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Article

Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)

by
Nurshafika Mohd Sakeh
1,
Nurliyana Najwa Md Razip
1,
Farah Idayu Mohd Ma’in
1,
Mohammad Nazri Abdul Bahari
1,
Naimah Latif
1,
Muhammad Nadeem Akhtar
2,
Zetty Norhana Balia Yusof
1 and
Syahida Ahmad
1,*
1
Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Serdang 43400, Selangor, Malaysia
2
Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, Gambang, Kuantan 26300, Pahang, Malaysia
*
Author to whom correspondence should be addressed.
Molecules 2020, 25(15), 3403; https://doi.org/10.3390/molecules25153403
Submission received: 19 May 2020 / Revised: 30 June 2020 / Accepted: 2 July 2020 / Published: 28 July 2020
(This article belongs to the Special Issue Pharmaceutical Development)
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Abstract

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 (Mitf) 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 Mitf which in turn down-regulate Tyr, Trp-1 and Trp-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.
Keywords: α-MSH; B16/F10 melanoma; chalcone; flavokawain; melanogenesis; zebrafish α-MSH; B16/F10 melanoma; chalcone; flavokawain; melanogenesis; zebrafish

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MDPI and ACS Style

Mohd Sakeh, N.; Md Razip, N.N.; Mohd Ma’in, F.I.; Abdul Bahari, M.N.; Latif, N.; Akhtar, M.N.; Balia Yusof, Z.N.; Ahmad, S. Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio). Molecules 2020, 25, 3403. https://doi.org/10.3390/molecules25153403

AMA Style

Mohd Sakeh N, Md Razip NN, Mohd Ma’in FI, Abdul Bahari MN, Latif N, Akhtar MN, Balia Yusof ZN, Ahmad S. Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio). Molecules. 2020; 25(15):3403. https://doi.org/10.3390/molecules25153403

Chicago/Turabian Style

Mohd Sakeh, Nurshafika, Nurliyana Najwa Md Razip, Farah Idayu Mohd Ma’in, Mohammad Nazri Abdul Bahari, Naimah Latif, Muhammad Nadeem Akhtar, Zetty Norhana Balia Yusof, and Syahida Ahmad. 2020. "Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)" Molecules 25, no. 15: 3403. https://doi.org/10.3390/molecules25153403

APA Style

Mohd Sakeh, N., Md Razip, N. N., Mohd Ma’in, F. I., Abdul Bahari, M. N., Latif, N., Akhtar, M. N., Balia Yusof, Z. N., & Ahmad, S. (2020). Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio). Molecules, 25(15), 3403. https://doi.org/10.3390/molecules25153403

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