Hesed Bio Corporation, Pohang 37673, Republic of Korea.
Generative Genomics Research Center, Global Green Research & Development Center, Handong Global University, Pohang 37554, Republic of Korea.
Int J Mol Sci. 2024 Oct 7;25(19):10774. 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.
真皮乳头细胞（DPC）位于毛囊底部，在毛发生长、形状和周期中起着关键作用。表皮生长因子受体（EGFR）和 Wnt/β-连环蛋白信号通路对于促进角质形成细胞的激活以及 DPC 中的毛囊形成至关重要。胡椒基酸是一种小分子，可诱导角质形成细胞中 EGFR 的激活。然而，胡椒基酸对 DPC 刺激毛发生长的作用尚未得到研究。在本研究中，胡椒基酸被证明可激活 DPC 中的 Wnt/β-连环蛋白信号通路以及 EGFR 信号通路。胡椒基酸抑制 DKK1 的表达，这可能促进了 β-连环蛋白在核内的积累。此外，胡椒基酸促进细胞生长和细胞周期蛋白 D 的上调，并增加了 DPC 标志物碱性磷酸酶（ALP）的表达。在一项临床研究中，使用含有胡椒基酸制剂的组与安慰剂组相比，单位面积的毛发数量显著增加。这些结果表明胡椒基酸是一种有前途的脱发治疗新候选药物。
