Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-12-01
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| Series: | Natural Products and Bioprospecting |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s13659-023-00421-z |
| _version_ | 1797413690802176000 |
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| author | Xinxin Li Runlu Shi Lingchen Yan Weiwei Chu Ruishuang Sun Binkai Zheng Shuai Wang Hui Tan Xusheng Wang Ying Gao |
| author_facet | Xinxin Li Runlu Shi Lingchen Yan Weiwei Chu Ruishuang Sun Binkai Zheng Shuai Wang Hui Tan Xusheng Wang Ying Gao |
| author_sort | Xinxin Li |
| collection | DOAJ |
| description | 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. Graphical Abstract |
| first_indexed | 2024-03-09T05:21:36Z |
| format | Article |
| id | doaj.art-cd374ed6f1fc4c30a5a8c09ca2fcfb17 |
| institution | Directory Open Access Journal |
| issn | 2192-2195 2192-2209 |
| language | English |
| last_indexed | 2024-03-09T05:21:36Z |
| publishDate | 2023-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Natural Products and Bioprospecting |
| spelling | doaj.art-cd374ed6f1fc4c30a5a8c09ca2fcfb172023-12-03T12:40:25ZengSpringerOpenNatural Products and Bioprospecting2192-21952192-22092023-12-0113111610.1007/s13659-023-00421-zNatural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppressionXinxin Li0Runlu Shi1Lingchen Yan2Weiwei Chu3Ruishuang Sun4Binkai Zheng5Shuai Wang6Hui Tan7Xusheng Wang8Ying Gao9School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen UniversityInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua UniversitySchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen UniversitySchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen UniversityDepartment of Plastic and Reconstructive Surgery, Guangdong Second Provincial General HospitalSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen UniversitySchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen UniversityCenter for Child Care and Mental Health, Shenzhen Children’s Hospital Affiliated to Shantou University Medical CollegeSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen UniversitySchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen UniversityAbstract 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. Graphical Abstracthttps://doi.org/10.1007/s13659-023-00421-zNatural productRhynchophyllineStressHair grayingβ2 adrenergic signaling |
| spellingShingle | 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 Natural Products and Bioprospecting Natural product Rhynchophylline Stress Hair graying β2 adrenergic signaling |
| title | Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression |
| title_full | Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression |
| title_fullStr | Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression |
| title_full_unstemmed | Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression |
| title_short | Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression |
| title_sort | natural product rhynchophylline prevents stress induced hair graying by preserving melanocyte stem cells via the β2 adrenergic pathway suppression |
| topic | Natural product Rhynchophylline Stress Hair graying β2 adrenergic signaling |
| url | https://doi.org/10.1007/s13659-023-00421-z |
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