Salidroside inhibits melanin synthesis and melanoma growth via mTOR and PI3K/Akt pathways
BackgroundMelanomas are caused by the malignant transformation of melanocytes. Numerous studies have demonstrated that the tyrosol components of salidroside inhibit tyrosinase activity. The PI3K/Akt/mTOR signaling pathway plays a crucial role in biological pigment synthesis. However, how salidroside...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1583580/full |
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| author | Qi Ouyang Qi Ouyang Shengye Tian Shengye Tian Hengyu Zhou Hengyu Zhou Ying Mao Xiang Li Feng Yan Feng Yan Ailong Liu Ailong Liu Xiang Hu Changqiao You Changqiao You Jun He |
| author_facet | Qi Ouyang Qi Ouyang Shengye Tian Shengye Tian Hengyu Zhou Hengyu Zhou Ying Mao Xiang Li Feng Yan Feng Yan Ailong Liu Ailong Liu Xiang Hu Changqiao You Changqiao You Jun He |
| author_sort | Qi Ouyang |
| collection | DOAJ |
| description | BackgroundMelanomas are caused by the malignant transformation of melanocytes. Numerous studies have demonstrated that the tyrosol components of salidroside inhibit tyrosinase activity. The PI3K/Akt/mTOR signaling pathway plays a crucial role in biological pigment synthesis. However, how salidroside achieves its anti-melanoma effect in melanoma by regulating PI3K/Akt/mTOR remains poorly understood. This study aimed to explore the effect of salidroside on PI3K/Akt/mTOR in melanoma, which plays a role in regulating melanogenesis.MethodsNetwork pharmacology was predicted that salidroside may exert an anti-melanoma effect through modulating melanin synthesis functions and signaling pathways. Zebrafish whole-embryo in situ hybridization, RT-qPCR, melanin synthesis and tumorigenesis assays, and were performed to investigate the therapeutic efficacy of salidroside in melanin synthesis. The mechanism of salidroside in anti-melanoma activity was examined by RT-qPCR, Western blot, immunofluorescence, in vivo imaging, immunohistochemistry.ResultsWe confirmed salidroside may exert an anti-melanoma effect through modulating melanin synthesis-related gene expression and PI3K/Akt pathway by Network pharmacology. Furthermore, salidroside slowed melanin synthesis in zebrafish embryos and H2O2-induced B16F10 cells by inhibited oxidative stress. Moreover, we determined the effect of salidroside on anti-melanin synthesis via PI3K/Akt/mTOR pathway in vitro, and western blot results showed that salidroside increased the expression of Nrf2 in the nucleus, as well as inhibited the phosphorylation of mTOR and PI3K/Akt pathway. Finally, intratumoral administration showed salidroside suppressed melanoma growth.ConclusionSalidroside inhibits melanin synthesis and melanoma development most likely by its antioxidant properties and downregulating the PI3K/Akt/mTOR pathway. Our results may provide a novel therapeutic strategy for the treatment of melanoma. |
| format | Article |
| id | doaj-art-d4e6c4a900a0492db9a969a74253dfe2 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-d4e6c4a900a0492db9a969a74253dfe22025-08-20T03:50:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.15835801583580Salidroside inhibits melanin synthesis and melanoma growth via mTOR and PI3K/Akt pathwaysQi Ouyang0Qi Ouyang1Shengye Tian2Shengye Tian3Hengyu Zhou4Hengyu Zhou5Ying Mao6Xiang Li7Feng Yan8Feng Yan9Ailong Liu10Ailong Liu11Xiang Hu12Changqiao You13Changqiao You14Jun He15Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Hunan Normal University, Changsha, ChinaThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Hunan Normal University, Changsha, ChinaThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Hunan Normal University, Changsha, ChinaThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, ChinaThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Hunan Normal University, Changsha, ChinaThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, ChinaHunan Provincial Engineering Technology