Zhang Meiya, Huang Xirui, Dai Mengxiang, Zhang Shunbo, Yin Chao, You Qiuyun
School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Sci Rep. 2025 Aug 7;15(1):28873. doi: 10.1038/s41598-025-14303-6.
Sleep deprivation (SD) causes learning memory and cognitive impairment. Salvia miltiorrhiza Bunge (Danshen, DS), a medicinal plant in the family Labiatae, has been traditionally used for sleep-related disorders. Previous studies have shown that DS can ameliorate SD-induced cognitive impairment. However, the underlying mechanisms for its pharmacological effects remain unclear. This study aimed to evaluate the protective effects and mechanisms of DS extract against cognitive impairment in SD rats. UPLC-QTOF/MS was used to analyze DS extracts. The SD model was constructed utilizing a modified multi-platform aquatic sleep deprivation procedure that lasted 21 days. The Morris water maze test (MWM), hematoxylin and eosin (H&E) staining, and enzyme-linked immunosorbent assay (ELISA) were used to assess learning and memory ability, hippocampus injury, and serum inflammation, respectively. An integrated strategy of serum metabolomics combined with network analysis was used to explore the potential mechanisms by which DS exerts pharmacological effects. Molecular docking and experiments were used for further validation. UPLC-QTOF-MS/MS identified 32 diterpenoids in DS extract. The results showed that DS (1.35 and 2.70 g/kg) significantly improved spatial learning and memory abilities in SD rats while also reducing hippocampus pathological damage and serum inflammation. Serum metabolomics showed that DS modulated 26 differential metabolites, mainly involved in Glycerophospholipid metabolism, Glycerolipid metabolism, Phosphatidylinositol signaling system, and One carbon pool by folate. Network analysis screened 145 putative targets for DS to alleviate SD-induced cognitive impairment, involved in inflammation regulation and metabolic modulation. Integrated analyses of metabolomics and network analysis indicated that PIK3CA was a key target for DS's regulatory effects, primarily engaged in the regulation of phosphatidylinositol phosphate metabolism. Validation experiments revealed that all eight components of DS extracts had a higher binding ability with PIK3CA, and DS restored the SD-induced abnormal expression of PIK3CA. Our study provides new insights into the development of DS as a dietary supplement for treating SD-induced cognitive impairment.
睡眠剥夺（SD）会导致学习记忆和认知障碍。丹参（Salvia miltiorrhiza Bunge，DS）是唇形科的一种药用植物，传统上用于治疗与睡眠相关的疾病。先前的研究表明，丹参可以改善睡眠剥夺诱导的认知障碍。然而，其药理作用的潜在机制仍不清楚。本研究旨在评估丹参提取物对睡眠剥夺大鼠认知障碍的保护作用及其机制。采用超高效液相色谱-四极杆飞行时间质谱联用仪（UPLC-QTOF/MS）分析丹参提取物。利用改良的多平台水生睡眠剥夺程序构建睡眠剥夺模型，持续21天。分别采用莫里斯水迷宫试验（MWM）、苏木精-伊红（H&E）染色和酶联免疫吸附测定（ELISA）来评估学习记忆能力、海马损伤和血清炎症。采用血清代谢组学结合网络分析的综合策略来探索丹参发挥药理作用的潜在机制。利用分子对接和实验进行进一步验证。UPLC-QTOF-MS/MS鉴定出丹参提取物中的32种二萜类化合物。结果表明，丹参（1.35和2.70 g/kg）显著提高了睡眠剥夺大鼠的空间学习和记忆能力，同时还减少了海马病理损伤和血清炎症。血清代谢组学表明，丹参调节了26种差异代谢物，主要涉及甘油磷脂代谢、甘油酯代谢、磷脂酰肌醇信号系统和叶酸一碳池。网络分析筛选出145个丹参减轻睡眠剥夺诱导的认知障碍的潜在靶点，涉及炎症调节和代谢调节。代谢组学和网络分析的综合分析表明，PIK3CA是丹参调节作用的关键靶点，主要参与磷脂酰肌醇磷酸代谢的调节。验证实验表明，丹参提取物的所有八种成分与PIK3CA具有更高的结合能力，并且丹参恢复了睡眠剥夺诱导的PIK3CA异常表达。我们的研究为将丹参开发为治疗睡眠剥夺诱导的认知障碍的膳食补充剂提供了新的见解。
