Melanogenic Inhibition and toxicity assessment of flavokawain A and B on B16/F10 Melanoma Cells and zebrafish (Danio rerio)

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, c...

Full description

Bibliographic Details
Main Authors: Nurshafika, Mohd Sakeh, Nurliyana Najwa, Md Razip, Farah Idayu, Mohd Ma’in, Mohammad Nazri, Abdul Bahari, Naimah Mardhyyah, Latif, Muhammad Nadeem, Akhtar, Zetty Norhana, Balia Yusof, Syahida, Ahmad
Format: Article
Language:English
Published: MDPI - Open Access Publishing 2020
Subjects:
Online Access:https://umpir.ump.edu.my/id/eprint/29297/
_version_ 1848827274166534144
author Nurshafika, Mohd Sakeh
Nurliyana Najwa, Md Razip
Farah Idayu, Mohd Ma’in
Mohammad Nazri, Abdul Bahari
Naimah Mardhyyah, Latif
Muhammad Nadeem, Akhtar
Zetty Norhana, Balia Yusof
Syahida, Ahmad
author_facet Nurshafika, Mohd Sakeh
Nurliyana Najwa, Md Razip
Farah Idayu, Mohd Ma’in
Mohammad Nazri, Abdul Bahari
Naimah Mardhyyah, Latif
Muhammad Nadeem, Akhtar
Zetty Norhana, Balia Yusof
Syahida, Ahmad
author_sort Nurshafika, Mohd Sakeh
building UMP Institutional Repository
collection Online Access
description 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.
first_indexed 2025-11-15T03:58:06Z
format Article
id ump-29297
institution Universiti Malaysia Pahang
institution_category Local University
language English
last_indexed 2025-11-15T03:58:06Z
publishDate 2020
publisher MDPI - Open Access Publishing
recordtype eprints
repository_type Digital Repository
spelling ump-292972025-09-29T02:16:57Z https://umpir.ump.edu.my/id/eprint/29297/ Melanogenic Inhibition and toxicity assessment of flavokawain A and B on B16/F10 Melanoma Cells and zebrafish (Danio rerio) Nurshafika, Mohd Sakeh Nurliyana Najwa, Md Razip Farah Idayu, Mohd Ma’in Mohammad Nazri, Abdul Bahari Naimah Mardhyyah, Latif Muhammad Nadeem, Akhtar Zetty Norhana, Balia Yusof Syahida, Ahmad QP Physiology RA0421 Public health. Hygiene. Preventive Medicine RS Pharmacy and materia medica 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. MDPI - Open Access Publishing 2020 Article PeerReviewed pdf en cc_by_4 https://umpir.ump.edu.my/id/eprint/29297/1/11.%20Melanogenic%20Inhibition%20and%20Toxicity%20Assessment%20of%20Flavokawain%20A%20and%20B%20on%20B16F10.pdf Nurshafika, Mohd Sakeh and Nurliyana Najwa, Md Razip and Farah Idayu, Mohd Ma’in and Mohammad Nazri, Abdul Bahari and Naimah Mardhyyah, Latif and Muhammad Nadeem, Akhtar and 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 (15). pp. 1-18. ISSN 1420-3049 (print); 1420-3049 (online). (Published) https://doi.org/10.3390/molecules25153403 https://doi.org/10.3390/molecules25153403 https://doi.org/10.3390/molecules25153403
spellingShingle QP Physiology
RA0421 Public health. Hygiene. Preventive Medicine
RS Pharmacy and materia medica
Nurshafika, Mohd Sakeh
Nurliyana Najwa, Md Razip
Farah Idayu, Mohd Ma’in
Mohammad Nazri, Abdul Bahari
Naimah Mardhyyah, Latif
Muhammad Nadeem, Akhtar
Zetty Norhana, Balia Yusof
Syahida, Ahmad
Melanogenic Inhibition and toxicity assessment of flavokawain A and B on B16/F10 Melanoma Cells and zebrafish (Danio rerio)
title Melanogenic Inhibition and toxicity assessment of flavokawain A and B on B16/F10 Melanoma Cells and zebrafish (Danio rerio)
title_full Melanogenic Inhibition and toxicity assessment of flavokawain A and B on B16/F10 Melanoma Cells and zebrafish (Danio rerio)
title_fullStr Melanogenic Inhibition and toxicity assessment of flavokawain A and B on B16/F10 Melanoma Cells and zebrafish (Danio rerio)
title_full_unstemmed Melanogenic Inhibition and toxicity assessment of flavokawain A and B on B16/F10 Melanoma Cells and zebrafish (Danio rerio)
title_short Melanogenic Inhibition and toxicity assessment of flavokawain A and B on B16/F10 Melanoma Cells and zebrafish (Danio rerio)
title_sort melanogenic inhibition and toxicity assessment of flavokawain a and b on b16/f10 melanoma cells and zebrafish (danio rerio)
topic QP Physiology
RA0421 Public health. Hygiene. Preventive Medicine
RS Pharmacy and materia medica
url https://umpir.ump.edu.my/id/eprint/29297/
https://umpir.ump.edu.my/id/eprint/29297/
https://umpir.ump.edu.my/id/eprint/29297/