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

IF 4.7 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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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.