ORIGINAL RESEARCH article
Front. Oncol.
Sec. Skin Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1583580
Salidroside inhibits melanin synthesis and melanoma growth via mTOR and PI3K/Akt pathways
Provisionally accepted
Qi Ouyang1,2
Shengye Tian1,2
Hengyu Zhou1,2Ying Mao1Xiang Li2Feng Yan1,3Ailong Liu1,3
Xiang Hu1*changqiao You1,3*Jun He2*- 1National and Local Joint Engineering Laboratory for Animal Peptide Drug Creation, Hunan Normal University, Changsha, Anhui Province, China
- 2Changsha Hospital for Maternal and Child Health Care,Hunan Normal University, Chang Sha, China
- 3Hunan Provincial Engineering Technology Research Center of Stem Cell Exosome, Hunan Landfar Biotechnology Co.Ltd., Changsha, China
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Background: Melanomas 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. Methods: Network pharmacology was predicted that salidroside may exert an anti-melanoma effect through modulating melanin synthesis functions and signaling pathways. Zebrafish whole-embryo in situ hybridisation, RT-qPCR, melanin synthesis and tumourigenesis 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. Results: We 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.Conclusion: Salidroside 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.
Keywords: Network Pharmacology, Salidroside, Melanoma, Oxidative Stress, PI3K/Akt/mTOR pathway
Received: 26 Feb 2025; Accepted: 13 Jun 2025.
Copyright: © 2025 Ouyang, Tian, Zhou, Mao, Li, Yan, Liu, Hu, You and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiang Hu, National and Local Joint Engineering Laboratory for Animal Peptide Drug Creation, Hunan Normal University, Changsha, 410081, Anhui Province, China
changqiao You, National and Local Joint Engineering Laboratory for Animal Peptide Drug Creation, Hunan Normal University, Changsha, 410081, Anhui Province, China
Jun He, Changsha Hospital for Maternal and Child Health Care,Hunan Normal University, Chang Sha, China
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