UHPLC-Q Exactive-Orbitrap-MS and Network Pharmacology Analyses to Investigate the Mechanism by Which Danggui-Shaoyao-San Affects 27-OHC-induced Cell Damage in SH-SY5Y/C6 Coculture

Overview

Journal BMC Complement Med Ther

Publisher Biomed Central

Specialty Rehabilitation Medicine

Date 2025 Feb 24

PMID 39994624

Authors

Yi Huang

Yingying Zhai

Di Zhao

Mingan Wu

Qi Shen

Wei Zhao

Qi Wang

Limei Yao

Weirong Li

Affiliations

Soon will be listed here.

Abstract

Background: Danggui-Shaoyao-San (DSS) is a classic Chinese medicine formula that has been extensively studied for its efficacy in treating Alzheimer's disease (AD). However, its mechanism of action is still unclear.

Methods: In this study, UHPLC-Q Exactive-Orbitrap-MS was used to analyze and identify the compounds in DSS. Network pharmacology was used to analyze the common targets of drug-containing serum chemistries and AD, as well as the AD pathways in which drug-containing serum chemistries may be involved. The 27-OHC-induced SH-SY5Y/C6 coculture cell injury model was used to explore the mechanism of action of DSS in the treatment of AD.

Results: UHPLC-Q Exactive-Orbitrap-MS analysis identified 73 chemical constituents in DSS aqueous extract and 39 compounds in drug-containing serum. According to network pharmacology analysis, DSS and AD share 181 common targets, with interleukin-6 (IL-6) and tumor necrosis factor (TNF) being the main effective targets. Furthermore, DSS may treat AD through the modulation of lipid metabolism-related pathways and the interleukin-17 (IL-17) signaling pathway. 27-hydroxycholesterol acid (27-OHC) significantly reduced the viability of SH-SY5Y cells and C6 cells in vitro, while DSS administration upregulated the expression of cytochrome P450 46A1 (CYP46A1) and cytochrome P450 7B1 (CYP7B1) enzymes and reduced cholesterol levels in SH-SY5Y cells. Additionally, DSS decreased reactive oxygen species (ROS) levels and increased glutathione (GSH) levels in coculture systems. DSS downregulated the expression of IL-17 in 27-OHC-injured SH-SY5Y cells and downregulated the expression of TNF-α, IL-6 and transforming growth factor-β1 (TGF-β1) in 27-OHC-injured C6 cells.

Conclusion: This study revealed the effective components, targets and mechanisms of DSS in the treatment of AD, highlighting the significant potential of DSS in treating this disease.

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