Park Kkotnara, Youn Isoo, Suh Jung Min, Choi Min Hye, Bae Da-Woon, Park Soo-Bong, Kwack Mi Hee, Cha Sun-Shin, Jang Dae Sik, Sung Young Kwan, Bae Yun Soo, Seo Eun Kyoung
Department of Life Sciences, Ewha Womans University, Seoul 03760, Republic of Korea.
College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea.
Molecules. 2025 May 21;30(10):2246. doi: 10.3390/molecules30102246.
Androgenetic alopecia is associated with testosterone-mediated anagen-to-catagen transition and matrix keratinocyte apoptosis in hair follicle cells. Activation of Nox isozymes is involved in testosterone-mediated keratinocyte apoptosis, leading to androgenetic alopecia. This indicates that Nox isozymes can serve as therapeutic targets for androgenetic alopecia. The isolated compounds from natural products were screened to evaluate their ROS-inhibition efficacy and it was found that 1'-1'-acetoxychavicol acetate (ACA, ), a natural compound isolated from (L.) Willd. (Zingiberaceae), exhibits inhibitory activity on Nox isozymes. Nox inhibition by ACA suppressed testosterone-dependent HO generation and cell death in keratinocytes. Incubation with ACA in human hair follicle organ culture mitigated testosterone-dependent suppression of hair growth. We validated that ACA regulates androgenetic alopecia in a mouse model. Local application of ACA on the dorsal skin in an androgenetic alopecia model of C57BL/6 mice significantly suppressed testosterone-induced hair loss in a dose-dependent manner. Moreover, hair follicle length in ACA-treated mice was enhanced compared to that in control mice. These findings provide a molecular mechanism in which ACA inhibits Nox activity in hair follicle cells, indicating its potential as an effective treatment of AGA.
雄激素性脱发与睾酮介导的毛囊细胞从生长期到退行期的转变以及毛基质角质形成细胞凋亡有关。Nox 同工酶的激活参与了睾酮介导的角质形成细胞凋亡，从而导致雄激素性脱发。这表明 Nox 同工酶可作为雄激素性脱发的治疗靶点。对从天然产物中分离出的化合物进行筛选，以评估其对活性氧的抑制功效，结果发现从姜科植物高良姜中分离出的天然化合物乙酸 1'-乙酰氧基胡椒酚酯（ACA）对 Nox 同工酶具有抑制活性。ACA 对 Nox 的抑制作用可抑制睾酮依赖性的角质形成细胞中过氧化氢的产生和细胞死亡。在人毛囊器官培养中用 ACA 孵育可减轻睾酮对毛发生长的依赖性抑制。我们在小鼠模型中验证了 ACA 对雄激素性脱发的调节作用。在 C57BL/6 小鼠雄激素性脱发模型的背部皮肤局部应用 ACA 可显著剂量依赖性地抑制睾酮诱导的脱发。此外，与对照小鼠相比，经 ACA 处理的小鼠毛囊长度增加。这些发现提供了一种分子机制，即 ACA 抑制毛囊细胞中的 Nox 活性，表明其作为雄激素性脱发有效治疗方法的潜力。
