Kourat Dallal, Adli Djallal Eddine H, Brahmi Mostapha, Alkholifi Faisal K, Bin Dayel Faten F, Arabi Wafaa, Fauconnier Marie-Laure, Bouzouira Bakhta, Kahloula Khaled, Slimani Miloud, Sweilam Sherouk Hussein
Laboratory of Biotoxicology, Pharmacognosy and Biological Valorization of Plants (LBPVBP), Department of Biology, Faculty of Sciences, University of Dr Moulay Tahar, Saida 20000, Algeria.
Department of Biological Science, Faculty of Natural and Life Sciences, University of Relizane, Relizane 48000, Algeria.
Pharmaceuticals (Basel). 2025 Mar 31;18(4):509. doi: 10.3390/ph18040509.
The purpose of this research was to investigate the effects of bisphenol A (BPA) exposure on neurobehavioral testing in young Wistar rats and to evaluate the therapeutic potential of (TEO) essential oil to attenuate the damage induced by this chemical toxin. : The essential oil was extracted by hydro-distillation (yield of 2.26%), and the characterization by GC-MS indicates that the major components of oil are thymol (63.33%), p-cymene (13.4%), and σ-terpinene (6.69%). Acute BPA intoxication was induced with a dose of 50 mg/kg orally for 60 days. The neurobehavioral evaluation, performed using a comprehensive set of tests including the forced swim test, dark/light box, Morris water maze, open field test, and sucrose preference test, clearly demonstrated that bisphenol A (BPA) exposure induced significant neurobehavioral impairments. : These impairments included reduced exploratory behavior indicative of heightened stress, anxiety, and depressive-like states, as well as deficits in memory and learning. Furthermore, BPA intoxication was associated with metabolic disturbances such as hyperglycemia along with histopathological evidence of brain tissue damage. However, TEO treatment attenuated these adverse effects by restoring neurobehavioral function. Molecular docking analysis revealed an affinity between the major essential oils identified in , BPA, and the 5HT2C receptor and the MAO, AChE, and BChE enzymes, suggesting a potential mechanism underlying BPA's effects on behavior and memory. In addition, TEO also showed an interaction with these molecules, suggesting a therapeutic potential against BPA. These findings underscore the promising role of TEO in mitigating the poisonous effects of BPA and pave the way for additional research into the molecular mechanisms and therapeutic uses of natural bioactive compounds for the prevention and treatment of toxic diseases. Thymol, the major compound in TEO, exhibited activity related to the dopamine and serotonin pathways, so it could have potential antidepressant properties. : Thymol might be a promising candidate for the treatment of neurodegenerative and neurological disorders such as depression, Parkinson's disease, and Alzheimer's disease while also preventing histological damage in the brain.
本研究的目的是调查双酚A(BPA)暴露对幼年Wistar大鼠神经行为测试的影响,并评估百里香(TEO)精油减轻这种化学毒素所致损伤的治疗潜力。通过水蒸馏法提取精油(得率为2.26%),气相色谱-质谱联用(GC-MS)表征表明,该精油的主要成分是百里香酚(63.33%)、对伞花烃(13.4%)和σ-萜品烯(6.69%)。以50 mg/kg的剂量口服诱导急性BPA中毒,持续60天。使用包括强迫游泳试验、明暗箱试验、莫里斯水迷宫试验、旷场试验和蔗糖偏好试验在内的一套综合测试进行神经行为评估,结果清楚地表明,双酚A(BPA)暴露会导致明显的神经行为损伤。这些损伤包括探索行为减少,表明应激、焦虑和抑郁样状态加剧,以及记忆和学习缺陷。此外,BPA中毒与代谢紊乱如高血糖以及脑组织损伤的组织病理学证据有关。然而,TEO治疗通过恢复神经行为功能减轻了这些不良反应。分子对接分析揭示了TEO中鉴定出的主要精油、BPA与5HT2C受体以及单胺氧化酶(MAO)、乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)之间的亲和力,这表明BPA对行为和记忆产生影响的潜在机制。此外,TEO也显示出与这些分子的相互作用,表明其对BPA具有治疗潜力。这些发现强调了TEO在减轻BPA毒性作用方面的前景,并为进一步研究天然生物活性化合物预防和治疗中毒性疾病的分子机制及治疗用途铺平了道路。百里香酚是TEO中的主要化合物,表现出与多巴胺和5-羟色胺途径相关的活性,因此它可能具有潜在的抗抑郁特性。百里香酚可能是治疗神经退行性疾病和神经疾病如抑郁症、帕金森病和阿尔茨海默病的有前景的候选药物,同时还能预防脑部的组织学损伤。