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
{"title":"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","authors":"Kushagra Nagori , Madhulika Pradhan , Kartik T. Nakhate","doi":"10.1016/j.prmcm.2025.100619","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Sappanone A (SAP) is a homoisoflavone derived from the Traditional Chinese Medicine Sumu (<em>Lignum sappan</em>), the dry heartwood of <em>Caesalpinia sappan</em> L. (Leguminosae). Although SAP possesses strong antioxidant properties, its therapeutic potential in Alzheimer’s disease (AD) remains unexplored.</div></div><div><h3>Aim of the study</h3><div>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.</div></div><div><h3>Materials and Methods</h3><div>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.</div></div><div><h3>Results and Discussion</h3><div>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, <em>in-silico</em> molecular docking analysis revealed SAP as a potent agonist of the α7nAR.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"15 ","pages":"Article 100619"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacological Research - Modern Chinese Medicine","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S266714252500048X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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.