Efficacy of derinat as a treatment for murine and androgenetic alopecia (AGA) patients

Ching-Ying Wu, Wei-Chiao Chen, Cheng-Hsu Hsieh, Yun-Fang Liang, Wei-Ju Li, Hao Shen, Wei-Yen Wei, Ting-Yu Chou, Yen-Chun Chiu, Hao Huang, Wen-Li Hsu
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Abstract

Abstract Background Androgenetic alopecia (AGA), one of the most common types of hair loss, is associated with oxidative stress, inflammation and aging. Derinat, a transient receptor potential canonical channels (TRPCs) inhibitor, restrains TRPCs-mediated increase intracellular Ca 2+ signaling, which initiates the skin aging process with intracellular reactive oxygen species (ROS) accumulation. This study investigated whether Derinat protected skin from oxidative stress-induced damage and aging, thus inhibiting AGA pathogenesis. Methods The lifespan of Caenorhabditis elegans was measured to examine the capacity of Derinat to oppose the oxidative stress induced-aging process, which drives the hair cycle from anagen to catagen phase. The experiments that used BALB/c-nu and C57BL/6 mice determined the effects of Derinat on hair cycle and oxidative stress in skin. To further apply Derinat to clinical study, the resulting relationship between AGA pathogenesis and TRPCs-regulated oxidative stress was confirmed using the bioinformatics approach. We consequently used the parameters of hair density, hair diameter, hair recovery and quality of life index to evaluate the effect of Derinat treatment on AGA subjects. Results Derinat restrained the oxidative stress induced-aging process sufficiently to extend the lifespan of worms. Derinat also changed the hair growth patterns of mice by maintenance of the hair cycle at the anagen phase. This efficacy was due to reduction of TRPCs-mediated ROS accumulation. Because the bioinformatics analysis found that AGA pathogenesis is associated with TRPCs-regulated oxidative stress and inflammation, treatment with Derinat in AGA subjects increased positive outcomes of oral medication while mitigating the impairment of AGA subjects’ quality of life. Conclusions Derinat restrains AGA pathogenesis and may provide a new therapeutic approach for treating AGA. ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov , date of registration 07/11/2022. Trial registration ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov , date of registration 07/11/2022
derinat治疗小鼠和雄激素性脱发(AGA)患者的疗效
背景雄激素性脱发(AGA)是最常见的脱发类型之一,与氧化应激、炎症和衰老有关。Derinat是一种瞬时受体电位规范通道(trpc)抑制剂,可抑制trpc介导的细胞内ca2 +信号的增加,ca2 +信号通过细胞内活性氧(ROS)的积累启动皮肤衰老过程。本研究探讨了Derinat是否能保护皮肤免受氧化应激诱导的损伤和衰老,从而抑制AGA的发病机制。方法测定秀丽隐杆线虫的寿命,研究其抗氧化应激诱导的衰老过程的能力。氧化应激诱导的衰老过程驱动毛发从生长期到衰退期的循环。以BALB/c-nu和C57BL/6小鼠为实验对象,研究了Derinat对毛发周期和皮肤氧化应激的影响。为了进一步将Derinat应用于临床研究,我们利用生物信息学方法证实了AGA发病机制与trpc调控的氧化应激之间的关系。因此,我们使用头发密度、头发直径、头发恢复和生活质量指数等参数来评估Derinat治疗对AGA受试者的效果。结果derinate能有效抑制氧化应激诱导的衰老过程,延长线虫的寿命。Derinat还通过维持毛发生长周期来改变小鼠毛发生长模式。这种功效是由于trpc介导的ROS积累减少。由于生物信息学分析发现AGA发病机制与trpc调节的氧化应激和炎症有关,因此在AGA受试者中使用Derinat治疗增加了口服药物的阳性结果,同时减轻了AGA受试者生活质量的损害。结论derinine抑制了AGA的发病机制,为AGA的治疗提供了新的途径。ClinicalTrials.gov标识符NCT05450861, https://register.clinicaltrials.gov,注册日期07/11/2022。临床试验注册ClinicalTrials.gov标识符NCT05450861, https://register.clinicaltrials.gov,注册日期07/11/2022
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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