Large-Scale Evaluation of Traditional Chinese Medicines Reveals Potential PPARγ Modulators for Type 2 Diabetes...

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a pivotal nuclear receptor regulating glucose and lipid homeostasis, making it a primary therapeutic target for type 2 diabetes mellitus (T2DM). Despite the therapeutic potential of Traditional Chinese Medicine (TCM), a systematic, large-scale evaluation of its modulatory effects on PPARγ remains insufficient.

We developed a high-throughput screening platform utilizing a pGL4.17-PPARγ promoter-luciferase reporter system in 293 T cells. A library of 639 TCM samples (345 single formulas, SF; 294 multiple formulas, MF) was evaluated. Leading candidates were validated through RT-qPCR, Western blotting, and ELISA to assess PPARγ mRNA expression and protein abundance.

Screening identified 139 TCMs that enhanced PPARγ activity, with 47 SF and 2 MF achieving an effective rate (ER) exceeding 60%. Notably, 25 of these are novel candidates for T2D, while 24 align with previous reports. Specifically, Astragali Radix (S241) and Puerariae Thomsonii Radix (S258) were identified as potent inducers, significantly upregulating PPARγ at both transcriptional and translational levels. Conversely, 55 samples, including Gymnema sylvestre (S169) and Paris polyphylla (S3), exhibited robust inhibitory effects, reducing ER by -52% to -99%.

This study identified 45 novel TCM candidates for T2D management. While several TCMs demonstrated PPARγ inhibition despite their traditional use for diabetic symptom alleviation, our findings suggest that a comprehensive evaluation is essential to balance their immediate clinical benefits with long-term metabolic management and potential side effects.