Research Center of Stem Cell Exosome, Hunan Landfar Biotechnology Co. Ltd., Changsha, ChinaThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, ChinaHunan Provincial Engineering Technology Research Center of Stem Cell Exosome, Hunan Landfar Biotechnology Co. Ltd., Changsha, ChinaThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, ChinaThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, ChinaHunan Provincial Engineering Technology Research Center of Stem Cell Exosome, Hunan Landfar Biotechnology Co. Ltd., Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Hunan Normal University, Changsha, ChinaBackgroundMelanomas are caused by the malignant transformation of melanocytes. Numerous studies have demonstrated that the tyrosol components of salidroside inhibit tyrosinase activity. The PI3K/Akt/mTOR signaling pathway plays a crucial role in biological pigment synthesis. However, how salidroside achieves its anti-melanoma effect in melanoma by regulating PI3K/Akt/mTOR remains poorly understood. This study aimed to explore the effect of salidroside on PI3K/Akt/mTOR in melanoma, which plays a role in regulating melanogenesis.MethodsNetwork pharmacology was predicted that salidroside may exert an anti-melanoma effect through modulating melanin synthesis functions and signaling pathways. Zebrafish whole-embryo in situ hybridization, RT-qPCR, melanin synthesis and tumorigenesis assays, and were performed to investigate the therapeutic efficacy of salidroside in melanin synthesis. The mechanism of salidroside in anti-melanoma activity was examined by RT-qPCR, Western blot, immunofluorescence, in vivo imaging, immunohistochemistry.ResultsWe confirmed salidroside may exert an anti-melanoma effect through modulating melanin synthesis-related gene expression and PI3K/Akt pathway by Network pharmacology. Furthermore, salidroside slowed melanin synthesis in zebrafish embryos and H2O2-induced B16F10 cells by inhibited oxidative stress. Moreover, we determined the effect of salidroside on anti-melanin synthesis via PI3K/Akt/mTOR pathway in vitro, and western blot results showed that salidroside increased the expression of Nrf2 in the nucleus, as well as inhibited the phosphorylation of mTOR and PI3K/Akt pathway. Finally, intratumoral administration showed salidroside suppressed melanoma growth.ConclusionSalidroside inhibits melanin synthesis and melanoma development most likely by its antioxidant properties and downregulating the PI3K/Akt/mTOR pathway. Our results may provide a novel therapeutic strategy for the treatment of melanoma.https://www.frontiersin.org/articles/10.3389/fonc.2025.1583580/fullnetwork pharmacologysalidrosidemelanomaoxidative stressPI3K/Akt/mTOR pathway |
| spellingShingle | Qi Ouyang Qi Ouyang Shengye Tian Shengye Tian Hengyu Zhou Hengyu Zhou Ying Mao Xiang Li Feng Yan Feng Yan Ailong Liu Ailong Liu Xiang Hu Changqiao You Changqiao You Jun He Salidroside inhibits melanin synthesis and melanoma growth via mTOR and PI3K/Akt pathways Frontiers in Oncology network pharmacology salidroside melanoma oxidative stress PI3K/Akt/mTOR pathway |
| title | Salidroside inhibits melanin synthesis and melanoma growth via mTOR and PI3K/Akt pathways |
| title_full | Salidroside inhibits melanin synthesis and melanoma growth via mTOR and PI3K/Akt pathways |
| title_fullStr | Salidroside inhibits melanin synthesis and melanoma growth via mTOR and PI3K/Akt pathways |
| title_full_unstemmed | Salidroside inhibits melanin synthesis and melanoma growth via mTOR and PI3K/Akt pathways |
| title_short | Salidroside inhibits melanin synthesis and melanoma growth via mTOR and PI3K/Akt pathways |
| title_sort | salidroside inhibits melanin synthesis and melanoma growth via mtor and pi3k akt pathways |
| topic | network pharmacology salidroside melanoma oxidative stress PI3K/Akt/mTOR pathway |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1583580/full |
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