最多等待 10 秒，若超时请稍后重试。
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China.
Department of Anesthesiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
Nat Prod Bioprospect. 2023 Dec 1;13(1):54. doi: 10.1007/s13659-023-00421-z.
Norepinephrine (NA), a stress hormone, can accelerate hair graying by binding to β2 adrenergic receptors (βAR) on melanocyte stem cells (McSCs). From this, NA-βAR axis could be a potential target for preventing the stress effect. However, identifying selective blockers for βAR has been a key challenge. Therefore, in this study, advanced computer-aided drug design (CADD) techniques were harnessed to screen natural molecules, leading to the discovery of rhynchophylline as a promising compound. Rhynchophylline exhibited strong and stable binding within the active site of βAR, as verified by molecular docking and dynamic simulation assays. When administered to cells, rhynchophylline effectively inhibited NA-βAR signaling. This intervention resulted in a significant reduction of hair graying in a stress-induced mouse model, from 28.5% to 8.2%. To gain a deeper understanding of the underlying mechanisms, transcriptome sequencing was employed, which revealed that NA might disrupt melanogenesis by affecting intracellular calcium balance and promoting cell apoptosis. Importantly, rhynchophylline acted as a potent inhibitor of these downstream pathways. In conclusion, the study demonstrated that rhynchophylline has the potential to mitigate the negative impact of NA on melanogenesis by targeting βAR, thus offering a promising solution for preventing stress-induced hair graying.
去甲肾上腺素（NA）作为一种应激激素，可通过与黑素细胞干细胞（McSCs）上的β2肾上腺素能受体（βAR）结合来加速头发变白。据此，NA-βAR轴可能是预防应激效应的一个潜在靶点。然而，识别βAR的选择性阻滞剂一直是一项关键挑战。因此，在本研究中，利用先进的计算机辅助药物设计（CADD）技术筛选天然分子，从而发现钩藤碱是一种有前景的化合物。通过分子对接和动态模拟试验验证，钩藤碱在βAR的活性位点内表现出强烈且稳定的结合。当应用于细胞时，钩藤碱有效抑制了NA-βAR信号传导。在应激诱导的小鼠模型中，这种干预使头发变白显著减少，从28.5%降至8.2%。为了更深入地了解潜在机制，采用了转录组测序，结果显示NA可能通过影响细胞内钙平衡和促进细胞凋亡来破坏黑色素生成。重要的是，钩藤碱是这些下游途径的有效抑制剂。总之，该研究表明钩藤碱有可能通过靶向βAR减轻NA对黑色素生成的负面影响，从而为预防应激诱导的头发变白提供了一个有前景的解决方案。
