Bavachinin (BVC), a prenylated flavonoid from Psoralea corylifolia seeds, is a reported natural PPAR agonist, but its metabolic efficacy and potential skeletal effects are unclear. This study examined the functional actions of BVC across various metabolic, inflammatory, and skeletal systems. BVC moderately activated PPAR, enhanced aP2 expression, and promoted adipogenic differentiation in hMSCs and in a de novo fat pad model. In high-fat diet-induced obese mice, BVC improved glucose tolerance and insulin sensitivity, restored Ser273-dependent PPAR target gene expression, and inhibited PPAR phosphorylation at Ser273 without inducing TZD-like side effects such as fluid retention, cardiac hypertrophy, or ENaC upregulation. BVC also suppressed pro-inflammatory cytokine expression and nitric oxide production in adipocytes, macrophages, and adipose tissue. In contrast to its metabolic benefits, BVC inhibited the osteoblast differentiation of hMSCs and impaired bone regeneration in a rat calvarial defect model. Hence, BVC acts as a selective PPAR modulator with metabolic and anti-inflammatory benefits but has adverse skeletal effects, highlighting its therapeutic potential benefits but noting important safety considerations regarding its use.

Abstract
I. Introduction
II. Materials and Methods
    1. Materials
    2. Adipogenic induction and Oil Red O staining
    3. Osteogenic induction and Alizarin Red S staining
    4. Rodents
    5. RNA extraction and quantitative RT-PCR
    6. Western blotting
    7. De novo fat pad formation
    8. Bone regeneration in rat calvarial defect model
    9. Statistical analysis
III. Results and Discussion
    1. BVC enhances PPARγ activity and adipogenesis
    2. BVC alleviates metabolic disorders in HFD-inducedobese without fluid retention and cardiac dysfunction
    3. BVC ameliorates inflammation
    4. BVC inhibits osteoblast differentiation and boneregeneration
IV. Summary and Conclusion
Acknowledgement
Conflict of Interest
References

• Hyun-Jun Jang(Precision Nutrition Research Group, Korea Food Research Institute)
• Myung-Sunny Kim(Precision Nutrition Research Group, Korea Food Research Institute, Department of Food Biotechnology, University of Science & Technology) Corresponding author