Targeting Skin Hyperpigmentation with Nature-Derived Tyrosinase Inhibitors: Sources, Mechanisms, and Translational Challenges
- 1College of Biological and Chemical Engineering, Qilu Institute of Technology, Jinan, Shandong, People’s Republic of China
- 2College of Biotechnology, Tianjin University of Science and Technology, Tianjin, People’s Republic of China
Abstract
Skin hyperpigmentation represents a highly prevalent dermatological issue that severely affects skin appearance and quality of life. Tyrosinase is well recognized as the critical rate-limiting enzyme in the melanin biosynthesis pathway, making it a prime target for skin-lightening interventions. Although synthetic depigmenting agents are widely used in cosmetics, their clinical applications are severely restricted by safety concerns, skin irritation, and chemical instability. In recent years, natural tyrosinase inhibitors originating from plants, fungi, marine organisms, and microbial metabolites have attracted extensive attention due to their promising efficacy, structural diversity, and multi-target activities, although long-term clinical and systemic safety data remain limited. This review comprehensively summarizes the molecular mechanisms underlying melanogenesis inhibition by natural compounds, their major biological sources, and representative active components, as well as key evidence from in vitro enzymatic assays, cellular models, and human clinical trials. We further discuss critical challenges in formulation development, including chemical instability, insufficient skin permeability, and safety considerations for long-term topical use. Finally, future research directions and translational opportunities are explored. By integrating recent advances and unresolved bottlenecks, this review aims to provide a scientific basis and rational guidance for the design and development of safe and effective natural-based skin-lightening products.
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BibTeX
@article{sun2026targeting,
title = {{Targeting Skin Hyperpigmentation with Nature-Derived Tyrosinase Inhibitors: Sources, Mechanisms, and Translational Challenges}},
author = {Zhe Sun and Yihui Li and Xuehui Wang and Rongxiao Wang and Wenjian Ma},
journal = {Clinical, Cosmetic and Investigational Dermatology},
year = {2026},
month = oct,
doi = {10.2147/ccid.s655765},
url = {https://doi.org/10.2147/ccid.s655765},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Targeting Skin Hyperpigmentation with Nature-Derived Tyrosinase Inhibitors: Sources, Mechanisms, and Translational Challenges
AU - Zhe Sun
AU - Yihui Li
AU - Xuehui Wang
AU - Rongxiao Wang
AU - Wenjian Ma
PY - 2026
DA - 2026/10/30
JO - Clinical, Cosmetic and Investigational Dermatology
DO - 10.2147/ccid.s655765
UR - https://doi.org/10.2147/ccid.s655765
AB - Skin hyperpigmentation represents a highly prevalent dermatological issue that severely affects skin appearance and quality of life. Tyrosinase is well recognized as the critical rate-limiting enzyme in the melanin biosynthesis pathway, making it a prime target for skin-lightening interventions. Although synthetic depigmenting agents are widely used in cosmetics, their clinical applications are severely restricted by safety concerns, skin irritation, and chemical instability. In recent years, natural tyrosinase inhibitors originating from plants, fungi, marine organisms, and microbial metabolites have attracted extensive attention due to their promising efficacy, structural diversity, and multi-target activities, although long-term clinical and systemic safety data remain limited. This review comprehensively summarizes the molecular mechanisms underlying melanogenesis inhibition by natural compounds, their major biological sources, and representative active components, as well as key evidence from in vitro enzymatic assays, cellular models, and human clinical trials. We further discuss critical challenges in formulation development, including chemical instability, insufficient skin permeability, and safety considerations for long-term topical use. Finally, future research directions and translational opportunities are explored. By integrating recent advances and unresolved bottlenecks, this review aims to provide a scientific basis and rational guidance for the design and development of safe and effective natural-based skin-lightening products.
SN - 1178-7015
ER -