Li Hongli, Tan Yejun, Cheng Xin, Zhang Zheyu, Huang Jianhua, Hui Shan, Zhu Lemei, Liu Yuqing, Zhao Di, Liu Zhao, Peng Weijun
Department of Integrated Traditional Chinese and Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Mental Disorder, Changsha, China.
Front Pharmacol. 2022 Oct 20;13:990307. doi: 10.3389/fphar.2022.990307. eCollection 2022.
Bushen Tiansui Formula (BSTSF) is a traditional formulation of Chinese medicine that has been used to treat Alzheimer's disease (AD) for decades; however, the underlying mechanisms by which this formula achieves such therapeutic effects have yet to be elucidated. To investigate the neuroprotective mechanisms of BSTSF against AD by analyzing metabolite profiles in the hippocampus and cortex of AD rats. The rat models of AD were established by the injection of Aβ. The Morris water maze (MWM) test was performed to evaluate the effect of BSTSF treatment on cognitive dysfunction. Hematoxylin and eosin (HE) staining was used to assess the effect of BSTSF on typical AD pathologies. Underlying mechanisms were investigated using LC-MS/MS-based untargeted metabolomics analysis of the cerebral cortex and hippocampus. BSTSF significantly improved memory deficits and the typical histopathological changes of AD rats. Untargeted metabolomics analysis showed that 145 and 184 endogenous metabolites in the cerebral cortex and hippocampus, respectively, were significantly different in the BSTSF group when compared with the AD group. The differential metabolites in the cerebral cortex were primarily involved in cysteine and methionine metabolism, while those in the hippocampus were mainly involved in d-Glutamine and d-glutamate metabolism. In the present study, we confirmed the neuroprotective effects of BSTSF treatment against AD using a rat model. Our findings indicate that the BSTSF-mediated protective effects were associated with amelioration of metabolic disorders in the hippocampus and cerebral cortex.
补肾添髓方（BSTSF）是一种传统的中药配方，已用于治疗阿尔茨海默病（AD）数十年；然而，该配方实现这种治疗效果的潜在机制尚未阐明。通过分析AD大鼠海马和皮质中的代谢物谱来研究BSTSF对AD的神经保护机制。通过注射Aβ建立AD大鼠模型。进行莫里斯水迷宫（MWM）试验以评估BSTSF治疗对认知功能障碍的影响。苏木精-伊红（HE）染色用于评估BSTSF对典型AD病理的影响。使用基于液相色谱-串联质谱（LC-MS/MS）的非靶向代谢组学分析对大脑皮质和海马进行潜在机制研究。BSTSF显著改善了AD大鼠的记忆缺陷和典型的组织病理学变化。非靶向代谢组学分析表明，与AD组相比，BSTSF组大脑皮质和海马中分别有145种和184种内源性代谢物存在显著差异。大脑皮质中的差异代谢物主要参与半胱氨酸和蛋氨酸代谢，而海马中的差异代谢物主要参与D-谷氨酰胺和D-谷氨酸代谢。在本研究中，我们使用大鼠模型证实了BSTSF治疗对AD的神经保护作用。我们的研究结果表明，BSTSF介导的保护作用与改善海马和大脑皮质中的代谢紊乱有关。
