Bushen Tiansui Formula (BSTSF) is a traditional Chinese medicine prescription. It has been widely applied to treat Alzheimer’s disease (AD) in the clinic; however, the mechanisms underlying its effects remain largely unknown. In this study, we used a rat AD model to study the effects of BSTSF on cognitive performance, and UPLC-MS/MS-based metabolomic and lipidomic analysis was further performed to identify significantly altered metabolites in the cerebral cortices of AD rats and determine the effects of BSTSF on the metabolomic and lipidomic profiles in the cerebral cortices of these animals. The results revealed that the levels of 47 metabolites and 30 lipids primarily associated with sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism were significantly changed in the cerebral cortices of AD rats. Among the altered lipids, ceramides, phosphatidylethanolamines, lysophosphatidylethanolamines, phosphatidylcholines, lysophosphatidylcholines, phosphatidylserines, sphingomyelins, and phosphatidylglycerols showed robust changes. Moreover, 34 differential endogenous metabolites and 21 lipids, of which the levels were mostly improved in the BSTSF treatment group, were identified as potential therapeutic targets of BSTSF against AD. Our results suggest that lipid metabolism is highly dysregulated in the cerebral cortices of AD rats, and BSTSF may exert its neuroprotective mechanisms by restoring metabolic balance, including that of sphingolipid metabolism, glycerophospholipid metabolism, alanine, aspartate, and glutamate metabolism, and D-glutamine and D-glutamate metabolism. Our data may lead to a deeper understanding of the AD-associated metabolic profile and shed new light on the mechanism underlying the therapeutic effects of BSTSF.

中文翻译：

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整合的代谢组学和脂质组学分析揭示了补肾天遂配方在Aβ1-42诱导的阿尔茨海默氏病大鼠模型中的神经保护机制。

补肾天岁配方（BSTSF）是一种中药处方。它已在临床上广泛用于治疗阿尔茨海默氏病（AD）；然而，影响其作用的机制仍然未知。在这项研究中，我们使用大鼠AD模型研究BSTSF对认知功能的影响，并进一步进行了基于UPLC-MS / MS的代谢组学和脂质组学分析，以鉴定AD大鼠大脑皮层中代谢产物的显着改变并确定BSTSF对这些动物大脑皮层的代谢组学和脂质组学谱的影响。结果表明，AD大鼠脑皮质中主要与鞘脂代谢，甘油磷脂代谢和亚油酸代谢相关的47种代谢物和30种脂质的水平发生了显着变化。在改变的脂质中，神经酰胺，磷脂酰乙醇胺，溶血磷脂酰乙醇胺，磷脂酰胆碱，溶血磷脂酰胆碱，磷脂酰丝氨酸，鞘磷脂和磷脂酰甘油显示出强劲的变化。此外，BSTSF治疗组中34种差异性内源性代谢物和21种脂质的水平得到了最大程度的改善，被确定为BSTSF抗AD的潜在治疗靶标。我们的研究结果表明，AD大鼠的大脑皮质中脂质代谢高度失调，BSTSF可能通过恢复代谢平衡来发挥其神经保护机制，包括鞘脂代谢，甘油磷脂代谢，丙氨酸，天冬氨酸和谷氨酸代谢以及D-谷氨酰胺。和D-谷氨酸代谢。