Zhu Mingxi, Fang Yuan, Huang Ying, Qiu Wenshi, Ning Ling, Li Yanan, Zhu Chengwei, Song Xiaoxiong, Wu Yuanyuan, Zou Wei, Wang Aiyun, Lu Yin
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Phytomedicine. 2025 Jul 25;143:156837. doi: 10.1016/j.phymed.2025.156837. Epub 2025 May 12.
As a prevalent type of hair loss, androgenetic alopecia (AGA) is complex due to the interplay of multiple factors, which has led to a long-standing exploration gap in the field of drug treatment. Qu-shi-yu-fa Decoction (QSYF), a traditional prescription, has shown positive effects on AGA in clinical practice, but its exact therapeutic mechanism has not been fully revealed.
This study aimed to elucidate the mechanism of QSYF in the treatment of AGA.
Identification of active components of QSYF using UPLC-MS/MS analysis. An AGA model was established for C57bL/6 mice using dihydrotestosterone to assess the effects of QSYF. Hair growth was observed using dermoscopy. Skin tissues were examined histologically using hematoxylin and eosin (H&E) staining. RNA-seq was performed on mouse skin samples to identify biological processes and targets. Biological processes and targets obtained from RNA-seq analysis were evaluated using Western blotting, RT-PCR and immunofluorescence assays. Mice were treated with target inhibitors and observed for hair growth for reverse validation. Network pharmacology was utilized to identify the key signaling pathways through which the targets functioned, and Western blotting was utilized for validation.
The study identified 43 QSYF components.QSYF promoted hair regeneration and increased hair bulb diameter and skin thickness in AGA mice. Transcriptome analysis showed that hair cycle and keratinization were important biological processes in QSYF treatment of AGA, while QSYF could upregulate the expression of key targets FOXN1 and TGM3. Reverse experiments showed that Inhibition of FOXN1 and TGM3 leads to exacerbation of AGA. Network pharmacological analysis showed that QSYF regulation of hair cycle and keratinization involves activation of PI3K-AKT and MAPK signaling.
This study demonstrates for the first time that QSYF regulates the hair cycle by up-regulating the expression of FOXN1 and promotes keratinization by up-regulating the expression of TGM3, both of them together exerting therapeutic effects on AGA.
雄激素性脱发（AGA）作为一种常见的脱发类型，由于多种因素相互作用而较为复杂，这导致药物治疗领域长期存在探索空白。祛湿育发汤（QSYF）作为一种传统方剂，在临床实践中已显示出对AGA有积极作用，但其确切治疗机制尚未完全阐明。
本研究旨在阐明QSYF治疗AGA的机制。
采用超高效液相色谱-串联质谱（UPLC-MS/MS）分析鉴定QSYF的活性成分。使用二氢睾酮为C57bL/6小鼠建立AGA模型，以评估QSYF的作用。使用皮肤镜观察毛发生长情况。用苏木精-伊红（H&E）染色对皮肤组织进行组织学检查。对小鼠皮肤样本进行RNA测序，以鉴定生物学过程和靶点。使用蛋白质免疫印迹法、逆转录-聚合酶链反应（RT-PCR）和免疫荧光分析评估RNA测序分析获得的生物学过程和靶点。用靶向抑制剂处理小鼠并观察毛发生长情况进行反向验证。利用网络药理学确定靶点发挥作用的关键信号通路，并通过蛋白质免疫印迹法进行验证。
该研究鉴定出43种QSYF成分。QSYF促进AGA小鼠毛发再生，增加毛囊球直径和皮肤厚度。转录组分析表明，毛发周期和角质化是QSYF治疗AGA的重要生物学过程，而QSYF可上调关键靶点叉头框蛋白N1（FOXN1）和转谷氨酰胺酶3（TGM3）的表达。反向实验表明，抑制FOXN1和TGM3会导致AGA加重。网络药理学分析表明，QSYF对毛发周期和角质化的调节涉及磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-AKT）和丝裂原活化蛋白激酶（MAPK）信号的激活。
本研究首次证明，QSYF通过上调FOXN1的表达来调节毛发周期，并通过上调TGM3的表达促进角质化，二者共同对AGA发挥治疗作用。
