Decoding Cholesterol Metabolic Regulation by Naotai Formula in Stroke Management: An Integrated Network Pharmacology...

Area of Science:

• Integrative bioinformatics
• Pharmacology
• Genetics

Background:

• Naotai formula (NTF) is used for stroke, but its molecular mechanisms are unclear.
• Understanding NTF's role in vascular and metabolic regulation is crucial for stroke treatment.

Purpose of the Study:

• To elucidate the molecular targets and pathways of Naotai formula (NTF) in stroke treatment.
• To combine network pharmacology and Mendelian randomization for a comprehensive analysis.
• To identify genetically supported therapeutic targets of NTF for stroke.

Main Methods:

• Network pharmacology (NP) and Summary-data-based Mendelian randomization (SMR) were employed.
• Genome-wide association study (GWAS) data were integrated with expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) data.
• Protein-protein interaction (PPI) networks, drug-compound-target networks, and molecular docking were utilized.

Main Results:

• 579 overlapping genes linked NTF and stroke.
• 44 stroke-associated genes were identified via SMR, including vascular endothelial growth factor A, angiotensinogen (AGT), and lipoprotein(a).
• Key targets like Adiponectin (ADIPOQ), Scavenger Receptor Class B Member 1 (SCARB1), and AGT were identified, with Calycosin showing strong binding to AGT.

Conclusions:

• NTF likely mitigates stroke by modulating genes involved in cholesterol metabolism and vascular regulation.
• The Calycosin-AGT interaction suggests a role in renin-angiotensin system modulation.
• This study provides genetic and mechanistic insights into NTF's therapeutic efficacy for stroke.