Piperonylic Acid Promotes Hair Growth by Activation of EGFR and Wnt/β-Catenin Pathway

• Published in: International journal of molecular sciences Vol. 25; no. 19; p. 10774
• Main Authors: Han, Seung Hyun, Jo, Kyung Won, Kim, Younghyun, Kim, Kyong-Tai
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2024; MDPI
• Subjects: Acids; Adult; Alkaline Phosphatase - metabolism; Androgens; Animals; beta Catenin - metabolism; Cell adhesion molecules; Cell cycle; Cell growth; Cell Proliferation - drug effects; EGFR; Epidermal growth factor; ErbB Receptors - metabolism; Female; Follicles; Growth; Hair; Hair - drug effects; Hair - growth & development; Hair - metabolism; Hair Follicle - drug effects; Hair Follicle - growth & development; Hair Follicle - metabolism; hair growth; Hair loss; Health aspects; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Keratinocytes - drug effects; Keratinocytes - metabolism; Kinases; Male; Mice; Natural products; Organic compounds; Phosphatase; Phosphorylation; piperonylic acid; Proteins; Wnt proteins; Wnt Signaling Pathway - drug effects; Wnt/β-catenin; Wound healing; South Korea; hair growth; Wnt/β-catenin; EGFR; piperonylic acid
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251910774

Dermal papilla cells (DPCs) are located at the bottom of the hair follicle and play a critical role in hair growth, shape, and cycle. Epidermal growth factor receptor (EGFR) and Wnt/β-catenin signaling pathways are essential in promoting keratinocyte activation as well as hair follicle formation in DPCs. Piperonylic acid is a small molecule that induces EGFR activation in keratinocytes. However, the effects of piperonylic acid on DPCs in regard to the stimulation of hair growth have not been studied. In the present study, piperonylic acid was shown to activate the Wnt/β-catenin signaling pathway in addition to the EGFR signaling pathway in DPCs. Piperonylic acid suppressed DKK1 expression, which presumably promoted the accumulation of β-catenin in the nucleus. In addition, piperonylic acid promoted cyclin D upregulation and cell growth and increased the expression of alkaline phosphatase (ALP), a DPC marker. In a clinical study, the group that applied a formulation containing piperonylic acid had a significantly higher number of hairs per unit area than the placebo group. These results identify piperonylic acid as a promising new candidate for hair loss treatment.