Abstract
Flumequine is a well-known second generation quinolone antibiotic that induces phototoxicity. However, the effect of flumequine on skin melanogenesis is unclear. Therefore, we, for the first time, investigated whether flumequine regulates melanogenesis. The present study showed that flumequine slightly inhibited in vitro mushroom tyrosinase activity but significantly increased extracellular and intracellular melanin content in B16F10 cells and promoted the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. Additionally, flumequine remarkably increased melanin pigmentation in zebrafish larvae without any toxicity. We also found that flumequine stimulated p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation; inhibition of p38 MAPK and JNK resulted in significant downregulation of extracellular and intracellular melanin content in B16F10 cells and pigmentation of zebrafish larvae accompanied with suppression of MITF and tyrosinase expression, indicating that flumequine-mediated p38 and JNK promote melanogenesis in vitro and in vivo. According to the molecular docking prediction, flumequine targeted dual-specificity MAPK phosphatase 16 (DUSP16), which is a major negative regulator of p38 MAPK and JNK. Our findings demonstrate that flumequine induces an increase in melanin content in B16F10 cells and zebrafish larvae by activating p38 MAPK and JNK. These data show the potential of flumequine for use as an anti-vitiligo agent.
Highlights
Melanin is produced by melanocytes distributed in the basal layer of the epidermis, which is a key element of the skin, hair, and eye color [1]
Data based on many depigmenting small-molecule compounds verified that extracellular signal-regulated kinase (ERK) downregulates melanogenesis through proteasomal degradation of microphthalmia-associated transcription factor (MITF), thereby inhibiting melanogenesis; on the contrary, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) stimulates
SB203580 and SP600125 significantly attenuated flumequine-induced upregulation of extracellular flumequine-induced upregulation of extracellular and intracellular melanin and intracellular melanin content in B16F10 cells. These results indicate content in B16F10 cells. These results indicate that flumequine-mediated hypermelanogenesis is that flumequine-mediated hypermelanogenesis is positively regulated by the p38 MAPK and JNK
Summary
Melanin is produced by melanocytes distributed in the basal layer of the epidermis, which is a key element of the skin, hair, and eye color [1]. Melanin exerts beneficially protective effects against harmful ultraviolet (UV) radiation; excessive melanin production (hyperpigmentation) causes dermatological disorders such as freckles, age spots, and melisma [2]. In this regard, many attempts to discover medicinal flavonoids, and their derivatives and analogues that inhibit melanin biogenesis (melanogenesis), have been made over several decades [3,4]. Based on molecular docking analysis, Jadhav and Karuppayil showed that fluoroquinolones including flumequine form hydrogen bonds with active sites of human Topo IIa and Topo IIb, and could be a promising anti-cancer drug targeting Topo II [19]. Flumequine upregulated the activity and expression of melanogenic proteins such as tyrosinase and MITF by activating JNK and p38 MAPK, and molecular docking predicted that flumequine could interact with DUSP16
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
