关键词: Androgenic alopecia Dermal papilla cells Ellagic acid Ferroptosis β-catenin

Mesh : Animals Male Mice Alopecia / drug therapy chemically induced beta Catenin / metabolism Dihydrotestosterone / pharmacology Ellagic Acid / pharmacology Ferroptosis / drug effects Hair / drug effects growth & development Mice, Inbred C57BL Regeneration / drug effects Wnt Signaling Pathway / drug effects

来  源:   DOI:10.1016/j.jep.2024.118227

Abstract:
BACKGROUND: Androgenic alopecia (AGA) is the most prevalent form of hair loss in clinical practice and affects the physical and psychological well-being of adolescents. Paeonia lactiflora Pallas (PL), which is widely used in traditional Chinese medicine, enhances blood function and promotes hair growth, and ellagic acid (EA), a polyphenol in PL extract, shows strong antioxidant, anti-aging, and anti-inflammatory properties and also plays a role in the treatment of various skin conditions. However, its role and mechanism of action in AGA remain unclear.
OBJECTIVE: To determine whether EA can rescue slow hair regeneration by regulating dihydrotestosterone (DHT)-induced ferroptosis in AGA mice and clarify the effect of EA on DHT-induced ferroptosis in dermal papilla cells (DPCs).
METHODS: Male C57BL/6 mice were used to establish a DHT-induced AGA mouse model, whereas DPCs were used to establish a DHT-induced cellular model. Thereafter, we investigated the therapeutic mechanism of action of EA via immunofluorescence, western blot analysis, immunohistochemistry, electron microscopy, and molecular docking.
RESULTS: EA stimulated hair regeneration in mice and reversed DHT-induced increases in iron content, lipid peroxidation, and DHT-induced mitochondrial dysfunction by activating the Wnt/β-catenin signaling pathway. Further, β-catenin knockdown suppressed the inhibitory effect of EA on DHT-induced ferroptosis in DPCs.
CONCLUSIONS: EA inhibits DHT-induced ferroptosis and promotes hair regrowth in mice by activating the Wnt/β-catenin signaling pathway. Thus, it has potential for use as a treatment option for AGA.
摘要:
背景:雄激素性脱发(AGA)是临床实践中最普遍的脱发形式,会影响青少年的身心健康。白芍(PL),广泛用于中药,增强血液功能,促进头发生长,和鞣花酸(EA),PL提取物中的多酚,显示强抗氧化剂,抗衰老,和抗炎特性,并在各种皮肤状况的治疗中发挥作用。然而,其在AGA中的作用和作用机制尚不清楚。
目的:观察电针是否能通过调节二氢睾酮(DHT)诱导的AGA小鼠的铁凋亡来挽救缓慢的毛发再生,并阐明电针对DHT诱导的毛乳头细胞(DPCs)铁凋亡的影响。
方法:用雄性C57BL/6小鼠建立DHT诱导的AGA小鼠模型,而DPC用于建立DHT诱导的细胞模型。此后,我们通过免疫荧光研究了EA的治疗作用机制,蛋白质印迹分析,免疫组织化学,电子显微镜,和分子对接。
结果:EA刺激小鼠毛发再生,逆转DHT诱导的铁含量增加,脂质过氧化,和DHT通过激活Wnt/β-catenin信号通路诱导线粒体功能障碍。Further,β-catenin敲低抑制EA对DHT诱导的DPC中的铁凋亡的抑制作用。
结论:EA通过激活Wnt/β-catenin信号通路抑制DHT诱导的小鼠铁凋亡并促进毛发再生。因此,它有可能用作AGA的治疗选择。
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