| ORIGINAL ARTICLES |
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Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression |
| Xinxin Li1,2,3, Runlu Shi4, Lingchen Yan1, Weiwei Chu1,2, Ruishuang Sun5, Binkai Zheng1, Shuai Wang1,6, Hui Tan3, Xusheng Wang1, Ying Gao1,2,7 |
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 |
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Abstract Norepinephrine (NA), a stress hormone, can accelerate hair graying by binding to β2 adrenergic receptors (β2AR) on melanocyte stem cells (McSCs). From this, NA-β2AR axis could be a potential target for preventing the stress effect. However, identifying selective blockers for β2AR 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 β2AR, as verified by molecular docking and dynamic simulation assays. When administered to cells, rhynchophylline effectively inhibited NA-β2AR 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 β2AR, thus offering a promising solution for preventing stress-induced hair graying.
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| Keywords
Natural product
Rhynchophylline
Stress
Hair graying
β2 adrenergic signaling
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| Fund:This work was supported by 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). |
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Corresponding Authors:
Hui Tan,E-mail:huitan@email.szu.edu.cn;Xusheng Wang,E-mail:wangxsh27@mail.sysu.edu.cn;Ying Gao,E-mail:gying1008@126.com
E-mail: huitan@email.szu.edu.cn;wangxsh27@mail.sysu.edu.cn;gying1008@126.com
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Issue Date: 26 December 2023
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