Prakash Chandra, Tyagi Jyoti, Singh Kumari Vandana, Kumar Gautam, Sharma Deepak
Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
Department of Laboratory Medicine, Jaiprakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, 110029, India.
Metab Brain Dis. 2025 Jan 6;40(1):87. doi: 10.1007/s11011-024-01526-1.
Aluminium is a common metallic toxicant that easily penetrates the brain and exerts severe pathological effects e.g., oxidative stress, inflammation and neurodegeneration. Eugenol is a natural phenolic compound possessing numerous therapeutic properties including antioxidant, anti-inflammatory and neuroprotective. The compound has also been reported to interfere with important transcription factors like STAT3 and NF-кB. Thus, the present study intended to explore the therapeutic potential of eugenol in aluminium neurotoxicity. Rats were administered AlCl (100 mg/kg b. wt., orally) and eugenol (200 mg/kg b. wt., orally) alone or in combination for 45 days. The results revealed that AlCl administration increases acetylcholinesterase (AChE) activity, lipid peroxidation (LPO), and protein oxidation (PO) along with decreasing superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) content in the cortex and hippocampus regions of the brain. Moreover, AlCl induces neuronal loss and astroglial activation in both brain areas. The study further revealed that AlCl also increases the expression of transcription factors STAT3 and NF-кB in neurons and astrocytes of the cortex and hippocampus. However, co-administration of eugenol with AlCl restored the enzymatic activities of AChE, SOD and CAT, and GSH content, and rescued the cortex and hippocampus from LPO, PO, neuronal loss and astroglial activation. Furthermore, the study reported that eugenol reverses the expression pattern of STAT3 and NF-кB in AlCl-intoxicated rats. In conclusion, the study suggests that eugenol ameliorates oxidative stress, neuronal loss and reactive astrogliosis in aluminium-induced neurotoxicity by inhibiting signalling molecules, STAT3 and NF-кB.
铝是一种常见的金属毒物，容易穿透大脑并产生严重的病理效应，如氧化应激、炎症和神经退行性变。丁香酚是一种天然酚类化合物，具有多种治疗特性，包括抗氧化、抗炎和神经保护作用。据报道，该化合物还会干扰重要的转录因子，如信号转导与转录激活因子3（STAT3）和核因子κB（NF-кB）。因此，本研究旨在探讨丁香酚在铝神经毒性中的治疗潜力。给大鼠单独或联合口服氯化铝（100毫克/千克体重）和丁香酚（200毫克/千克体重），持续45天。结果显示，给予氯化铝会增加大脑皮质和海马区域的乙酰胆碱酯酶（AChE）活性、脂质过氧化（LPO）和蛋白质氧化（PO），同时降低超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性以及谷胱甘肽（GSH）含量。此外，氯化铝会诱导两个脑区的神经元丢失和星形胶质细胞活化。研究还进一步表明，氯化铝还会增加大脑皮质和海马神经元及星形胶质细胞中转录因子STAT3和NF-кB的表达。然而，丁香酚与氯化铝联合给药可恢复AChE、SOD和CAT的酶活性以及GSH含量，并使大脑皮质和海马免受LPO、PO、神经元丢失和星形胶质细胞活化的影响。此外，该研究报告称，丁香酚可逆转氯化铝中毒大鼠中STAT3和NF-кB的表达模式。总之，该研究表明，丁香酚通过抑制信号分子STAT3和NF-кB，改善铝诱导的神经毒性中的氧化应激、神经元丢失和反应性星形胶质细胞增生。
