a neuroprotective effect on oxidative brain damage, when vanillin being the most potent.

中文翻译：

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香草醛和香草酸通过改善与 Fe2+ 诱导的脑组织损伤相关的代谢并发症来调节抗氧化防御系统。

酚类物质对神经退行性疾病的治疗作用归因于其强大的抗氧化特性。在本研究中，香草醛和香草酸在 Fe2+ 诱导的脑组织氧化毒性中的神经保护活性通过研究它们对氧化失衡、胆碱能和核苷酸水解酶活性、代谢途径失调的治疗作用进行了研究。在海马神经元细胞系 (HT22) 中研究了它们的细胞毒性。在用酚类物质处理的组织中，降低的谷胱甘肽水平、SOD 和过氧化氢酶活性得到改善，伴随着丙二醛和一氧化氮水平的消耗。它们抑制乙酰胆碱酯酶和丁酰胆碱酯酶的活性，同时提高 ATP 酶的活性。香草醛处理导致氧化耗尽的代谢物的恢复和磷酸戊糖和嘌呤代谢途径的重新激活，同时组氨酸和硒氨基代谢途径的激活。虽然香草酸恢复并重新激活了氧化耗尽的代谢物和途径，但没有激活任何额外的途径。两种酚类都对过氧化氢酶具有良好的结合亲和力，香草酸具有 -7.0 kcal/mol 的更高结合能。两种酚类物质对 HT22 细胞均无细胞毒性，预计它们的毒性等级为 4。预计只有香草醛可渗透血脑屏障 (BBB)。这些结果暗示香草醛和香草酸对氧化性脑损伤具有神经保护作用，此时香草醛最有效。