Antimelanogenic activities of piperlongumine derived from Piper longum on murine B16F10 melanoma cells in vitro and zebrafish embryos in vivo: its molecular mode of depigmenting action

Abstract

In this study, the antimelanogenic activity of piperlongumine in murine B16F10 melanoma cells and zebrafish was investigated, and its mode of antimelanogenic action was elucidated using quantitative reverse transcription-polymerase chain reaction. A melanocyte-stimulating hormone (α-MSH, 200 nM) was used to induce melanin production in B16F10 melanoma cells, and kojic acid (200 μM) was used as a positive control. Piperlongumine had no inhibitory effects on cell growth at the treated concentrations (3 and 6 μM), and it significantly reduced total melanin production. Piperlongumine decreased the expression of Mitf, Tyr, Trp-1, and Trp-2 and tyrosinase activity was also dramatically reduced by the piper amide addition under α-MSH treatment. With these findings, zebrafish embryos were used to confirm antimelanogenic activity of piperlongumine, and it showed the potent antimelanogenic activity at the concentration of 1 μM. Altogether, piperlongumine has potent antimelanogenic activity, and these results support it as a candidate for natural depigmentation agent in a cosmetic and pharmaceutical industries.

Liquid-Liquid Chromatography Separation of Guaiane-Type Sesquiterpene Lactones from Ferula penninervis Regel & Schmalh. and Evaluation of Their In Vitro Cytotoxic and Melanin Inhibitory Potential

“…For instance, Mustapha et al [ 45 ] showed that both the ethyl acetate leaf extract of Crataegus azarolus L. (12.5 μg/mL) and one of its main constituents, vitexin-2ʺ- O -rhamnoside (5 μM), decreased the production of intracellular melanin in B16F10 cells by threefold as compared to untreated cells. Measuring the melanin content and release in B16F10 cells was also used to prove the anti-melanogenic activity of piperlongumine derived from Piper longum L. [ 48 ]. Piperlongumine (3 and 6 μM) had no inhibitory effects on the cell growth, but it significantly reduced the total melanin production by down-regulating the tyrosinase activity and expression of several pro-melanogenic proteins, such as tyrosinase-related protein-1 (TRP-1), TRP2, and microphthalmia-associated transcription factor (MITF) [ 48 ].…”

p-Hydroxybenzoic Acid β-d-Glucosyl Ester and Cimidahurinine with Antimelanogenesis and Antioxidant Effects from Pyracantha angustifolia via Bioactivity-Guided Fractionation

“…The demand for natural pigment reducers for pharmaceutical and cosmetic applications has increased rapidly [38,39]. Recently, natural products have been considered effective sources of…”

“…Although the primary role of melanin is the protection of skin tissue from UV irradiation, age spots and freckles can form as a result of the excessive production of melanin [3][4][5][6][7][8][9][10][11][12][13]. Considerable efforts have been made to develop products that reduce melanin synthesis for use as whitening constituents [23,29,[36][37][38][39][40][41][42]. TYR is an oxidase and is the rate-limiting enzyme in the production of melanin.…”

“…Fifteen compounds, four from the CHCl 3 fraction, one from the EtOAc fraction, and ten from the n-butanol fraction, were isolated and their chemical structures were determined (Figure 4). Among the fifteen phytochemicals, the anti-melanogenesis effects of the compounds are reported elsewhere, as representative whitening materials [36][37][38][39][40]. In the present study, seven compounds isolated from the n-butanol fraction were assessed.…”

“…Among the fifteen phytochemicals, the anti-melanogenesis effects of compounds 1-3, 5-7, 9, and 11 are reported elsewhere. In particular, arbutin, a representative whitening material, was used as a positive control in this study [36][37][38][39][40]. With the exception of these compounds, seven compounds isolated from the n-butanol fraction were assessed for their anti-melanogenesis and antioxidant effects.…”