Daqinjiao Decoction Ameliorates CSVD via RXR‐γ/PPAR‐γ/VEGF‐α Pathway: Insights From Transcriptome Sequencing and Network Pharmacology

TL;DR

This study shows that Daqinjiao Decoction helps treat cerebral small vessel disease by reducing inflammation and protecting brain tissue through a specific molecular pathway.

Contribution

The study reveals a novel molecular mechanism involving the RXR-γ/PPAR-γ/VEGF-α pathway for the therapeutic effects of Daqinjiao Decoction on CSVD.

Findings

DQJD reduced inflammation and pathological damage in the hippocampus and cortex of CCH rats.

Transcriptome analysis identified 46 differentially expressed genes affected by DQJD treatment.

Activation of the RXR-γ/PPAR-γ/VEGF-α pathway was confirmed as a key mechanism for DQJD's effects.

Abstract

Daqinjiao decoction (DQJD), an ancient traditional Chinese medicine formula, is clinically used in the treatment of cerebral small vessel disease (CSVD). However, the underlying molecular mechanisms by which DQJD exerts its therapeutic effects on CSVD remain elusive. A Sprague Dawley rat model of chronic cerebral hypoperfusion (CCH) was established using bilateral common carotid artery occlusion (BCCAO) surgery. The effects of DQJD administered via intragastric gavage (i.g.) were evaluated by magnetic resonance imaging (MRI), haematoxylin eosin (HE) staining, and transmission electron microscopy. A combined strategy of transcriptomics and network pharmacology was innovatively applied to study the active ingredients, gene targets, and mechanisms of DQJD in treating CSVD. Molecular docking, real‐time quantitative polymerase chain reaction (RT‐qPCR), and Western blot analysis were applied to confirm the above results further. DQJD improved the pathological damage in cortical and hippocampal tissue by reducing the release of inflammatory factors in CCH rats. RNA‐seq technology identified 46 DEGs between DQJD treatment and the model group. Network pharmacology and pathway analysis of DEGs revealed that the PPAR/VEGF signalling pathway was predicted to be significantly affected. Consistently, validation experiments confirmed that activation of the RXR‐γ/PPAR‐γ/VEGF‐α signalling pathway represents a key mechanism underlying DQJD's therapeutic effects against CSVD. DQJD dampened inflammation and ameliorated pathological damage in the hippocampus and cortex, and these beneficial effects were associated with neurovascular protection via activating the RXR‐γ/PPAR‐γ/VEGF‐α pathway.

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