Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression

doi:10.1007/s13659-023-00421-z

Natural Products and Bioprospecting ›› 2023, Vol. 13 ›› Issue (6): 54-54.DOI: 10.1007/s13659-023-00421-z

• ORIGINAL ARTICLES • Previous Articles Next Articles

Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression

Xinxin Li^1,2,3, Runlu Shi⁴, Lingchen Yan¹, Weiwei Chu^1,2, Ruishuang Sun⁵, Binkai Zheng¹, Shuai Wang^1,6, Hui Tan³, Xusheng Wang¹, Ying Gao^1,2,7

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

Received:2023-10-24 Online:2023-12-26 Published:2023-12-24
Contact: 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
Supported by:
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).

Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression

Xinxin Li^1,2,3, Runlu Shi⁴, Lingchen Yan¹, Weiwei Chu^1,2, Ruishuang Sun⁵, Binkai Zheng¹, Shuai Wang^1,6, Hui Tan³, Xusheng Wang¹, Ying Gao^1,2,7

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

通讯作者: 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
基金资助:
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).

Abstract

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.

Key words: Natural product, Rhynchophylline, Stress, Hair graying, β2 adrenergic signaling

摘要： 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.

关键词: Natural product, Rhynchophylline, Stress, Hair graying, β2 adrenergic signaling

Xinxin Li, Runlu Shi, Lingchen Yan, Weiwei Chu, Ruishuang Sun, Binkai Zheng, Shuai Wang, Hui Tan, Xusheng Wang, Ying Gao. Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression[J]. Natural Products and Bioprospecting, 2023, 13(6): 54-54.

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Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression

Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression

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