Manzoor Majid, Chen Danni, Lin Jiahui, Wang Ying, Xiang Lan, Qi Jianhua
College of Pharmaceutical Science, Zhejiang University, 866 Yu Hang Road, Hangzhou, China.
College of Pharmaceutical Science, Zhejiang University, 866 Yu Hang Road, Hangzhou, China.
Phytomedicine. 2025 Jan;136:156289. doi: 10.1016/j.phymed.2024.156289. Epub 2024 Nov 26.
Hair follicles play a crucial role in hair growth, wound healing, thermoregulation, and sebum production. Hair loss affects millions of people worldwide, yet therapeutic options for managing hair loss and pattern baldness are limited. Isoquercitrin (IQ), a natural small molecule from drinkable Chinese tea, is famous for anti-aging properties.
This study aimed to explore the potential of IQ in treating and preventing hair loss, along with its underlying mechanisms.
The adult male and female, as well as middle-aged female sprague dawley (SD) rats were used to conduct hair growth experiments in vivo. Signaling pathways and target protein identification were analyzed through western blotting, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) analyses. Further, the targets were confirmed through in vivo inhibition experiments.
IQ is reported here to stimulate anagen phase initiation and hair regrowth by directly interacting with adenosine 5'-monophosphate-activated protein kinase (AMPK) and insulin-like growth factor 1 receptor (IGF-1R). This process involves the AMPK/mammalian target of rapamycin (mTOR)/ unc-51-like autophagy-activating kinase 1 (ULK1) signalling pathway to trigger autophagy and the IGF-1R/phosphatidylinositol 3-kinase (PI3 K)/protein Kinase B (AKT), vascular endothelial growth factor (VEGF)/ vascular endothelial growth factor receptor (VEGFR)/ angiotensin (ANG) pathways to promote angiogenesis in female rats. Furthermore, the hair regrowth efficacy of IQ in adult male rats and middle-aged female rats was verified and shown. Similarly, our findings indicate that IQ promotes hair regrowth in middle-aged rats through autophagy and angiogenesis, akin to its effects in adult rats.
AMPK and IGF-1R proteins are identified as the target proteins of IQ and the AMPK/mTOR/ULK1, IGF-1R/PI3K/AKT and VEGF/VEGFR/ANG signalling pathways take important roles in hair growth effect of IQ. Thus, these signaling pathways are crucial for developing future treatments and clinical strategies for hair regeneration.
毛囊在头发生长、伤口愈合、体温调节和皮脂分泌中起关键作用。脱发影响着全球数百万人，然而治疗脱发和斑秃的选择有限。异槲皮苷（IQ）是一种来自可饮用中国茶的天然小分子，以其抗衰老特性而闻名。
本研究旨在探索异槲皮苷在治疗和预防脱发方面的潜力及其潜在机制。
使用成年雄性和雌性以及中年雌性Sprague Dawley（SD）大鼠进行体内毛发生长实验。通过蛋白质免疫印迹法、药物亲和力响应靶点稳定性（DARTS）、细胞热位移分析（CETSA）和表面等离子体共振（SPR）分析来分析信号通路和靶蛋白鉴定。此外，通过体内抑制实验来确认靶点。
本文报道异槲皮苷通过直接与5'-单磷酸腺苷激活蛋白激酶（AMPK）和胰岛素样生长因子1受体（IGF-1R）相互作用来刺激生长期开始和毛发再生。这个过程涉及AMPK/雷帕霉素靶蛋白（mTOR）/unc-51样自噬激活激酶1（ULK1）信号通路来触发自噬，以及IGF-1R/磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）、血管内皮生长因子（VEGF）/血管内皮生长因子受体（VEGFR）/血管紧张素（ANG）通路来促进雌性大鼠的血管生成。此外，还验证并展示了异槲皮苷在成年雄性大鼠和中年雌性大鼠中的毛发再生效果。同样，我们的研究结果表明，异槲皮苷通过自噬和血管生成促进中年大鼠的毛发再生，类似于其在成年大鼠中的作用。
AMPK和IGF-1R蛋白被确定为异槲皮苷的靶蛋白，并且AMPK/mTOR/ULK1、IGF-1R/PI3K/AKT和VEGF/VEGFR/ANG信号通路在异槲皮苷的毛发生长作用中起重要作用。因此，这些信号通路对于开发未来的毛发再生治疗方法和临床策略至关重要。
