Danggui-Shaoyao-San Can Ameliorate Alzheimer's Disease by Inhibiting Hippocampal Neuron Apoptosis: Findings from Serum Pharmacology.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S490900

Kai-Xin Zhang, Ji-Wei Zhang, Yan-Hong Jiang, Yi-Ran Wang, Zhen-Ling Liu, Peng-Li Ding, Xiang-Ying Wang, Wen-Qiang Cui, Xiang-Qing Xu, Ya-Han Wang

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Abstract

Background: Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine prescription with a history of nearly 2000 years, originally widely used for gynecological diseases, and in recent years research has found that DSS also has a good therapeutic effect on Alzheimer's disease (AD).

Purpose: The objective is to investigate the metabolic components of the DSS in the blood and the potential mechanisms for AD.

Materials and methods: Liquid chromatography‒mass spectrometry (LC-MS) combined with gas chromatography‒mass spectrometry (GC-MS) based non-targeted metabolomics were used to conduct in-depth research. Serum Pharmacology was used to analyze potential mechanisms of DSS for AD. C57BL/6J mice and Hippocampal neuronal cell line (HT-22) were used to prepare the AD model. Enzyme linked immunosorbent assay (Elisa), quantitative polymerase chain reaction (q-PCR), Morris water maze,Western blot (WB), Immunohistochemical and Immunofluorescence were used to study the effect of DSS on AD. Flow cytometry and Cell Counting Kit-8 (CCK-8) reveal the effect of DSS serum on HT-22 proliferation and apoptosis.

Results: A total of 57 metabolic components were screened in DSS serum. Serum Pharmacology revealed that the calcium signaling pathway and cAMP/PKA/CREB pathway may be a potential mechanism through which DSS treated AD. DSS can reduce aberrant phosphorylation of Tau and modulates cAMP/PKA/CREB pathway to improve cognition and apoptosis in AD mice. DSS serum can increase the cell viability of HT-22 and reduce apoptosis mainly by alleviating mitochondrial calcium overloading.

Conclusion: DSS can modulate the calcium signaling pathway and enhance the cAMP/PKA/CREB signaling pathway to ameliorate Tau aberrant phosphorylation, cognitive deficits and neuronal apoptosis after AD.

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当归少药散通过抑制海马神经元凋亡改善阿尔茨海默病的血清药理学研究。

背景：当归少药散（DSS）是一种具有近2000年历史的中药方剂，最初广泛用于妇科疾病，近年来研究发现，DSS对阿尔茨海默病（AD）也有很好的治疗效果。目的：研究血液中DSS的代谢成分和AD的潜在机制。材料与方法：采用液相色谱-质谱（LC-MS）结合气相色谱-质谱（GC-MS）的非靶向代谢组学进行深入研究。采用血清药理学方法分析DSS治疗AD的可能机制。采用C57BL/6J小鼠和海马神经元细胞系HT-22制备AD模型。采用酶联免疫吸附法（Elisa）、定量聚合酶链反应（q-PCR）、Morris水迷宫法、免疫印迹法（WB）、免疫组织化学法和免疫荧光法研究DSS对AD的影响。流式细胞术和细胞计数试剂盒-8 （CCK-8）显示DSS血清对HT-22细胞增殖和凋亡的影响。结果：从DSS血清中共筛选出57种代谢成分。血清药理学结果显示，钙信号通路和cAMP/PKA/CREB通路可能是DSS治疗AD的潜在机制。DSS可减少Tau异常磷酸化，调节cAMP/PKA/CREB通路，改善AD小鼠的认知和细胞凋亡。DSS血清主要通过减轻线粒体钙超载而提高HT-22细胞活力，减少细胞凋亡。结论：DSS可调节钙信号通路，增强cAMP/PKA/CREB信号通路，改善AD后Tau异常磷酸化、认知缺陷和神经元凋亡。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.