Phlegm-dampness constitution in obesity: A systematic review, meta-analysis, and reverse network pharmacology study...

Obesity is heterogeneous, and personalising management requires stratifiers beyond BMI. In Chinese populations, the Phlegm‑Dampness Constitution (PDC) is a clinically defined traditional medicine phenotype consistently overrepresented among adults with obesity, yet its molecular characterisation remains incomplete.

This study seeks to assess the distribution of Traditional Chinese Medicine(TCM) constitutions among obese adults in China and use bioinformatics and network pharmacology to explore the multi-target mechanisms of obesity in the Phlegm-Dampness Constitution.

A meta-analysis identified the core constitution type, followed by integration of GEO gene expression data with obesity-related targets. Key driver genes were identified using the Random Forest algorithm and topological analysis. A reverse network pharmacology approach then predicted potential active compounds and Chinese herbs, which were validated through molecular docking and medicinal property analysis.

The meta-analysis (28 studies) determined PDC as the most common type (prevalence: 19.3%). Bioinformatics identified 52 core targets enriched in lipid metabolism and insulin resistance pathways, highlighting seven key genes (e. g., IKBKB, MTOR). Kaempferol, luteolin, and quercetin were predicted as main active compounds, showing strong binding affinities to key targets. The predicted herbs were primarily warm or cold in nature.

The PDC is a key risk factor for obesity, possibly linked to lipid metabolism issues and inflammation via the CD36/mTOR pathway. The suggested herbal treatments align with strategies to "dry dampness, resolve phlegm, and enhance Qi flow to relieve stagnation," providing a scientific foundation for personalized obesity prevention and management.