Chen H.-YKUAN-CHEN CHENGWang H.-THsieh C.-WLai Y.-J.2021-07-262021-07-26202114732130https://www.scopus.com/inward/record.uri?eid=2-s2.0-85096989251&doi=10.1111%2fjocd.13847&partnerID=40&md5=e13c6de29ee7841ace7c1c2fce7ccf4bhttps://scholars.lib.ntu.edu.tw/handle/123456789/572937Background: Ganoderma has been known as a cure for diseases since ancient times, and been used as a medicinal mushroom for more than 2000 years. By many accounts, Ganoderma lucidum extracts from fruit bodies exhibited the comparable tyrosinase inhibition activity. Aims: To validate A. cinnamomea mycelia anti-melanogenesis activity. Ethanolic extracts of A. cinnamomea mycelia were evaluated using in vitro cell-free tyrosinase assay, cell-based and zebrafish phenotype-based method. Meanwhile, safety assessment was also conducted to ensure the feasibility as the novel ingredients in cosmetic and pharmaceutic industries. Methods: The major regulatory enzymes being in charge of cutaneous pigmentation, was investigated in both cell-free and cellular enzyme systems, and in phenotype-based zebrafish model. A high-throughput TLC in vitro screening system was introduced to perform the initial evaluation of those with anti-melanin formation activity. Results: Among the fractions, 50% ethanol extracted fraction (AC_Et50_Hex) exhibited highest anti-melanin formation activity. AC_Et50_Hex (at 100 ppm) reduced 30% intracellular melanin of B16-F10 cells through suppression of tyrosinase activity and its protein expression. For animal study, not only does AC_Et50_Hex exhibited similar depigmenting efficacy to kojic acid (56.1% vs 52.3%) with lower dosage (50 ppm vs 1400 ppm), but showed less toxicity to zebrafish. Conclusion: A. cinnamomea mycelium extracts can be an ideal candidate/substitute for skin-whitening since kojic acid has been reported with carcinogenic effect. AC_Et50_Hex was recognized as a potential tyrosinase inhibitor throughout in vitro and in vivo analysis studies. The mass production of A. cinnamomea mycelium from agitated fermentation realizes the natural mushroom extracts for commercial application. ? 2020 Wiley Periodicals LLC[SDGs]SDG3journal article10.1111/jocd.13847332004692-s2.0-85096989251