Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via theβ2 adrenergic pathway suppression  

作　　者：Xinxin Li Runlu Shi Lingchen Yan Weiwei Chu Ruishuang Sun Binkai Zheng Shuai Wang Hui Tan Xusheng Wang Ying Gao 

机构地区：[1]School of Pharmaceutical Sciences(Shenzhen),Sun Yat-sen University,Shenzhen 518107,China [2]Department of Anesthesiology,The First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,China [3]Center for Child Care and Mental Health,Shenzhen Children’s Hospital Affiliated to Shantou University Medical College,Shenzhen 518026,China [4]Institute of Biopharmaceutical and Health Engineering,Tsinghua Shenzhen International Graduate School,Tsinghua University,Shenzhen 518055,China [5]Department of Plastic and Reconstructive Surgery,Guangdong Second Provincial General Hospital,Guangzhou 510317,China [6]The Yonghe Medical Beauty Clinic Department,Guangzhou 510630,China [7]Department of Anesthesiology,The First People’s Hospital of Foshan,Foshan 528000,China

出　　处：《Natural Products and Bioprospecting》2023年第1期14-29,共16页应用天然产物（英文）

基　　金：the Shenzhen Science and Technology Innovation Committee(grant numbers JCYJ20200109142444449,JCYJ20210324120007021);the National Natural Science Foundation of China(grant numbers 31801196);Basic and Applied Basic Research Foundation of Guangdong Province(grant numbers 2022A1515110645).

摘　　要：Norepinephrine(NA),a stress hormone,can accelerate hair graying by binding toβ2 adrenergic receptors(β_(2)AR)on melanocyte stem cells(McSCs).From this,NA-β_(2)AR axis could be a potential target for preventing the stress effect.However,identifying selective blockers forβ_(2)AR 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 ofβ_(2)AR,as verified by molecular docking and dynamic simulation assays.When administered to cells,rhyncho-phylline effectively inhibited NA-β_(2)AR 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 targetingβ_(2)AR,thus offering a promising solution for preventing stress-induced hair graying.

关 键 词：Natural product RHYNCHOPHYLLINE STRESS Hair graying β2 adrenergic signaling 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]