关键词: 1,3,6-tri-O-galloylglucose (TGG) Androgen-SRD5A2-AR axis Androgenetic alopecia Camellia oleifera seed shell polyphenols (CSSP) Molecular docking Wnt/β-catenin pathway

Mesh : Alopecia / drug therapy Camellia / chemistry Animals Mice Polyphenols / pharmacology isolation & purification Seeds / chemistry Molecular Docking Simulation Wnt Signaling Pathway / drug effects Male 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism Mice, Inbred C57BL Disease Models, Animal Molecular Structure Hydrolyzable Tannins / pharmacology isolation & purification

来  源:   DOI:10.1016/j.fitote.2024.106116

Abstract:
Androgenetic alopecia (AGA) is the leading cause of hair loss in adults. Its pathogenesis remains unclear, but studies have shown that the androgen-mediated 5α-reductase-AR receptor pathway and the Wnt/β-catenin signaling pathway play significant roles. Camellia oleifera is an oil plant, and its fruits have been documented in folklore as having a hair cleansing effect and preventing hair loss. In this study, we used UPLC-Q-TOF-MS/MS to identify the structure of the substances contained in the polyphenols of Camellia oleifera seed shell. These polyphenols are mainly used for shampooing and anti-hair loss purposes. Next, we used molecular docking technology to dock 41 polyphenols and steroidal 5 alpha reductase 2 (SRD5A2). We found that the docking scores and docking sites of 1,3,6-tri-O-galloylglucose (TGG) and finasteride were similar. We constructed a mouse model of DHT-induced AGA to evaluate the effects of Camellia oleifera seed shell polyphenols (CSSP) and TGG in vivo. Treatment with CSSP and TGG alleviated alopecia symptoms and reduced DHT levels. Additionally, CSSP and TGG were able to reduce androgen levels by inhibiting the SRD5A2-AR receptor signaling pathway. Furthermore, by regulating the secretion of growth factors and activating the Wnt/β-catenin signaling pathway, CSSP and TGG were able to extend the duration of hair growth. In conclusion, our study showed that CSSP and TGG can improve AGA in C57BL/6 J mice and reduce the effect of androgen on hair follicle through the two signaling pathways mentioned above. This provides new insights into the material basis and mechanism of the treatment of AGA by CSSP.
摘要:
雄激素性脱发(AGA)是成人脱发的主要原因。其发病机制尚不清楚,但研究表明,雄激素介导的5α-还原酶-AR受体通路和Wnt/β-catenin信号通路发挥了重要作用。油茶是一种油料植物,它的果实在民间传说中被证明具有清洁头发和防止脱发的作用。在这项研究中,利用UPLC-Q-TOF-MS/MS对油茶种壳多酚中的物质进行结构鉴定。这些多酚主要用于洗发和抗脱发的目的。接下来,我们使用分子对接技术对接41种多酚和甾体5α还原酶2(SRD5A2)。我们发现,1,3,6-三-O-谷酰葡萄糖(TGG)和非那雄胺的对接得分和对接位点相似。我们构建了DHT诱导的AGA小鼠模型,以评估油茶种子壳多酚(CSSP)和TGG在体内的作用。用CSSP和TGG治疗减轻了脱发症状并降低了DHT水平。此外,CSSP和TGG能够通过抑制SRD5A2-AR受体信号通路来降低雄激素水平。此外,通过调节生长因子的分泌和激活Wnt/β-catenin信号通路,CSSP和TGG能够延长毛发生长的持续时间。总之,我们的研究表明,CSSP和TGG可以通过上述两种信号通路改善C57BL/6J小鼠的AGA,并降低雄激素对毛囊的影响。这为CSSP治疗AGA的物质基础和机制提供了新的见解。
公众号