Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Serdang 43400, Selangor, Malaysia.
Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, Gambang, Kuantan 26300, Pahang, Malaysia.
Molecules. 2020 Jul 28;25(15):3403. doi: 10.3390/molecules25153403.
Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor () and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of which in turn down-regulate , -1 and -2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.
过量的黑色素生成暗示着色素沉着紊乱。已报道 flavokawain A (FLA) 和 flavokawain B (FLB) 具有抗黑色素生成活性，但它们对脊椎动物斑马鱼模型的黑色素生成抑制作用和毒性影响仍不清楚。在本研究中，评估了 FLA 和 FLB 对 α-MSH 诱导的 B16/F10 细胞中细胞黑色素含量和酪氨酸酶活性的细胞毒性和黑色素生成作用。通过定量实时 PCR (qPCR) 验证了小眼畸形相关转录因子 (MITF) 的主要调节因子和其他下游黑色素生成相关基因。还进一步观察了对斑马鱼模型的毒性评估和黑色素生成抑制作用。FLA 和 FLB 分别使 α-MSH 诱导的 B16/F10 细胞中的特定细胞黑色素含量显著减少了 4.3 倍和 9.6 倍。同时，FLA 使特定细胞酪氨酸酶活性显著降低了 7 倍，而 FLB 则降低了 9 倍。黑色素生成和酪氨酸酶活性的减少与 MITF 的 mRNA 抑制相关，这反过来又下调了 -1 和 -2。FLA 和 FLB 在 25 和 6.25 µM 时对斑马鱼模型均表现出非毒性作用。在斑马鱼模型上的进一步实验表明，FLA 和 FLB 在诱导黑色素生成下具有成功的表型去色素活性。总之，我们的研究结果为这两种查尔酮衍生物进一步作为有效的美白剂进行研究和开发提供了重要的第一步。
