Mutated Shiitake extracts inhibit melanin-producing neural crest-derived cells in zebrafish embryo

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology 2021-07, Vol.245, p.109033, Article 109033
• Main Authors: Mahmood, Ibrahim, Azfaralariff, Ahmad, Mohamad, Azhar, Airianah, Othman B., Law, Douglas, Dyari, Herryawan Ryadi Eziwar, Lim, Yi Chieh, Fazry, Shazrul
• Format: Article
• Language: English
• Subjects: Anticancer; Melagenosis; Pigmentation; Shiitake; Toxicity test; Zebrafish embryo
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2021.109033

The ability of natural extracts to inhibit melanocyte activity is of great interest to researchers. This study evaluates and explores the ability of mutated Shiitake (A37) and wildtype Shiitake (WE) extract to inhibit this activity. Several properties such as total phenolic (TPC) and total flavonoid content (TFC), antioxidant activity, effect on cell and component profiling were conducted. While having no significant differences in total phenolic content, mutation resulted in A37 having a TFC content (1.04 ± 0.7 mg/100 ml) compared to WE (0.86 ± 0.9 mg/100 ml). Despite that, A37 extract has lower antioxidant activity (EC50, A37 = 549.6 ± 2.70 μg/ml) than WE (EC50 = 52.8 ± 1.19 μg/ml). Toxicity tests on zebrafish embryos show that both extracts, stop the embryogenesis process when the concentration used exceeds 900 μg/ml. Although both extracts showed pigmentation reduction in zebrafish embryos, A37 extract showed no effect on embryo heartbeat. Cell cycle studies revealed that WE significantly affect the cell cycle while A37 not. Further tests found that these extracts inhibit the phosphorylation of Glycogen synthase kinase 3 β (pGSK3β) in HS27 cell line, which may explain the activation of apoptosis in melanin-producing cells. It was found that from 19 known compounds, 14 compounds were present in both WE and A37 extracts. Interestingly, the presence of decitabine in A37 extract makes it very potential for use in the medical application such as treatment of melanoma, skin therapy and even cancer. [Display omitted] •Wild (WE) and mutant (A37) shiitake extract were studied and characterized•While having higher flavonoid content, A37 extract have lower antioxidant activity.•Both extract effect the melagenosis and hatching process, but only A37 extract show no effect on heart rate.•Both extracts show no cytotoxic effect against HS-27.•A-37 extract show better apoptosis against A375.S2 cancer cells, and indifferent cell cycle profile compared to control.