Recent discovery of tyrosinase inhibitors in traditional Chinese medicines and screening methods

Ethnopharmacological relevance: Tyrosinase, the key rate-limiting enzyme for melanogenesis, is one of the main targets for skin senescence and some pigmented skin diseases, such as albinism and melanoma. Tyrosinase in-hibitors are capable of reducing melanin generation and deposition in the skin through blocking the reaction chain of formation. Thus, it has been used for anti-melanoma and showed the potential to be developed into novel skin whitening and spot removing products. With the trend of back-to-nature, natural tyrosinase inhibitors are receiving more and more attention. Traditional Chinese medicines (TCMs) as the promising source of novel chemotypes and pharmacophores, are huge treasures for the discovery of natural tyrosinase inhibitors charac-terized with green, safe, and highly efficient. Aim of this review: This review aims to provide a systematic overview of natural tyrosinase inhibitors and a detailed summary of the types of TCMs from which they originate. In addition, this paper also highlights the screening methods developed for exploring tyrosinase inhibitors in recent years, compares the advantages and disadvantages of various methods under the guidance of different screening principles, and predicts their ap-plications in the future. Materials and methods: Relevant literature have been obtained using the keywords "tyrosinase inhibitors", "traditional Chinese medicines", "whitening", and "screening" in scientific databases, such as "PubMed", "Sci-Finder", "Web of Science", "Elsevier", "China Knowledge Resource Integrated databases". Information was also collected from Chinese pharmacopoeia, Chinese herbal classics books, "Google Scholar", "Baidu Scholar", and other literature sources, etc. Results: An overview about the tyrosinase inhibitors derived from TCMs since 2002 has been compiled via the above-mentioned sources. Up to now, 186 components, mainly belonging to flavonoids, lignans, terpenoids, Diels-Alder adducts, simple phenylpropanoids and stilbenes, from 61 kinds of TCMs have been reported to possess tyrosinase inhibitory activity, among which flavonoids are mainly focused on. Furthermore, on the basis of bioactive detection strategies, the screening methods for tyrosinase inhibitors have been classified into bioaffinity-based, intrinsic enzymatic-based, and computer-aided drug design (CADD). Precisely because screening approaches are essential for rapid identification of tyrosinase inhibitors from TCMs, the principles, advantages and disadvantages, and specific applications of each method are presented along with a comparison of applicability. Conclusions: The summary of TCMs-derived inhibitors gives a clue on the discovery of candidates with the property to whiten the skin. Meanwhile, the outlook of developed screening methods provides technical refer-ences for the efficient exploration of safer and more effective tyrosinase inhibitors from TCMs.