Sappanone A mitigates cognitive impairment and oxidative stress through modulation of α7 nicotinic acetylcholine receptor in rats with trimethyltin-induced Alzheimer’s disease-like condition

Kushagra Nagori , Madhulika Pradhan , Kartik T. Nakhate
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Abstract

Background

Sappanone A (SAP) is a homoisoflavone derived from the Traditional Chinese Medicine Sumu (Lignum sappan), the dry heartwood of Caesalpinia sappan L. (Leguminosae). Although SAP possesses strong antioxidant properties, its therapeutic potential in Alzheimer’s disease (AD) remains unexplored.

Aim of the study

We evaluated the ameliorative effects of SAP on AD-like pathology induced in rats by the neurotoxicant trimethyltin (TMT). Additionally, the involvement of the α7 nicotinic acetylcholine receptor (α7nAR) in the underlying effects of SAP was investigated.

Materials and Methods

Seven days after TMT (8 mg/kg, i.p.) exposure, SAP (25 and 50 mg/kg, oral) was administered for two weeks, and cognitive abilities were screened by the Morris water maze test. The estimation of brain glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and malonaldehyde (MDA) contents was also conducted. Molecular docking studies were carried out to evaluate the binding affinity of SAP towards α7nAR.

Results and Discussion

TMT-treated rats exhibited significant deficits in learning and memory performance. This was accompanied by decreased contents of GSH, CAT, and SOD, and elevated MDA levels in the brain. Administration of SAP significantly improved cognitive performance and restored oxidative stress markers. However, co-administration of α7nAR blocker methyllycaconitine attenuated these actions. Moreover, in-silico molecular docking analysis revealed SAP as a potent agonist of the α7nAR.

Conclusion

SAP improved TMT-induced cognitive impairments, mainly due to its strong antioxidant effects in the brain, facilitated through α7nAR modulation. These findings suggest that SAP could serve as a promising candidate for treating cognitive dysfunction linked to oxidative stress.

Abstract Image

三甲基锡诱导的阿尔茨海默病样大鼠α7烟碱胆碱受体调节对认知障碍和氧化应激的影响
sappanone A (SAP)是一种从豆科植物杉木(Caesalpinia sappan L.)的干心材苏木(Lignum sappan)中提取的同源异黄酮。尽管SAP具有很强的抗氧化特性,但其在阿尔茨海默病(AD)中的治疗潜力仍未被探索。研究目的:观察SAP对神经毒物三甲基锡(TMT)致大鼠ad样病理的改善作用。此外,还研究了α7烟碱乙酰胆碱受体(α7nAR)在SAP的潜在作用中的作用。材料与方法TMT (8 mg/kg, i.p.)暴露后第7天,给予SAP(25和50 mg/kg,口服)2周,通过Morris水迷宫试验筛选认知能力。测定脑内谷胱甘肽(GSH)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量。通过分子对接研究来评价SAP对α7nAR的结合亲和力。结果与讨论经tmt治疗的大鼠在学习和记忆方面表现出明显的缺陷。大脑中GSH、CAT和SOD含量降低,MDA水平升高。服用SAP可显著改善认知能力并恢复氧化应激标志物。然而,α7nAR阻滞剂甲基莱卡乌碱的联合使用减弱了这些作用。此外,硅分子对接分析显示SAP是α7nAR的有效激动剂。结论sap改善tmt诱导的认知功能障碍,主要是通过α7nAR调节其在脑内的强抗氧化作用。这些发现表明,SAP可以作为治疗与氧化应激相关的认知功能障碍的有希望的候选者。
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