This study evaluated the hair growth-promoting potential of Polygonum cuspidatum aqueous extract (PCAE) in human hair follicle dermal papilla cells (HFDPCs). Six plant-derived extracts were screened using an MTT assay, with Justicia procumbens aqueous extract as a positive control. PCAE was selected as the main candidate because it significantly enhanced HFDPC proliferation and showed the strongest activity. Among the P. cuspidatum extracts prepared with water, 50% ethanol, and 70% ethanol, the aqueous extract displayed the broadest effective concentration range without apparent cytotoxicity and was used for mechanistic analyses. PCAE significantly promoted HFDPC proliferation at 50–300 μg/mL and maintained cell viability even at 400 μg/mL. Western blot analysis showed that PCAE increased Akt phosphorylation in a concentration-dependent manner while decreasing β-catenin protein expression. DKK1 mRNA was strongly up-regulated by PCAE, consistent with the observed decrease in β-catenin. RT-qPCR analysis further showed robust induction of FGF7 mRNA, significant induction of VEGF at selected concentrations, and marked down-regulation of IGF-1. These findings suggest that PCAE enhances HFDPC proliferation in association with Akt phosphorylation and selective regulation of hair growth-related paracrine factors. PCAE may be a potential natural material for hair loss prevention and hair growth promotion.

Abstract
I. Introduction
II. Materials and Methods
    1. Plant materials and preparation of extracts
    2. Cell culture
    3. Cell proliferation assay
    4. Western blot analysis
    5. Quantitative real-time PCR (RT-qPCR)
    6. Statistical analysis
III. Results and Discussion
    1. Screening of plant-derived extracts for HFDPCproliferation-promoting activity
    2. Dose-dependent effects of P. cuspidatum extractson HFDPC proliferation
    3. PCAE activates Akt signaling and reduces β-cateninprotein abundance
    4. PCAE selectively remodels the expression profile ofhair growth-related paracrine factors
IV. Summary and Conclusion
Acknowledgments
Conflict of Interest
Data Availability Statement
Ethics Statement
References

• 서효덕(한국식품연구원 노화연구단) | Hyo-Deok Seo (Aging Research Group, Korea Food Research Institute) Corresponding author
• 양남교(한국식품연구원 노화연구단, 전남대학교 융합식품바이오공학과) | Namgyo Yang (Aging Research Group, Korea Food Research Institute, Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University)
• 이영서(한국식품연구원 노화연구단, 전남대학교 융합식품바이오공학과) | Yeong-Seo Lee (Aging Research Group, Korea Food Research Institute, Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University)